V. Darras - Academia.edu (original) (raw)

Papers by V. Darras

Research paper thumbnail of Monocarboxylate Transporter 8 Modulates the Viability and Invasive Capacity of Human Placental Cells and Fetoplacental Growth in Mice

PLoS ONE, 2013

Monocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In h... more Monocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation, with increased expression in trophoblast cells from growth-restricted pregnancies. We postulate that MCT8 plays an important role in placental development and transplacental TH transport. We investigated the effect of altering MCT8 expression in human trophoblast in vitro and in a Mct8 knockout mouse model. Silencing of endogenous MCT8 reduced T3 uptake into human extravillous trophoblast-like cells (SGHPL-4; 40%, P,0.05) and primary cytotrophoblast (15%, P,0.05). MCT8 over-expression transiently increased T3 uptake (SGHPL-4:30%, P,0.05; cytotrophoblast: 15%, P,0.05). Silencing MCT8 did not significantly affect SGHPL-4 invasion, but with MCT8 over-expression T3 treatment promoted invasion compared with no T3 (3.3-fold; P,0.05). Furthermore, MCT8 silencing increased cytotrophoblast viability (,20%, P,0.05) and MCT8 over-expression reduced cytotrophoblast viability independently of T3 (,20%, P,0.05). In vivo, Mct8 knockout reduced fetal:placental weight ratios compared with wild-type controls at gestational day 18 (25%, P,0.05) but absolute fetal and placental weights were not significantly different. The volume fraction of the labyrinthine zone of the placenta, which facilitates maternal-fetal exchange, was reduced in Mct8 knockout placentae (10%, P,0.05). However, there was no effect on mouse placental cell proliferation in vivo. We conclude that MCT8 makes a significant contribution to T3 uptake into human trophoblast cells and has a role in modulating human trophoblast cell invasion and viability. In mice, Mct8 knockout has subtle effects upon fetoplacental growth and does not significantly affect placental cell viability probably due to compensatory mechanisms in vivo.

Research paper thumbnail of Thyroid Hormone Deiodinases during Embryonic Development of the Saltwater Crocodile (Crocodylus porosus)

General and Comparative Endocrinology, 2002

All tissues of the embryonic saltwater crocodile (Crocodylus porosus) gradually increased in weig... more All tissues of the embryonic saltwater crocodile (Crocodylus porosus) gradually increased in weight during development except for lung tissue, which had a peak weight of 1.09 g at day 67, thereafter decreasing in weight. The brain was a relatively large organ. Deiodinase activities in liver, kidney, lung, heart, gut, and brain from day 29 to day 77 of development of the saltwater crocodile were investigated. High-K(m) reverse triiodothyronine (rT(3)) outer ring deiodination (ORD) activity was present in all tissues except the brain. Activity ranged from 559 +/- 51.3 pmol rT(3) deiodinated/mg protein/min in the liver at day 77 to below 10 pmol rT(3) deiodinated/mg protein/min in gut, lung, and heart tissue. rT(3) ORD increased during development in the liver and kidney but decreased in the gut and lung. Activity in the heart was very low (less than 2 pmol rT(3) deiodinated/mg protein/min) and did not change during development. Low-K(m) thyroxine (T(4)) ORD in liver and kidney tissue had peaks of activity around day 49 of incubation (0.52 and 0.09 fmol T(4) deiodinated/mg protein/min, respectively). After day 49, T(4) ORD activity in these tissues decreased. T(4) ORD activity in gut, lung, and heart was very low (less than 0.04 fmol T(4) deiodinated/mg protein/min), with activity in lung increasing slightly during the rest of development. T(4) ORD activity in the brain increased toward day 77 (0.14 +/- 0.03 fmol T(4) deiodinated/mg protein/min), illustrating its importance in local triiodothyronine (T(3)) production during brain development. T(3) inner ring deiodination activity was present only in the embryonic liver and peaked at day 49 (10.1 fmol T(3) deiodinated/mg protein/min), after which activity decreased.

Research paper thumbnail of Changes in thyroid hormone levels in chicken liver during fasting and refeeding

Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 2002

In chickens, fasting results in increased plasma thyroxine (T(4)) levels and decreased plasma 3,5... more In chickens, fasting results in increased plasma thyroxine (T(4)) levels and decreased plasma 3,5,3'-triiodothyronine (T(3)) levels. Refeeding, in turn, restores normal plasma T(3) and T(4) levels. The liver is an important tissue for the regulation of circulating thyroid hormone levels. Previous studies demonstrated that the increase in hepatic type III deiodinase in fasted chickens plays a role in the decrease of plasma T(3). Another factor that could be important is the level of T(4) and T(3) uptake by the liver. In mammals, caloric restriction is known to diminish transport of T(4) and T(3) into tissues. The present study examines whether this is also the case in chicken. Four-week-old chickens were subjected to a 24-h starvation period followed by refeeding. Blood and liver samples were collected at the start of refeeding and at different times of refeeding. Thyroid hormone levels were measured directly in plasma and in tissues following extraction. The results demonstrate that intrahepatic T(4) levels are increased and T(3) levels are decreased in fasted compared to ad libitum fed chickens. The parallel changes in plasma and hepatic T(3) and T(4) content demonstrate that T(4) availability in liver tissue is not diminished during fasting, suggesting that in chicken thyroid hormone uptake by the liver is not affected by nutritional status.

Research paper thumbnail of Partial Food Restriction Increases Hepatic Inner Ring Deiodinating Activity in the Chicken and the Rat

General and Comparative Endocrinology, 1995

The effects of a long term partial food restriction were studied in chickens and rats. In chicken... more The effects of a long term partial food restriction were studied in chickens and rats. In chickens the treatment resulted in increased plasma T4 levels while T4 levels in rats remained unchanged. Plasma T3 decreased in both species. In vitro hepatic outer ring deiodinating type I (ORD-I) activity was not influenced by the food restriction, suggesting that the amount of ORD-I enzyme present in the liver remained unchanged. In vitro hepatic inner ring deiodinating type III activity, on the contrary, was greatly increased in both species. This increase may contribute to the decreased circulating T3 levels by increasing the degradation of T3 and diverting the deiodination of T4 to rT3 instead of to T3.

Research paper thumbnail of Changes in plasma T 3 during fasting/refeeding in tilapia (Oreochromis niloticus) are mainly regulated through changes in hepatic type II iodothyronine deiodinase

Fish Physiology and Biochemistry, 1998

Fasting and refeeding have considerable effects on thyroid hormone metabolism. In tilapia (Oreoch... more Fasting and refeeding have considerable effects on thyroid hormone metabolism. In tilapia (Oreochromis niloticus), fasting results in lower plasma T3 and T4 concentrations when compared to the ad libitum fed animals. This is accompanied by a decrease in hepatic type II (D2) and in brain and gill type III (D3) activity. No changes in kidney type I (D1) activity are

Research paper thumbnail of Thyroid hormone metabolism in poultry

Thyroid hormone (TH) receptors preferentially bind 3,5,3'-triiodothyronine (T 3 ). Therefore the ... more Thyroid hormone (TH) receptors preferentially bind 3,5,3'-triiodothyronine (T 3 ). Therefore the metabolism of thyroxine (T 4 ) secreted by the thyroid gland in peripheral tissues, resulting in the production and degradation of receptor-active T 3 , plays a major role in thyroid function. The most important metabolic pathway for THs is deiodination. Another important pathway is sulfation, which is a reversible pathway that has been shown to interact with TH deiodination efficiency. The enzymes catalysing TH deiodination consist of three types. Type I deiodinase (D1) catalyses both outer ring (ORD) and inner ring deiodination (IRD). Type II deiodinase (D2) only catalyses ORD while type III (D3) only catalyses IRD. The three chicken deiodinase cDNAs have been cloned recently. These enzymes all belong to the family of selenoproteins. Ontogenetic studies show that the availability of deiodinases is regulated in a tissue specific and developmental stage dependent way. Characteristic for the chicken is the presence of very high levels of T 3 inactivating D3 enzyme in the embryonic liver. Hepatic D3 is subject to acute regulation in a number of situations. Both growth hormone and glucocorticoid injection rapidly decrease hepatic D3 levels, hereby increasing plasma T 3 without affecting hepatic D1 levels. The inhibition of D3 seems to be regulated mainly at the level of D3 gene transcription. The effect of growth hormone on D3 expression persists throughout life, while glucocorticoids start to inhibit hepatic D1 expression in posthatch chickens. Food restriction in growing chickens increases hepatic D3 levels. This contributes to the decrease in plasma T 3 necessary to reduce energy loss. Refeeding restores hepatic D3 and plasma T 3 to control levels within a few hours. It can be concluded that the tissue and time dependent regulation of the balance between TH activating and inactivating enzymes plays an essential role in the control of local T 3 availability and hence in TH activity.

Research paper thumbnail of Corticosterone-induced negative feedback mechanisms within the hypothalamo-pituitary-adrenal axis of the chicken

Journal of Endocrinology, 2005

This paper reports the results of in vivo and in vitro experiments on the feedback effects of cor... more This paper reports the results of in vivo and in vitro experiments on the feedback effects of corticosterone on the hypothalamo-pituitary-adrenal axis in embryos at day 18 of incubation and in 9-day-old chickens. In vivo, a significant negative feedback was detected on the levels of corticotropin-releasing factor (CRF) precursor (proCRF) mRNA and on the plasma concentration of corticosterone, two hours after a single intravenous injection with 40 µg corticosterone. In contrast, the levels of CRF peptide in the hypothalamic area, the CRF receptor type 1 (CRF-R1) mRNA and pro-opiomelanocortin (POMC) mRNA levels in the pituitary were not affected by the in vivo administration of corticosterone. In vitro, incubation with 1 µM corticosterone did not affect the CRF-R1 mRNA levels in the pituitary, but significant feedback inhibition was observed on the POMC mRNA levels. These in vitro effects were the same at the two ages studied. The in vitro feedback effect on the proCRF gene expression, however, differed with age. In 9-day-old animals a decrease in gene expression was observed which was not detectable in embryonic tissue at day 18 of the ontogeny.

Research paper thumbnail of Control of Peripheral Thyroid Hormone Levels by Activating and Inactivating Deiodinases

Annals of the New York Academy of Sciences, 1998

The main secretion product of the vertebrate thyroid gland is thyroxine or T 4. However, it is we... more The main secretion product of the vertebrate thyroid gland is thyroxine or T 4. However, it is well known that thyroid hormone receptors have a much higher affinity for 3, 5, 3′-triiodothyronine (T 3), which is considered to be the active thyroid hormone. This activation ...

Research paper thumbnail of Comparative study of iodothyronine outer ring and inner ring deiodinase activities in five teleostean fishes

Fish Physiology and …, 1998

The presence of outer ring deiodinating (ORD) and inner ring deiodinating (IRD) activities was in... more The presence of outer ring deiodinating (ORD) and inner ring deiodinating (IRD) activities was investigated in different tissues of Oreochromis niloticus (Nile tilapia), Clarias gariepinus (African catfish), Oncorhynchus mykiss (rainbow trout) and Scophthalmus maximus (turbot). High-K m rT 3 ORD is present in the kidney of most of the fishes studied, except in catfish. In turbot, besides the kidney, rT 3 ORD is also present in liver, heart and ovary. Low-K m T 4 ORD is found in the liver and low-K m T 3 IRD in the brain of all the fishes studied. In addition, low levels of low-K m T 3 IRD were demonstrated in gill and skin of Nile tilapia, liver of rainbow trout and gill and kidney of turbot. For the different teleosts, the biochemical properties of the different rT 3 -deiodinating enzymes mentioned, T 4 ORD in liver and T 3 IRD in brain and tilapia gill were compared to those of the deiodinases formerly characterized in Oreochromis aureus (blue tilapia).

Research paper thumbnail of Distribution and regulation of chicken growth hormone secretagogue receptor isoforms

General and Comparative Endocrinology, 2003

Chicken ghrelin has recently been isolated as a hormone which stimulates growth hormone and corti... more Chicken ghrelin has recently been isolated as a hormone which stimulates growth hormone and corticosterone secretion in chicken. Ghrelin mediates these actions in mammals by binding to the growth hormone secretagogue receptor (GHS-R). In this study, we describe the partial cloning of two chicken GHS-R (cGHS-R) isoforms: cGHS-R1a and cGHS-R1c. cGHS-R1a and cGHS-R1c cDNA show, respectively, 81 and 78% homology with the corresponding parts of the human GHS-R1a cDNA. In contrast to the human GHS-R1b isoform, which is truncated after transmembrane domain 5 (TM-5), the chicken GHS-R1c isoform lacks 16 amino acids in TM-6 suggesting that this isoform is not active in ghrelin signal transduction. The cystein residues, N-linked glycosylation sites and potential phosphorylation sites, found in the human GHS-R1a, were also conserved in both chicken isoforms. RT-PCR analysis demonstrated cGHS-R1a and cGHS-R1c mRNA expression in all tissues tested, except liver and pancreas, with highest levels in the pituitary and the hypothalamus. Intermediate levels of expression were detected, in descending order, in the ovary, telencephalon, heart, adrenal gland, cerebellum, and optic lobes whereas low expression was detected in the brainstem, lung, kidney, proventriculus, duodenum, and colon. Very low expression was found in skin, stomach, and muscle. cGHS-R1c was expressed in lower amounts than cGHS-R1a in all analysed tissues. Administration of 1 lM chicken ghrelin to pituitaries in vitro resulted in a down-regulation of both cGHS-R isoforms within 15 min, whereas after 1 h levels returned to control values. Growth hormone and corticosterone down-regulated cGHS-R1a and cGHS-R1c mRNA expression within 60 min of exposure, whereas growth hormone-releasing factor 1-29 (1 lM) only reduced cGHS-R1a mRNA expression after 60 min. Thyrotropin-releasing hormone (1 lM) did not alter cGHS-R expression.

Research paper thumbnail of Effects of experimental hypo- and hyperthyroidism on iodothyronine deiodinases in Nile tilapia, Oreochromis niloticus

Fish Physiology and Biochemistry, 1999

In the present study, we examined the effects of experimentally-induced increases or decreases in... more In the present study, we examined the effects of experimentally-induced increases or decreases in plasma concentrations of thyroid hormones on iodothyronine deiodinases in tilapia, Oreochromis niloticus. To obtain hyperthyroid tilapia, fish were injected with porcine follicle stimulating hormone (pFSH) 36 hours before sampling or fed on demand for 11 days with tilapia pellets containing 12 ppm T3. Tilapias were made

Research paper thumbnail of Transcriptional regulation of iodothyronine deiodinases during embryonic development

Molecular and Cellular Endocrinology, 2001

A single dose of chicken growth hormone (cGH) or dexamethasone acutely increases circulating T(3)... more A single dose of chicken growth hormone (cGH) or dexamethasone acutely increases circulating T(3) levels in 18-day-old chicken embryos through a reduction of hepatic type III iodothyronine deiodinase (D3). The data in the present study suggest that this decrease in D3 is induced by a direct downregulation of hepatic D3 gene transcription. The lack of effect of cGH or dexamethasone on brain and kidney D3 activity, furthermore suggests that both hormones affect peripheral thyroid hormone metabolism in a tissue specific manner. Dexamethasone administration also results in an increase in brain type II iodothyronine deiodinase (D2) activity and mRNA levels that is also regulated at a transcriptional level. In contrast, however, cGH has no effect on brain D2 activity, thereby suggesting that either GH cannot pass through the blood-brain barrier in chicken or that cGH and dexamethasone regulate thyroid hormone deiodination by different mechanisms. In addition, the very short half-life of D2 and D3 (t(1/2)<1 h) in comparison with the longer half life of type I iodothyronine deiodinase (D1, t(1/2)>8 h), allows for D2 and D3 to play a more prominent role in the acute regulation of peripheral thyroid hormone metabolism than D1.

Research paper thumbnail of Thyroid Hormone Sulfation in Chicken and Axolotl

Netherlands Journal of Zoology - NETH J ZOOL, 2000

ABSTRACT

Research paper thumbnail of Inhibition and activation of the thyroidal axis by the adrenal axis in vertebrates

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 1998

Hormones of the adrenal or interrenal axis and stress situations which induce elevated glucocorti... more Hormones of the adrenal or interrenal axis and stress situations which induce elevated glucocorticoid plasma levels (e.g. handling and starvation), inhibit thyroid function in growing and adult vertebrates. However, data indicate that during foetal and embryonic development (mammals and birds) or during larval growth and metamorphosis (fish and amphibians), the adrenal axis may stimulate thyroid function. Recent findings have provided some information concerning this stimulatory interference of the adrenal axis. In amphibians corticotropin releasing hormone and not thyrotropin releasing hormone is thyrotropic during metamorphosis, thus providing the substrate T4 necessary for T3 production. Other data indicate that the increase in plasma T3 at metamorphic climax may be the result of an inhibition of the T3 degrading activity, rather than stimulation of the T4 into T3 converting activity, and that glucocorticoids may be responsible for this. Also, in the chick embryo glucocorticoids effectively increase plasma T3 concentration by reducing the hepatic T3 degrading activity, whereas corticotropin releasing hormone also induces an elevation in the thyrotropin plasma levels and hence raises T4 concentrations which may function as a substrate for T3 production.

Research paper thumbnail of Identification of somatostatin receptors controlling growth hormone and thyrotropin secretion in the chicken using receptor subtype-specific agonists

Journal of Endocrinology, 2003

Somatostatin (SRIH) functions as an endocrine mediator in processes such as growth, immune resist... more Somatostatin (SRIH) functions as an endocrine mediator in processes such as growth, immune resistance and reproduction. Five SRIH receptors (sstr1-5) have been identified in mammals, where they are expressed in both the brain and peripheral tissues. To study the specific function of each receptor subtype, specific agonists (ag1-5) have been synthesized. The high degree of homology between mammalian and avian SRIH receptors suggests that these agonists might also be used in chickens. In this paper we describe two in vitro protocols (static incubation and perifusion system) to identify the SRIH receptors controlling the secretion of GH and TSH from the chicken pituitary. We found that basal GH or TSH secretion were never affected when SRIH or an agonist (1 µM) were added. SRIH diminished the GH as well as the TSH response to TSH-releasing hormone (TRH; 100 nM) in both systems. Our results have indicated that the SRIH actions at the level of the pituitary are regulated through specific receptor subtypes. In both the static and flow incubations, ag2 lowered the GH response to TRH, whereas stimulated TSH release was diminished by both ag2 and ag5. Ag3 and ag4 tended to increase rather than decrease the responsiveness of both pituitary cell types to TRH in perifusion studies. Our data have indicated that SRIH inhibits chicken pituitary function through sstr2 and sstr5. Only sstr2 seems to be involved in the control of chicken GH release, whereas both sstr2 and sstr5 inhibit induced GH secretion in mammals. The possible stimulatory action of ag3 and ag4 may point towards a species-specific function of sstr3 and sstr4. of chicken hypophyseal thyrotropes and development of a radioimmunological indicator for chicken TSH using monoclonal and polyclonal homologous antibodies in a subtractive strategy. General and Comparative Endocrinology 92 189-200.

Research paper thumbnail of Low submetamorphic doses of dexamethasone and thyroxine induce complete metamorphosis in the axolotl (Ambystoma mexicanum) when injected together

General and Comparative Endocrinology, 2004

Entanglement of functions between the adrenal (or interrenal) and thyroid axis has been well desc... more Entanglement of functions between the adrenal (or interrenal) and thyroid axis has been well described for all vertebrates and can be tracked down up to the level of gene expression. Both thyroid hormones and corticosteroids may induce morphological changes leading to metamorphosis climax in the neotenic Mexican axolotl (Ambystoma mexicanum). In a first series of experiments, metamorphosis was induced with an injection of 25 lg T 4 on three alternate days as judged by a decrease in body weight and tail height together with complete gill resorption. This injection also resulted in elevated plasma concentrations of T 3 and corticosterone. Previous results have indicated that the same dose of dexamethasone (DEX) is ineffective in this regard (Gen. Comp. Endocrinol. 127 (2002) 157). In a second series of experiments low doses of T 4 (0.5 lg) or DEX (5 lg) were ineffective to induce morphological changes. However, when these submetamorphic doses were injected together, morphological changes were observed within one week leading to complete metamorphosis. It is concluded that thyroid hormones combined with corticosteroids are essential for metamorphosis in the axolotl and that only high doses of either thyroid hormone or corticosteroid can induce morphological changes when injected separately.

Research paper thumbnail of Effect of the sex-linked dwarf gene on thyrotrophic and somatotrophic axes in the chick embryo

Plasma concentrations of thyroxine (T4), triiodothyronine (T3), reversed triiodothyronine (rT3), ... more Plasma concentrations of thyroxine (T4), triiodothyronine (T3), reversed triiodothyronine (rT3), and insulin-like growth factors I and II (IGF-I, IGF-II) together with peripheral 5'-monodeiodination activity were measured in both normal and sex-linked dwarf embryos between day 14 of incubation and day 1 posthatch. Plasma T4 levels increased gradually during embryonic development while T3 concentrations remained low until day 20, when a sharp increase was observed. rT3 levels also increased from day 14 and dropped on day 20 when T3 levels started to increase. 5'-monodeiodination activity was high on day 14 of incubation, decreased thereafter, and showed an increase at the time of air sac penetration together with increased T3 levels. At this stage, differences between normal and dwarf embryos were observed; the latter had lower nonsignificant 5'-Monodeiodination activity and lower (P less than 0.01) plasma T3 levels. Plasma IGF-II levels were high during the whole embryonic period studied. Dwarf embryos had lower (P less than 0.05) IGF-II levels at the time of hatching. IGF-I levels were high on days 14 and 16, declined afterwards, and started to increase again around hatching. With the exception of T3 and IGF-II levels, introduction of the dwarf gene did not cause major changes in the hormonal parameters studied. This may explain the identical body weight at hatching.

Research paper thumbnail of Hypothalamic hormones that release growth hormone stimulate hepatic 5'-monodeiodination activity in the chick embryo

Journal of Endocrinology, 1988

Plasma GH, tri-iodothyronine (T3), thyroxine (T4) and liver 5'-monodeiodination (5&#3... more Plasma GH, tri-iodothyronine (T3), thyroxine (T4) and liver 5'-monodeiodination (5'-D) activity were measured in 18-day-old chick embryos injected with thyrotrophin-releasing hormone (TRH) and human pancreatic growth hormone releasing factor (hpGRF). Injections of 0.1 and 1 microgram TRH and 1.5 micrograms hpGRF increased the concentration of plasma GH while injection of 15 micrograms hpGRF had no effect. Concentrations of plasma T3 were raised after injection of TRH or hpGRF. Injections of TRH but not of hpGRF raised the concentration of plasma T4. The increases in concentration of plasma T3 after injection of TRH or hpGRF were parallelled by increases in liver 5'-D activity. An injection of 0.25 micrograms T4 significantly raised the concentration of T4 in plasma but had no effect on plasma T3 or liver 5'-D activity. It is concluded that the release of chicken GH by TRH or hpGRF is responsible for the observed increase in plasma concentration of T3 and liver 5'-D activity.

Research paper thumbnail of Regulation of Thyroid Hormone Metabolism during Fasting and Refeeding in Chicken

General and Comparative Endocrinology, 1999

Fasting and refeeding have considerable effects on thyroid hormone metabolism. In the present stu... more Fasting and refeeding have considerable effects on thyroid hormone metabolism. In the present study, 8-day-old meat-type cockerels were subjected to a 2-day starvation period followed by 3 days' refeeding. Blood and tissue samples were collected at the start of the experiment, at 4, 24, and 48 h of starvation, and at 4, 8, 24, 48, and 72 h of refeeding. This study demonstrates that in chicken, fasting decreased plasma T(3) and TSH levels and increased plasma T(4) concentrations. This was accompanied by increased hepatic type III deiodinase (D3) and decreased renal D3 activity. There were no changes in hepatic or renal type I deiodinase (D1). Refeeding restored normal plasma T(3), T(4), and TSH levels, while hepatic D3 and renal D3 activities returned to prefasting levels. Again hepatic D1 was not affected, but renal D1 was lower than the ad libitum values during the entire refeeding period. These results confirm that liver D3 is involved in the regulation of plasma T(3) during fasting and refeeding in the chicken. Northern blot analysis demonstrated increased hepatic D3 mRNA levels during the first day of starvation that disappeared by the end of the second day; refeeding had no additional effects. These results suggest that in fasted chickens the rapid upregulation of hepatic D3 occurs predominantly at a pretranslational level, whereas the drop in hepatic D3 activity after refeeding is probably regulated at a posttranslational level. In addition, renal D3 may play a role in the regulation of local T(3) availability.

Research paper thumbnail of Differential expression of iodothyronine deiodinases in chicken tissues during the last week of embryonic development

General and Comparative Endocrinology, 2002

In the current study, the authors examined the type 1 (D1), type 2 (D2), and type 3 deiodinase (D... more In the current study, the authors examined the type 1 (D1), type 2 (D2), and type 3 deiodinase (D3) activity and mRNA expression patterns in thyroid, lung, brain, pituitary, heart, liver, spleen, gonads, skin, muscle, intestine, Fabricius' bursa, and kidney during the last week of chicken embryonic development and the first 2 days posthatch. The D3 was the most widely expressed, occurring in all examined tissues. Also, the D1 knows a widespread distribution, although no D1 activity or mRNA expression could be detected in the brain, the thyroid, the muscle, and the skin. In contrast, the D2 has a much more restricted expression pattern, since the brain is the only organ where, prior to hatching, both in vitro D2 activity and D2 mRNA expression can be detected. Taken together, these results demonstrate that during the last week of chicken embryonic development, the majority of tissues express D3, together with either D1 or D2, indicating that each tissue possesses the necessary tools to regulate local thyroid hormone levels at least partly independent from T(3) and T(4) levels in plasma. In addition, the deiodinase expression data could be correlated to certain thyroid hormone dependent tissue-specific developmental events. This strongly suggests that in birds, as in mammals and amphibians, the correct spatial and temporal expression of iodothyronine deiodinases are essential for normal embryonic development.

Research paper thumbnail of Monocarboxylate Transporter 8 Modulates the Viability and Invasive Capacity of Human Placental Cells and Fetoplacental Growth in Mice

PLoS ONE, 2013

Monocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In h... more Monocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation, with increased expression in trophoblast cells from growth-restricted pregnancies. We postulate that MCT8 plays an important role in placental development and transplacental TH transport. We investigated the effect of altering MCT8 expression in human trophoblast in vitro and in a Mct8 knockout mouse model. Silencing of endogenous MCT8 reduced T3 uptake into human extravillous trophoblast-like cells (SGHPL-4; 40%, P,0.05) and primary cytotrophoblast (15%, P,0.05). MCT8 over-expression transiently increased T3 uptake (SGHPL-4:30%, P,0.05; cytotrophoblast: 15%, P,0.05). Silencing MCT8 did not significantly affect SGHPL-4 invasion, but with MCT8 over-expression T3 treatment promoted invasion compared with no T3 (3.3-fold; P,0.05). Furthermore, MCT8 silencing increased cytotrophoblast viability (,20%, P,0.05) and MCT8 over-expression reduced cytotrophoblast viability independently of T3 (,20%, P,0.05). In vivo, Mct8 knockout reduced fetal:placental weight ratios compared with wild-type controls at gestational day 18 (25%, P,0.05) but absolute fetal and placental weights were not significantly different. The volume fraction of the labyrinthine zone of the placenta, which facilitates maternal-fetal exchange, was reduced in Mct8 knockout placentae (10%, P,0.05). However, there was no effect on mouse placental cell proliferation in vivo. We conclude that MCT8 makes a significant contribution to T3 uptake into human trophoblast cells and has a role in modulating human trophoblast cell invasion and viability. In mice, Mct8 knockout has subtle effects upon fetoplacental growth and does not significantly affect placental cell viability probably due to compensatory mechanisms in vivo.

Research paper thumbnail of Thyroid Hormone Deiodinases during Embryonic Development of the Saltwater Crocodile (Crocodylus porosus)

General and Comparative Endocrinology, 2002

All tissues of the embryonic saltwater crocodile (Crocodylus porosus) gradually increased in weig... more All tissues of the embryonic saltwater crocodile (Crocodylus porosus) gradually increased in weight during development except for lung tissue, which had a peak weight of 1.09 g at day 67, thereafter decreasing in weight. The brain was a relatively large organ. Deiodinase activities in liver, kidney, lung, heart, gut, and brain from day 29 to day 77 of development of the saltwater crocodile were investigated. High-K(m) reverse triiodothyronine (rT(3)) outer ring deiodination (ORD) activity was present in all tissues except the brain. Activity ranged from 559 +/- 51.3 pmol rT(3) deiodinated/mg protein/min in the liver at day 77 to below 10 pmol rT(3) deiodinated/mg protein/min in gut, lung, and heart tissue. rT(3) ORD increased during development in the liver and kidney but decreased in the gut and lung. Activity in the heart was very low (less than 2 pmol rT(3) deiodinated/mg protein/min) and did not change during development. Low-K(m) thyroxine (T(4)) ORD in liver and kidney tissue had peaks of activity around day 49 of incubation (0.52 and 0.09 fmol T(4) deiodinated/mg protein/min, respectively). After day 49, T(4) ORD activity in these tissues decreased. T(4) ORD activity in gut, lung, and heart was very low (less than 0.04 fmol T(4) deiodinated/mg protein/min), with activity in lung increasing slightly during the rest of development. T(4) ORD activity in the brain increased toward day 77 (0.14 +/- 0.03 fmol T(4) deiodinated/mg protein/min), illustrating its importance in local triiodothyronine (T(3)) production during brain development. T(3) inner ring deiodination activity was present only in the embryonic liver and peaked at day 49 (10.1 fmol T(3) deiodinated/mg protein/min), after which activity decreased.

Research paper thumbnail of Changes in thyroid hormone levels in chicken liver during fasting and refeeding

Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 2002

In chickens, fasting results in increased plasma thyroxine (T(4)) levels and decreased plasma 3,5... more In chickens, fasting results in increased plasma thyroxine (T(4)) levels and decreased plasma 3,5,3'-triiodothyronine (T(3)) levels. Refeeding, in turn, restores normal plasma T(3) and T(4) levels. The liver is an important tissue for the regulation of circulating thyroid hormone levels. Previous studies demonstrated that the increase in hepatic type III deiodinase in fasted chickens plays a role in the decrease of plasma T(3). Another factor that could be important is the level of T(4) and T(3) uptake by the liver. In mammals, caloric restriction is known to diminish transport of T(4) and T(3) into tissues. The present study examines whether this is also the case in chicken. Four-week-old chickens were subjected to a 24-h starvation period followed by refeeding. Blood and liver samples were collected at the start of refeeding and at different times of refeeding. Thyroid hormone levels were measured directly in plasma and in tissues following extraction. The results demonstrate that intrahepatic T(4) levels are increased and T(3) levels are decreased in fasted compared to ad libitum fed chickens. The parallel changes in plasma and hepatic T(3) and T(4) content demonstrate that T(4) availability in liver tissue is not diminished during fasting, suggesting that in chicken thyroid hormone uptake by the liver is not affected by nutritional status.

Research paper thumbnail of Partial Food Restriction Increases Hepatic Inner Ring Deiodinating Activity in the Chicken and the Rat

General and Comparative Endocrinology, 1995

The effects of a long term partial food restriction were studied in chickens and rats. In chicken... more The effects of a long term partial food restriction were studied in chickens and rats. In chickens the treatment resulted in increased plasma T4 levels while T4 levels in rats remained unchanged. Plasma T3 decreased in both species. In vitro hepatic outer ring deiodinating type I (ORD-I) activity was not influenced by the food restriction, suggesting that the amount of ORD-I enzyme present in the liver remained unchanged. In vitro hepatic inner ring deiodinating type III activity, on the contrary, was greatly increased in both species. This increase may contribute to the decreased circulating T3 levels by increasing the degradation of T3 and diverting the deiodination of T4 to rT3 instead of to T3.

Research paper thumbnail of Changes in plasma T 3 during fasting/refeeding in tilapia (Oreochromis niloticus) are mainly regulated through changes in hepatic type II iodothyronine deiodinase

Fish Physiology and Biochemistry, 1998

Fasting and refeeding have considerable effects on thyroid hormone metabolism. In tilapia (Oreoch... more Fasting and refeeding have considerable effects on thyroid hormone metabolism. In tilapia (Oreochromis niloticus), fasting results in lower plasma T3 and T4 concentrations when compared to the ad libitum fed animals. This is accompanied by a decrease in hepatic type II (D2) and in brain and gill type III (D3) activity. No changes in kidney type I (D1) activity are

Research paper thumbnail of Thyroid hormone metabolism in poultry

Thyroid hormone (TH) receptors preferentially bind 3,5,3'-triiodothyronine (T 3 ). Therefore the ... more Thyroid hormone (TH) receptors preferentially bind 3,5,3'-triiodothyronine (T 3 ). Therefore the metabolism of thyroxine (T 4 ) secreted by the thyroid gland in peripheral tissues, resulting in the production and degradation of receptor-active T 3 , plays a major role in thyroid function. The most important metabolic pathway for THs is deiodination. Another important pathway is sulfation, which is a reversible pathway that has been shown to interact with TH deiodination efficiency. The enzymes catalysing TH deiodination consist of three types. Type I deiodinase (D1) catalyses both outer ring (ORD) and inner ring deiodination (IRD). Type II deiodinase (D2) only catalyses ORD while type III (D3) only catalyses IRD. The three chicken deiodinase cDNAs have been cloned recently. These enzymes all belong to the family of selenoproteins. Ontogenetic studies show that the availability of deiodinases is regulated in a tissue specific and developmental stage dependent way. Characteristic for the chicken is the presence of very high levels of T 3 inactivating D3 enzyme in the embryonic liver. Hepatic D3 is subject to acute regulation in a number of situations. Both growth hormone and glucocorticoid injection rapidly decrease hepatic D3 levels, hereby increasing plasma T 3 without affecting hepatic D1 levels. The inhibition of D3 seems to be regulated mainly at the level of D3 gene transcription. The effect of growth hormone on D3 expression persists throughout life, while glucocorticoids start to inhibit hepatic D1 expression in posthatch chickens. Food restriction in growing chickens increases hepatic D3 levels. This contributes to the decrease in plasma T 3 necessary to reduce energy loss. Refeeding restores hepatic D3 and plasma T 3 to control levels within a few hours. It can be concluded that the tissue and time dependent regulation of the balance between TH activating and inactivating enzymes plays an essential role in the control of local T 3 availability and hence in TH activity.

Research paper thumbnail of Corticosterone-induced negative feedback mechanisms within the hypothalamo-pituitary-adrenal axis of the chicken

Journal of Endocrinology, 2005

This paper reports the results of in vivo and in vitro experiments on the feedback effects of cor... more This paper reports the results of in vivo and in vitro experiments on the feedback effects of corticosterone on the hypothalamo-pituitary-adrenal axis in embryos at day 18 of incubation and in 9-day-old chickens. In vivo, a significant negative feedback was detected on the levels of corticotropin-releasing factor (CRF) precursor (proCRF) mRNA and on the plasma concentration of corticosterone, two hours after a single intravenous injection with 40 µg corticosterone. In contrast, the levels of CRF peptide in the hypothalamic area, the CRF receptor type 1 (CRF-R1) mRNA and pro-opiomelanocortin (POMC) mRNA levels in the pituitary were not affected by the in vivo administration of corticosterone. In vitro, incubation with 1 µM corticosterone did not affect the CRF-R1 mRNA levels in the pituitary, but significant feedback inhibition was observed on the POMC mRNA levels. These in vitro effects were the same at the two ages studied. The in vitro feedback effect on the proCRF gene expression, however, differed with age. In 9-day-old animals a decrease in gene expression was observed which was not detectable in embryonic tissue at day 18 of the ontogeny.

Research paper thumbnail of Control of Peripheral Thyroid Hormone Levels by Activating and Inactivating Deiodinases

Annals of the New York Academy of Sciences, 1998

The main secretion product of the vertebrate thyroid gland is thyroxine or T 4. However, it is we... more The main secretion product of the vertebrate thyroid gland is thyroxine or T 4. However, it is well known that thyroid hormone receptors have a much higher affinity for 3, 5, 3′-triiodothyronine (T 3), which is considered to be the active thyroid hormone. This activation ...

Research paper thumbnail of Comparative study of iodothyronine outer ring and inner ring deiodinase activities in five teleostean fishes

Fish Physiology and …, 1998

The presence of outer ring deiodinating (ORD) and inner ring deiodinating (IRD) activities was in... more The presence of outer ring deiodinating (ORD) and inner ring deiodinating (IRD) activities was investigated in different tissues of Oreochromis niloticus (Nile tilapia), Clarias gariepinus (African catfish), Oncorhynchus mykiss (rainbow trout) and Scophthalmus maximus (turbot). High-K m rT 3 ORD is present in the kidney of most of the fishes studied, except in catfish. In turbot, besides the kidney, rT 3 ORD is also present in liver, heart and ovary. Low-K m T 4 ORD is found in the liver and low-K m T 3 IRD in the brain of all the fishes studied. In addition, low levels of low-K m T 3 IRD were demonstrated in gill and skin of Nile tilapia, liver of rainbow trout and gill and kidney of turbot. For the different teleosts, the biochemical properties of the different rT 3 -deiodinating enzymes mentioned, T 4 ORD in liver and T 3 IRD in brain and tilapia gill were compared to those of the deiodinases formerly characterized in Oreochromis aureus (blue tilapia).

Research paper thumbnail of Distribution and regulation of chicken growth hormone secretagogue receptor isoforms

General and Comparative Endocrinology, 2003

Chicken ghrelin has recently been isolated as a hormone which stimulates growth hormone and corti... more Chicken ghrelin has recently been isolated as a hormone which stimulates growth hormone and corticosterone secretion in chicken. Ghrelin mediates these actions in mammals by binding to the growth hormone secretagogue receptor (GHS-R). In this study, we describe the partial cloning of two chicken GHS-R (cGHS-R) isoforms: cGHS-R1a and cGHS-R1c. cGHS-R1a and cGHS-R1c cDNA show, respectively, 81 and 78% homology with the corresponding parts of the human GHS-R1a cDNA. In contrast to the human GHS-R1b isoform, which is truncated after transmembrane domain 5 (TM-5), the chicken GHS-R1c isoform lacks 16 amino acids in TM-6 suggesting that this isoform is not active in ghrelin signal transduction. The cystein residues, N-linked glycosylation sites and potential phosphorylation sites, found in the human GHS-R1a, were also conserved in both chicken isoforms. RT-PCR analysis demonstrated cGHS-R1a and cGHS-R1c mRNA expression in all tissues tested, except liver and pancreas, with highest levels in the pituitary and the hypothalamus. Intermediate levels of expression were detected, in descending order, in the ovary, telencephalon, heart, adrenal gland, cerebellum, and optic lobes whereas low expression was detected in the brainstem, lung, kidney, proventriculus, duodenum, and colon. Very low expression was found in skin, stomach, and muscle. cGHS-R1c was expressed in lower amounts than cGHS-R1a in all analysed tissues. Administration of 1 lM chicken ghrelin to pituitaries in vitro resulted in a down-regulation of both cGHS-R isoforms within 15 min, whereas after 1 h levels returned to control values. Growth hormone and corticosterone down-regulated cGHS-R1a and cGHS-R1c mRNA expression within 60 min of exposure, whereas growth hormone-releasing factor 1-29 (1 lM) only reduced cGHS-R1a mRNA expression after 60 min. Thyrotropin-releasing hormone (1 lM) did not alter cGHS-R expression.

Research paper thumbnail of Effects of experimental hypo- and hyperthyroidism on iodothyronine deiodinases in Nile tilapia, Oreochromis niloticus

Fish Physiology and Biochemistry, 1999

In the present study, we examined the effects of experimentally-induced increases or decreases in... more In the present study, we examined the effects of experimentally-induced increases or decreases in plasma concentrations of thyroid hormones on iodothyronine deiodinases in tilapia, Oreochromis niloticus. To obtain hyperthyroid tilapia, fish were injected with porcine follicle stimulating hormone (pFSH) 36 hours before sampling or fed on demand for 11 days with tilapia pellets containing 12 ppm T3. Tilapias were made

Research paper thumbnail of Transcriptional regulation of iodothyronine deiodinases during embryonic development

Molecular and Cellular Endocrinology, 2001

A single dose of chicken growth hormone (cGH) or dexamethasone acutely increases circulating T(3)... more A single dose of chicken growth hormone (cGH) or dexamethasone acutely increases circulating T(3) levels in 18-day-old chicken embryos through a reduction of hepatic type III iodothyronine deiodinase (D3). The data in the present study suggest that this decrease in D3 is induced by a direct downregulation of hepatic D3 gene transcription. The lack of effect of cGH or dexamethasone on brain and kidney D3 activity, furthermore suggests that both hormones affect peripheral thyroid hormone metabolism in a tissue specific manner. Dexamethasone administration also results in an increase in brain type II iodothyronine deiodinase (D2) activity and mRNA levels that is also regulated at a transcriptional level. In contrast, however, cGH has no effect on brain D2 activity, thereby suggesting that either GH cannot pass through the blood-brain barrier in chicken or that cGH and dexamethasone regulate thyroid hormone deiodination by different mechanisms. In addition, the very short half-life of D2 and D3 (t(1/2)<1 h) in comparison with the longer half life of type I iodothyronine deiodinase (D1, t(1/2)>8 h), allows for D2 and D3 to play a more prominent role in the acute regulation of peripheral thyroid hormone metabolism than D1.

Research paper thumbnail of Thyroid Hormone Sulfation in Chicken and Axolotl

Netherlands Journal of Zoology - NETH J ZOOL, 2000

ABSTRACT

Research paper thumbnail of Inhibition and activation of the thyroidal axis by the adrenal axis in vertebrates

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 1998

Hormones of the adrenal or interrenal axis and stress situations which induce elevated glucocorti... more Hormones of the adrenal or interrenal axis and stress situations which induce elevated glucocorticoid plasma levels (e.g. handling and starvation), inhibit thyroid function in growing and adult vertebrates. However, data indicate that during foetal and embryonic development (mammals and birds) or during larval growth and metamorphosis (fish and amphibians), the adrenal axis may stimulate thyroid function. Recent findings have provided some information concerning this stimulatory interference of the adrenal axis. In amphibians corticotropin releasing hormone and not thyrotropin releasing hormone is thyrotropic during metamorphosis, thus providing the substrate T4 necessary for T3 production. Other data indicate that the increase in plasma T3 at metamorphic climax may be the result of an inhibition of the T3 degrading activity, rather than stimulation of the T4 into T3 converting activity, and that glucocorticoids may be responsible for this. Also, in the chick embryo glucocorticoids effectively increase plasma T3 concentration by reducing the hepatic T3 degrading activity, whereas corticotropin releasing hormone also induces an elevation in the thyrotropin plasma levels and hence raises T4 concentrations which may function as a substrate for T3 production.

Research paper thumbnail of Identification of somatostatin receptors controlling growth hormone and thyrotropin secretion in the chicken using receptor subtype-specific agonists

Journal of Endocrinology, 2003

Somatostatin (SRIH) functions as an endocrine mediator in processes such as growth, immune resist... more Somatostatin (SRIH) functions as an endocrine mediator in processes such as growth, immune resistance and reproduction. Five SRIH receptors (sstr1-5) have been identified in mammals, where they are expressed in both the brain and peripheral tissues. To study the specific function of each receptor subtype, specific agonists (ag1-5) have been synthesized. The high degree of homology between mammalian and avian SRIH receptors suggests that these agonists might also be used in chickens. In this paper we describe two in vitro protocols (static incubation and perifusion system) to identify the SRIH receptors controlling the secretion of GH and TSH from the chicken pituitary. We found that basal GH or TSH secretion were never affected when SRIH or an agonist (1 µM) were added. SRIH diminished the GH as well as the TSH response to TSH-releasing hormone (TRH; 100 nM) in both systems. Our results have indicated that the SRIH actions at the level of the pituitary are regulated through specific receptor subtypes. In both the static and flow incubations, ag2 lowered the GH response to TRH, whereas stimulated TSH release was diminished by both ag2 and ag5. Ag3 and ag4 tended to increase rather than decrease the responsiveness of both pituitary cell types to TRH in perifusion studies. Our data have indicated that SRIH inhibits chicken pituitary function through sstr2 and sstr5. Only sstr2 seems to be involved in the control of chicken GH release, whereas both sstr2 and sstr5 inhibit induced GH secretion in mammals. The possible stimulatory action of ag3 and ag4 may point towards a species-specific function of sstr3 and sstr4. of chicken hypophyseal thyrotropes and development of a radioimmunological indicator for chicken TSH using monoclonal and polyclonal homologous antibodies in a subtractive strategy. General and Comparative Endocrinology 92 189-200.

Research paper thumbnail of Low submetamorphic doses of dexamethasone and thyroxine induce complete metamorphosis in the axolotl (Ambystoma mexicanum) when injected together

General and Comparative Endocrinology, 2004

Entanglement of functions between the adrenal (or interrenal) and thyroid axis has been well desc... more Entanglement of functions between the adrenal (or interrenal) and thyroid axis has been well described for all vertebrates and can be tracked down up to the level of gene expression. Both thyroid hormones and corticosteroids may induce morphological changes leading to metamorphosis climax in the neotenic Mexican axolotl (Ambystoma mexicanum). In a first series of experiments, metamorphosis was induced with an injection of 25 lg T 4 on three alternate days as judged by a decrease in body weight and tail height together with complete gill resorption. This injection also resulted in elevated plasma concentrations of T 3 and corticosterone. Previous results have indicated that the same dose of dexamethasone (DEX) is ineffective in this regard (Gen. Comp. Endocrinol. 127 (2002) 157). In a second series of experiments low doses of T 4 (0.5 lg) or DEX (5 lg) were ineffective to induce morphological changes. However, when these submetamorphic doses were injected together, morphological changes were observed within one week leading to complete metamorphosis. It is concluded that thyroid hormones combined with corticosteroids are essential for metamorphosis in the axolotl and that only high doses of either thyroid hormone or corticosteroid can induce morphological changes when injected separately.

Research paper thumbnail of Effect of the sex-linked dwarf gene on thyrotrophic and somatotrophic axes in the chick embryo

Plasma concentrations of thyroxine (T4), triiodothyronine (T3), reversed triiodothyronine (rT3), ... more Plasma concentrations of thyroxine (T4), triiodothyronine (T3), reversed triiodothyronine (rT3), and insulin-like growth factors I and II (IGF-I, IGF-II) together with peripheral 5'-monodeiodination activity were measured in both normal and sex-linked dwarf embryos between day 14 of incubation and day 1 posthatch. Plasma T4 levels increased gradually during embryonic development while T3 concentrations remained low until day 20, when a sharp increase was observed. rT3 levels also increased from day 14 and dropped on day 20 when T3 levels started to increase. 5'-monodeiodination activity was high on day 14 of incubation, decreased thereafter, and showed an increase at the time of air sac penetration together with increased T3 levels. At this stage, differences between normal and dwarf embryos were observed; the latter had lower nonsignificant 5'-Monodeiodination activity and lower (P less than 0.01) plasma T3 levels. Plasma IGF-II levels were high during the whole embryonic period studied. Dwarf embryos had lower (P less than 0.05) IGF-II levels at the time of hatching. IGF-I levels were high on days 14 and 16, declined afterwards, and started to increase again around hatching. With the exception of T3 and IGF-II levels, introduction of the dwarf gene did not cause major changes in the hormonal parameters studied. This may explain the identical body weight at hatching.

Research paper thumbnail of Hypothalamic hormones that release growth hormone stimulate hepatic 5'-monodeiodination activity in the chick embryo

Journal of Endocrinology, 1988

Plasma GH, tri-iodothyronine (T3), thyroxine (T4) and liver 5'-monodeiodination (5&#3... more Plasma GH, tri-iodothyronine (T3), thyroxine (T4) and liver 5'-monodeiodination (5'-D) activity were measured in 18-day-old chick embryos injected with thyrotrophin-releasing hormone (TRH) and human pancreatic growth hormone releasing factor (hpGRF). Injections of 0.1 and 1 microgram TRH and 1.5 micrograms hpGRF increased the concentration of plasma GH while injection of 15 micrograms hpGRF had no effect. Concentrations of plasma T3 were raised after injection of TRH or hpGRF. Injections of TRH but not of hpGRF raised the concentration of plasma T4. The increases in concentration of plasma T3 after injection of TRH or hpGRF were parallelled by increases in liver 5'-D activity. An injection of 0.25 micrograms T4 significantly raised the concentration of T4 in plasma but had no effect on plasma T3 or liver 5'-D activity. It is concluded that the release of chicken GH by TRH or hpGRF is responsible for the observed increase in plasma concentration of T3 and liver 5'-D activity.

Research paper thumbnail of Regulation of Thyroid Hormone Metabolism during Fasting and Refeeding in Chicken

General and Comparative Endocrinology, 1999

Fasting and refeeding have considerable effects on thyroid hormone metabolism. In the present stu... more Fasting and refeeding have considerable effects on thyroid hormone metabolism. In the present study, 8-day-old meat-type cockerels were subjected to a 2-day starvation period followed by 3 days' refeeding. Blood and tissue samples were collected at the start of the experiment, at 4, 24, and 48 h of starvation, and at 4, 8, 24, 48, and 72 h of refeeding. This study demonstrates that in chicken, fasting decreased plasma T(3) and TSH levels and increased plasma T(4) concentrations. This was accompanied by increased hepatic type III deiodinase (D3) and decreased renal D3 activity. There were no changes in hepatic or renal type I deiodinase (D1). Refeeding restored normal plasma T(3), T(4), and TSH levels, while hepatic D3 and renal D3 activities returned to prefasting levels. Again hepatic D1 was not affected, but renal D1 was lower than the ad libitum values during the entire refeeding period. These results confirm that liver D3 is involved in the regulation of plasma T(3) during fasting and refeeding in the chicken. Northern blot analysis demonstrated increased hepatic D3 mRNA levels during the first day of starvation that disappeared by the end of the second day; refeeding had no additional effects. These results suggest that in fasted chickens the rapid upregulation of hepatic D3 occurs predominantly at a pretranslational level, whereas the drop in hepatic D3 activity after refeeding is probably regulated at a posttranslational level. In addition, renal D3 may play a role in the regulation of local T(3) availability.

Research paper thumbnail of Differential expression of iodothyronine deiodinases in chicken tissues during the last week of embryonic development

General and Comparative Endocrinology, 2002

In the current study, the authors examined the type 1 (D1), type 2 (D2), and type 3 deiodinase (D... more In the current study, the authors examined the type 1 (D1), type 2 (D2), and type 3 deiodinase (D3) activity and mRNA expression patterns in thyroid, lung, brain, pituitary, heart, liver, spleen, gonads, skin, muscle, intestine, Fabricius' bursa, and kidney during the last week of chicken embryonic development and the first 2 days posthatch. The D3 was the most widely expressed, occurring in all examined tissues. Also, the D1 knows a widespread distribution, although no D1 activity or mRNA expression could be detected in the brain, the thyroid, the muscle, and the skin. In contrast, the D2 has a much more restricted expression pattern, since the brain is the only organ where, prior to hatching, both in vitro D2 activity and D2 mRNA expression can be detected. Taken together, these results demonstrate that during the last week of chicken embryonic development, the majority of tissues express D3, together with either D1 or D2, indicating that each tissue possesses the necessary tools to regulate local thyroid hormone levels at least partly independent from T(3) and T(4) levels in plasma. In addition, the deiodinase expression data could be correlated to certain thyroid hormone dependent tissue-specific developmental events. This strongly suggests that in birds, as in mammals and amphibians, the correct spatial and temporal expression of iodothyronine deiodinases are essential for normal embryonic development.