Frank Jong - Academia.edu (original) (raw)
Papers by Frank Jong
TBV – Tijdschrift voor Bedrijfs- en Verzekeringsgeneeskunde, 2011
... Ook vonden we geen correlaties tussen cortisol en de leeftijd bij aanvang van wer-ken in ploe... more ... Ook vonden we geen correlaties tussen cortisol en de leeftijd bij aanvang van wer-ken in ploegendienst (p=0,376) en het aantal werk-zame jaren in ploegendienst (p=0,476). De BMI was significant hoger in ploegendienst-werkers dan in dagdienstwerkers. ...
Andrology, 2013
Men with a history of congenital undescended testes (UDT) have an increased risk of fertility pro... more Men with a history of congenital undescended testes (UDT) have an increased risk of fertility problems. Despite no definitive proof, current guidelines recommend early surgical intervention because this may have a positive effect on future fertility potential by preventing degenerative changes of the testes in early life. Also surgical intervention facilitates observability of the testes in view of possible malignancy. We evaluated testicular function in adult men with previous UDT treated at different ages before puberty. A long-term follow-up study of men with previous UDT was performed. Andrological evaluation included medical history taking, physical examination, scrotal ultrasound, determination of reproductive hormones, and semen analysis. Findings were compared with those of a control group of men with normal testicular descent. The influence of age at orchiopexy on future fertility parameters was evaluated in a multivariate regression analysis. 62 men were included of whom s...
Psychoneuroendocrinology, 2008
The human FMR1 gene contains an unstable CGG-repeat in its 5' untranslated region. The repeat... more The human FMR1 gene contains an unstable CGG-repeat in its 5' untranslated region. The repeat length in the normal population is polymorphic (5-54 CGG-repeats). Individuals carrying lengths beyond 200 CGGs (i.e. the full mutation) show hypermethylation and as a consequence gene silencing of the FMR1 gene. The absence of the gene product FMRP causes the fragile X syndrome, the most common inherited form of mental retardation. Elderly carriers of the premutation (PM), which is defined as a repeat length between 55 and 200 CGGs, can develop a progressive neurodegenerative syndrome: fragile X-associated tremor/ataxia syndrome (FXTAS). The high FMR1 mRNA levels observed in cells from PM carriers have led to the hypothesis that FXTAS is caused by a pathogenic RNA gain-of-function mechanism. Apart from tremor/ataxia, specific psychiatric symptoms have been described in PM carriers with or without FXTAS. Since these symptoms could arise from elevated stress hormone levels, we investigat...
Cancer research, Jan 15, 2001
Glucocorticoids play an important role in the treatment of a number of hematological malignancies... more Glucocorticoids play an important role in the treatment of a number of hematological malignancies, such as multiple myeloma. The effects of glucocorticoids are mediated through the glucocorticoid receptor alpha, the abundance of which can be modulated by alternative splicing of the glucocorticoid receptor mRNA. Two splice variants of the glucocorticoid receptor mRNA have been described: glucocorticoid receptor beta, which reportedly has a dominant negative effect on the actions of the glucocorticoid receptor alpha, and glucocorticoid receptor P, of which the effects are unknown. In this study, we have investigated the expression levels of these two splice variants at the mRNA level in multiple myeloma cells and in a number of other hematological tumors. Although the glucocorticoid receptor beta mRNA was, if at all, expressed at very low levels, considerable amounts (up to 50% of the total glucocorticoid receptor mRNA) glucocorticoid receptor P mRNA was present in most hematological ...
British journal of cancer, 2000
The possible role of activin in the regulation of malignant prostatic growth was studied using RN... more The possible role of activin in the regulation of malignant prostatic growth was studied using RNAase protection assays of activin receptors, inhibin/activin subunits and follistatin mRNAs in the human prostatic carcinoma cell lines LNCaP-FGC, -R and -LNO, in human prostatic carcinoma xenografts and in human prostatic tissue. Activin receptor types IA (ActRIA), IB (ActRIB), IIA (ActRIIA) and IIB (ActRIIB) mRNAs were generally expressed in prostate epithelial cells, with significantly lower levels of ActRIB mRNA in prostate tumour material when compared to non-malignant tissue (P < 0.05; Mann-Whitney U-test). Inhibin/activin betaA- and betaB-subunit mRNA expression was also found in prostate tissue. Androgen-independent xenografts expressed significantly lower amounts of betaB-subunit mRNA when compared to androgen-dependent xenografts (P< 0.05). While betaB-subunit mRNA was expressed by LNCaP-FGC and -LNO cells, virtually no expression was found in the androgen-independent LNC...
Anti-Müller-hormoon (AMH) is een lid van de fami- lie van groei- en differentiatiefactoren, waarv... more Anti-Müller-hormoon (AMH) is een lid van de fami- lie van groei- en differentiatiefactoren, waarvan ook TGFβ β, activine en de BMP's deel uitmaken. AMH heeft effecten via een combinatie van de AMH-recep- tor type II, een aantal activinereceptorachtige kina- ses (ALK's) en intracellulaire Smad-eiwitten. AMH wordt geproduceerd in Sertoli-cellen in de tes- tis. Tijdens de vroegfoetale periode onderdrukt het de
Marcus CL. Effect of sleep stage on breathing in children with central hypoventilation. The early... more Marcus CL. Effect of sleep stage on breathing in children with central hypoventilation. The early literature suggests that hypoventilation in infants with congenital central hypoventilation syndrome (CHS) is less severe during rapid eye movement (REM) than during non-REM (NREM) sleep. However, this supposition has not been rigorously tested, and subjects older than infancy have not been studied. Given the differences in anatomy, physiology, and REM sleep distribution between infants and older children, and the reduced number of limb movements during REM sleep, we hypothesized that older subjects with CHS would have more severe hypoventilation during REM than NREM sleep. Nine subjects with CHS, aged (mean Ϯ SD) 13 Ϯ 7 yr, were studied. Spontaneous ventilation was evaluated by briefly disconnecting the ventilator under controlled circumstances. Arousal was common, occurring in 46% of REM vs. 38% of NREM trials [not significant (NS)]. Central apnea occurred during 31% of REM and 54% of NREM trials (NS). Although minute ventilation declined precipitously during both REM and NREM trials, hypoventilation was less severe during REM (drop in minute ventilation of 65 Ϯ 23%) than NREM (drop of 87 Ϯ 16%, P ϭ 0.036). Despite large changes in gas exchange during trials, there was no significant change in heart rate during either REM or NREM sleep. We conclude that older patients with CHS frequently have arousal and central apnea, in addition to hypoventilation, when breathing spontaneously during sleep. The hypoventilation in CHS is more severe during NREM than REM sleep. We speculate that this may be due to increased excitatory inputs to the respiratory system during REM sleep.
International Journal of Pancreatology, 1992
The results of a previous 4-mo study in azaserine-treated rats and BOP-treated hamsters indicated... more The results of a previous 4-mo study in azaserine-treated rats and BOP-treated hamsters indicated that orchiectomy inhibited pancreatic growth and development of putative preneoplastic lesions in the exocrine pancreas of rats but not hamsters. This 12-mo study was carried out to investigate the effects of orchiectomy, alone and in combination with testosterone, and of treatment with cyproterone acetate on pancreatic carcinogenesis in azaserine-treated rats and BOP-treated hamsters. Treatment started 4 mo after injection of the carcinogen. In orchiectomized rats, pancreatic wt was lower than in controls, whereas pancreatic wt of orchiectomized rats treated with testosterone was similar to that of controls. Both orchiectomy and cyproterone acetate caused a decrease in body wt gain and had an inhibitory effect on pancreatic carcinogenesis. Testosterone treatment did not influence the inhibitory effects of orchiectomy on body wt gain and on pancreatic carcinogenesis. In hamsters, neither orchiectomy, alone or in combination with testosterone, nor cyproterone acetate (CA) affected pancreatic growth or pancreatic carcinogenesis. This study indicates that testosterone plays a minor role in the development of pancreatic tumors induced in rats by azaserine but not in that of pancreatic tumors induced in hamsters by BOP.
Steroids, 1996
Recent studies demonstrate that primary (hereditary) abnormalities in the glucocorticoid receptor... more Recent studies demonstrate that primary (hereditary) abnormalities in the glucocorticoid receptor gene make 6.6% of the normal population relatively "hypersensitive" to glucocorticoids, while 2.3% are relatively "resistant." These abnormalities might explain why some individuals develop severe adverse effects during low dose glucocorticoid therapy, while others do not develop side effects even during long-term therapy with a much higher dose. Awareness of this heterogeneity in glucocorticoid sensitivity in the normal population might eventually allow the prediction of a "safe" dose of glucocorticoid in individual patients.
Reproduction, 1983
Beste Solomon, Wat een verrassing! Ik rond op het ogenblik een aantal samenwerkingsprojecten af e... more Beste Solomon, Wat een verrassing! Ik rond op het ogenblik een aantal samenwerkingsprojecten af en verwacht dat mijn laatse publicaties later dit jaar of begin volgend jaar zullen verschijnen. Met hartelijke groet, ook aan Els, Frank View project Shalom bar-ami Summary. Oocyte maturation inhibitor (OMI), inhibin, progesterone and oestradiol\x=req-\ 17\g=b\ concentrations were measured in fluid collected from small ( < 3 mm), medium size (3\p=n-\6mm) and large ( > 6 mm) porcine ovarian follicles, which were obtained on Days 5, 10, 15 and 18 of the oestrous cycle and at 24 h after the onset of oestrus. Concentrations of OMI decreased with increasing follicle diameter (P < 0\m=.\05),independent of the stage of the oestrous cycle. Concentrations of inhibin showed a tendency to decrease with increasing follicle diameter on Days 10, 15 and 18, but not on Day 5 of the cycle. Concentrations of OMI and inhibin in the largest follicles were low before the onset of oestrus, and were essentially unaltered 24 h later. A positive correlation was found between OMI and inhibin concentrations, whereas the correlation between inhibin concentration and log (progesterone concentrations) was negative.
Neurobiology of Aging, 2008
Objective: Elevated glucocorticoid levels are associated with dementia. A glucocorticoid receptor... more Objective: Elevated glucocorticoid levels are associated with dementia. A glucocorticoid receptor gene variant (ER22/23EK) is related to relative glucocorticoid resistance. We investigated whether the ER22/23EK allele is associated with dementia and structural brain abnormalities. Methods: This study was performed in two prospective population-based cohort studies among elderly. The first study included 6034 participants who were screened for dementia (mean follow-up 5.8 years). The second study included 1011 elderly subjects with an MRI at baseline and follow-up. The ER22/23EK allele was assessed for association with dementia, cognitive function and white matter lesions. Results: The ER22/23EK allele was associated with a decreased risk of dementia. Among non-demented participants, ER22/23EK-carriers had a better performance on psychomotor speed tests than non-carriers. No differences were found in memory function between genotypes. In addition, both presence and progression of white matter lesions was lower in ER22/23EK-carriers. No association was found with brain atrophy on MRI. Conclusions: Our findings suggest a protective effect of the ER22/23EK allele on the risk of dementia and white matter lesions.
Molecular Endocrinology, 2005
CITATIONS 77 READS 39 9 authors, including: Some of the authors of this publication are also work... more CITATIONS 77 READS 39 9 authors, including: Some of the authors of this publication are also working on these related projects: Vitamin D and inflammation in pregnancy View project Beste Solomon, Wat een verrassing! Ik rond op het ogenblik een aantal samenwerkingsprojecten af en verwacht dat mijn laatse publicaties later dit jaar of begin volgend jaar zullen verschijnen. Met hartelijke groet, ook aan Els, Frank View project 11-Hydroxysteroid dehydrogenase type 1 (11-HSD1) plays an important role in the prereceptor regulation of corticosteroids by locally converting cortisone into active cortisol. To investigate the impact of this mechanism on osteoblast development, we have characterized 11-HSD1 activity and regulation in a differentiating human osteoblast cell line (SV-HFO). Continuous treatment with the synthetic glucocorticoid dexamethasone induces differentiation of SV-HFO cells during 21 d of culture. Using this cell system, we showed an inverse relationship between 11-HSD1 activity and osteoblast differentiation. 11-HSD1 mRNA expression and activity were low and constant in differentiating osteoblasts. However, in the absence of differentiation (no dexamethasone), 11-HSD1 mRNA and activity increased strongly from d 12 of culture onward, with a peak around d 19.
Journal of the Renin-Angiotensin-Aldosterone System, 2012
CITATIONS 6 READS 17 5 authors, including:
Journal of Molecular Endocrinology, 2007
The glucocorticoid receptor (GR) is widely expressed in various tissues throughout the human body... more The glucocorticoid receptor (GR) is widely expressed in various tissues throughout the human body. At least three different 3 0 -splice variants of the GR have been reported: GR-a, which is functionally active; GR-b, which is a dominant negative inhibitor of GR-a function; and GR-P, which is thought to activate the function of GR-a. At least seven different variants for exon 1 exist, 1A-1F and 1H, each with its own promoter. In this study, we explored if tissue-specific splicing of the 3 0 -end variants of the GR is influenced by alternative promoter usage. cDNAs of different tissues and cell lines were used to investigate which part of transcripts carrying each of the three major variants for exons 1, 1A, 1B, or 1C, encodes for the splice variants GR-a, GR-b, and GR-P. Our data demonstrate that the expression of GR-a is preferentially regulated by promoter 1C and that for the expression of GR-P promoter 1B is predominantly used. This indicates that regulation of GR splice variants could partly occur through selective use of the multiple promoters, and that this is another way to sensitize cells and tissues to the different activities of the GR isoforms.
Journal of Endocrinology, 1996
This study describes the effects of litter size and acute suckling on the synthesis and release o... more This study describes the effects of litter size and acute suckling on the synthesis and release of hypothalamic TRH, as indirectly estimated by determination of hypothalamic prothyrotrophin-releasing hormone (proTRH) mRNA and median eminence TRH content. The effects of litter size (five or ten pups) were studied throughout lactation, while suckling-induced acute changes were analyzed on day 13 of lactation in dams with ten pups. In view of the enhanced adrenal activity during lactation and recent evidence that corticosteroids have negative effects on hypothalamic TRH, we also studied adrenalectomized (ADX) dams treated with corticosterone to maintain basal plasma corticosterone levels. In addition to an increased plasma level of prolactin (PRL), adrenal weight and plasma corticosterone increased, while plasma TSH, tri-iodothyronine (T3), thyroxine (T4) and free T4 (FT4) levels decreased during lactation. Litter size correlated positively with plasma PRL, adrenal weight and plasma corticosterone. No effect of litter size was observed on plasma T3, but rats with ten pups had lower plasma TSH, T4 and FT4 than rats with a five-pup litter. Compared with dioestrous rats, lactating rats showed an increased hypothalamic proTRH mRNA content on day 2, but not on days 8 and 15 of lactation. Median eminence TRH in lactating rats gradually increased until day 15 and decreased thereafter. Acute suckling, after a 6-h separation of mother and pups, rapidly increased plasma PRL and corticosterone in the mothers, but had no effects on plasma TSH and thyroid hormone levels. Hypothalamic proTRH mRNA increased twofold after 0.5 h of suckling, and then gradually returned to presuckling values after 6 h. Compared with sham-operated rats, corticosterone-substituted ADX rats with ten pups had increased plasma PRL and TSH, hypothalamic proTRH mRNA and pituitary TSH beta mRNA on day 15 of lactation. Moreover, while acute suckling did not enhance TSH release in sham-operated rats, it provoked not only PRL but also TSH release in corticosterone-substituted ADX dams. It is concluded that suckling exerts a rapid, positive effect on hypothalamic proTRH mRNA content. However, the concurrent enhanced adrenal activity has negative effects on hypothalamic proTRH gene expression resulting in a suppressed hypophysial-thyroid axis during lactation. While TRH appears to play a role in PRL release during the first days of lactation and during acute suckling, TRH seems not important in maintaining PRL secretion during continued suckling.
Journal of Endocrinology, 1996
The reduced thyroid activity during short-term starvation is associated with a lowered hypothalam... more The reduced thyroid activity during short-term starvation is associated with a lowered hypothalamic synthesis and secretion of TRH. However, little is known about the cause of the reduced thyroid function during prolonged malnutrition. We have therefore studied the effects of food reduction to one-third of normal (FR33) on the hypothalamus-pituitary-thyroid axis of male and female Wistar rats. After 3 weeks body weights of FR33 rats were almost 50% lower than those of controls. In both sexes, FR33 caused marked increases in serum corticosterone, and decreases in serum TSH, thyroxine (T4), free T4, tri-iodothyronine (T3) and free T3. While the free T3 fraction (FFT3) in serum decreased, the free T4 fraction (FFT4) tended to increase. Electrophoretic analysis indicated that decreased FFT3 was correlated with an increased thyroxine-binding globulin, while the increase in FFT4 seemed due to a decreased thyroxine-binding prealbumin binding capacity. Total RNA and proTRH mRNA in the hypothalamus were not affected by FR33. Median eminence and posterior pituitary TRH content tended to increase in FR33 rats, suggesting that hypothalamic TRH release is reduced in FR33 rats. Anterior pituitary TSH content was decreased by FR33 in both sexes, but pituitary TSH beta mRNA and TRH receptor status were not affected except for increased pituitary TSH beta mRNA in female FR33 rats. Although FR33 had no effect on pituitary weight, pituitary RNA and membrane protein content in FR33 rats were 50-70% lower than values in controls. In conclusion, prolonged food reduction suppresses the pituitary-thyroid axis in rats. In contrast to short-term food deprivation, the mechanism whereby serum TSH is suppressed does not appear to involve decreases in proTRH gene expression, but may include effects on pituitary mRNA translation. Our results further support the hypothesis that TSH release may be lowered by increased corticosterone secretion, although the mechanism of this effect may differ between acute starvation and prolonged food reduction.
Journal of Endocrinology, 1993
Direct effects of testosterone on gonadotrophins at the pituitary level were studied in intact an... more Direct effects of testosterone on gonadotrophins at the pituitary level were studied in intact and castrated immature (age 10 days) and mature (70 days) male rats. Gonadotrophin-releasing hormone action was blocked by treatment with a potent GnRH antagonist, Ac-D-pClPhe-D-pClPhe-D-Trp-Ser-Tyr-D-Arg-Leu-Arg-Pro-D-Ala-+ ++NH2CH3COOH (Ant; Organon 30276; 1.0 mg/kg body weight per day) injected subcutaneously. Silicone elastomer capsules were used for the testosterone treatment. Both treatments commenced on the day of orchiectomy and lasted for 7 days. In adult male rats Ant treatment suppressed serum testosterone from 9.5 +/- 2.5 (S.E.M.) nmol/l to below the limit of detection (< 0.10 nmol/l; P < 0.01), and the testosterone implants reversed the decrease. Treatment with Ant decreased the pituitary content of FSH-beta subunit mRNA in intact and orchiectomized rats to 14% of their respective controls (P < 0.01). These levels were increased to 80-81% of controls (not significant) in both groups by combined treatment with testosterone and Ant. Orchiectomy alone increased FSH-beta subunit mRNA by 202% (P < 0.01). In intact immature rats Ant treatment decreased the level of pituitary FSH-beta subunit mRNA to 21% (P < 0.01), and a partial recovery (P < 0.01) to 42% of controls was observed with combined Ant+testosterone treatment. In contrast, in orchiectomized immature rats, where ANT decreased FSH-beta subunit levels to 48% of controls (P < 0.01), testosterone was able to reverse these mRNA levels completely (114% of controls). No evidence for the direct pituitary effects of testosterone were found in the mRNA of the common alpha or LH-beta subunits. In adult rats, the testicular inhibin alpha and beta A subunit mRNA levels were increased (P < 0.01) by Ant+testosterone compared with Ant-treated animals, but there were no differences in serum immunoreactive inhibin between any of the uncastrated adult groups. In intact immature rats, Ant+testosterone treatment increased (P < 0.01) inhibin beta A subunit mRNA levels compared with controls and Ant-treated animals. Ant decreased the level fo peripheral inhibin immunoreactivity from 8.3 +/- 2.0 U/ml to 2.1 +/- 0.4 U/ml (P < 0.01) and testosterone reversed it to 5.8 +/- 0.6 U/ml (not significant). In conclusion, our observations indicated that testosterone is able to stimulate FSH gene expression and secretion directly in immature and adult rats, but the testosterone response is enhanced at both ages by orchiectomy, even more so in the immature rat.(ABSTRACT TRUNCATED AT 400 WORDS)
Journal of Endocrinology, 2012
ABSTRACT The antifungal agent ketoconazole is often used to suppress cortisol production in patie... more ABSTRACT The antifungal agent ketoconazole is often used to suppress cortisol production in patients with Cushing's syndrome. However, ketoconazole has serious side-effects and is hepatotoxic. Here, the in vitro effects of ketoconazole and fluconazole, which might be less toxic, on human adrenocortical steroidogenesis were compared.The effects on steroidogenesis were examined in primary cultures of nine human adrenocortical tissues and two human adrenocortical carcinoma cell lines. Moreover, the effects on mRNA expression levels of steroidogenic enzymes and cell growth were assessed.Ketoconazole significantly inhibited 11-deoxycortisol- (H295R cells; maximum inhibition 99%;EC50 0.73μM) and cortisol production (HAC15 cells;81%;EC50 0.26μM and primary cultures (mean EC50 0.75μM)). In cultures of normal adrenal cells, ketoconazole increased pregnenolone, progesterone and deoxycorticosterone levels, while concentrations of 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, DHEA and androstenedione decreased. Fluconazole also inhibited 11-deoxycortisol production in H295R cells (47%;only at 1mM) and cortisol production in HAC15 cells (maximum inhibition 55%;EC50 35μM) and primary cultures (mean EC50 67.7μM). In the cultures of normal adrenals, fluconazole suppressed corticosterone, 17-hydroxypregnenolone and androstenedione levels, whereas concentrations of progesterone, deoxycorticosterone and 11-deoxycortisol increased. Fluconazole(1mM) slightly increased STAR mRNA expression in both cell-lines.Neither compound affected mRNA levels of other steroidogenic enzymes or cell number.In conclusion, by inhibiting 11β-hydroxylase and 17-hydroxylase activity, pharmacological concentrations of fluconazole dose-dependently inhibit cortisol production in human adrenocortical cells in vitro. Although fluconazole seems less potent than ketoconazole, it might become an alternative for ketoconazole to control hypercortisolism in Cushing's syndrome. Furthermore, patients receiving fluconazole because of mycosis might be at risk for developing adrenocortical insufficiency.
Journal of Endocrinology, 1986
Inhibin was partially purified from bovine follicular fluid using chromatography on immobilized P... more Inhibin was partially purified from bovine follicular fluid using chromatography on immobilized Procion Red 3B and anion-exchange chromatography. Ovariectomized Texel ewes were immunized against the inhibin-containing fraction from the Procion Red 3B column and the immune response was subsequently boosted with similar fractions or with the preparation obtained from the anion-exchange column. The potencies of the resulting antisera were evaluated in an in-vitro bioassay system for estimating inhibin activity, using dispersed rat pituitary cells. The antisera were found to inhibit the bioactivity of inhibin preparations from ovarian follicular fluid of bovine, porcine, ovine or human origin, as well as inhibin activity in ovine testicular lymph and rete testis fluid, in culture media from rat granulosa and rat Sertoli cells and in homogenates of rat ovaries and testes. These results indicate that the inhibin molecules from several species contain a common bioactive moiety. The results also showed that the antiserum was more effective in neutralizing inhibin activity from ovarian than from testicular sources in both sheep and rat, indicating a sex-related difference in the inhibin molecules within a species.
Journal of Endocrinology, 1995
Recent evidence shows that thyrotrophin-releasing hormone (TRH) immunoreactivity in the rat anter... more Recent evidence shows that thyrotrophin-releasing hormone (TRH) immunoreactivity in the rat anterior pituitary gland is accounted for by the TRH-like tripeptide pyroglutamyl-glutamyl-prolineamide (pGlu-Glu-ProNH2, < EEP-NH2). The present study was undertaken to investigate further the regulation, localization and possible intrapituitary function of < EEP-NH2. Anterior pituitary levels of < EEP-NH2 were determined between days 5 and 35 of life, during the oestrous cycle and after treatment with the luteinizing hormone-releasing hormone (LHRH) antagonist Org 30276. Treatment of adult males with the LHRH antagonist either for 1 day (500 micrograms/100 g body weight) or for 5 days (50 micrograms/100 g body weight) reduced anterior pituitary < EEP-NH2 levels by 25-30% (P < 0.05 versus saline-treated controls). Anterior pituitary < EEP-NH2 increased between days 5 and 35 of life. In females, these levels were 2- to 3-fold higher (P < 0.05) than in males between days 15 and 25 after birth; these changes corresponded with the higher plasma follicle-stimulating hormone (FSH) levels in the female rats. After day 25, < EEP-NH2 levels in female rats decreased in parallel with a decrease in plasma FSH. Injections with the LHRH antagonist (500 micrograms/100 g body weight), starting on day 22 of life, led to reduced contents of < EEP-NH2 in the anterior pituitary gland of female rats on days 26 and 30 (55 and 35% decrease respectively). Levels of < EEP-NH2 in the anterior pituitary gland did not change significantly during the oestrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
TBV – Tijdschrift voor Bedrijfs- en Verzekeringsgeneeskunde, 2011
... Ook vonden we geen correlaties tussen cortisol en de leeftijd bij aanvang van wer-ken in ploe... more ... Ook vonden we geen correlaties tussen cortisol en de leeftijd bij aanvang van wer-ken in ploegendienst (p=0,376) en het aantal werk-zame jaren in ploegendienst (p=0,476). De BMI was significant hoger in ploegendienst-werkers dan in dagdienstwerkers. ...
Andrology, 2013
Men with a history of congenital undescended testes (UDT) have an increased risk of fertility pro... more Men with a history of congenital undescended testes (UDT) have an increased risk of fertility problems. Despite no definitive proof, current guidelines recommend early surgical intervention because this may have a positive effect on future fertility potential by preventing degenerative changes of the testes in early life. Also surgical intervention facilitates observability of the testes in view of possible malignancy. We evaluated testicular function in adult men with previous UDT treated at different ages before puberty. A long-term follow-up study of men with previous UDT was performed. Andrological evaluation included medical history taking, physical examination, scrotal ultrasound, determination of reproductive hormones, and semen analysis. Findings were compared with those of a control group of men with normal testicular descent. The influence of age at orchiopexy on future fertility parameters was evaluated in a multivariate regression analysis. 62 men were included of whom s...
Psychoneuroendocrinology, 2008
The human FMR1 gene contains an unstable CGG-repeat in its 5' untranslated region. The repeat... more The human FMR1 gene contains an unstable CGG-repeat in its 5' untranslated region. The repeat length in the normal population is polymorphic (5-54 CGG-repeats). Individuals carrying lengths beyond 200 CGGs (i.e. the full mutation) show hypermethylation and as a consequence gene silencing of the FMR1 gene. The absence of the gene product FMRP causes the fragile X syndrome, the most common inherited form of mental retardation. Elderly carriers of the premutation (PM), which is defined as a repeat length between 55 and 200 CGGs, can develop a progressive neurodegenerative syndrome: fragile X-associated tremor/ataxia syndrome (FXTAS). The high FMR1 mRNA levels observed in cells from PM carriers have led to the hypothesis that FXTAS is caused by a pathogenic RNA gain-of-function mechanism. Apart from tremor/ataxia, specific psychiatric symptoms have been described in PM carriers with or without FXTAS. Since these symptoms could arise from elevated stress hormone levels, we investigat...
Cancer research, Jan 15, 2001
Glucocorticoids play an important role in the treatment of a number of hematological malignancies... more Glucocorticoids play an important role in the treatment of a number of hematological malignancies, such as multiple myeloma. The effects of glucocorticoids are mediated through the glucocorticoid receptor alpha, the abundance of which can be modulated by alternative splicing of the glucocorticoid receptor mRNA. Two splice variants of the glucocorticoid receptor mRNA have been described: glucocorticoid receptor beta, which reportedly has a dominant negative effect on the actions of the glucocorticoid receptor alpha, and glucocorticoid receptor P, of which the effects are unknown. In this study, we have investigated the expression levels of these two splice variants at the mRNA level in multiple myeloma cells and in a number of other hematological tumors. Although the glucocorticoid receptor beta mRNA was, if at all, expressed at very low levels, considerable amounts (up to 50% of the total glucocorticoid receptor mRNA) glucocorticoid receptor P mRNA was present in most hematological ...
British journal of cancer, 2000
The possible role of activin in the regulation of malignant prostatic growth was studied using RN... more The possible role of activin in the regulation of malignant prostatic growth was studied using RNAase protection assays of activin receptors, inhibin/activin subunits and follistatin mRNAs in the human prostatic carcinoma cell lines LNCaP-FGC, -R and -LNO, in human prostatic carcinoma xenografts and in human prostatic tissue. Activin receptor types IA (ActRIA), IB (ActRIB), IIA (ActRIIA) and IIB (ActRIIB) mRNAs were generally expressed in prostate epithelial cells, with significantly lower levels of ActRIB mRNA in prostate tumour material when compared to non-malignant tissue (P < 0.05; Mann-Whitney U-test). Inhibin/activin betaA- and betaB-subunit mRNA expression was also found in prostate tissue. Androgen-independent xenografts expressed significantly lower amounts of betaB-subunit mRNA when compared to androgen-dependent xenografts (P< 0.05). While betaB-subunit mRNA was expressed by LNCaP-FGC and -LNO cells, virtually no expression was found in the androgen-independent LNC...
Anti-Müller-hormoon (AMH) is een lid van de fami- lie van groei- en differentiatiefactoren, waarv... more Anti-Müller-hormoon (AMH) is een lid van de fami- lie van groei- en differentiatiefactoren, waarvan ook TGFβ β, activine en de BMP's deel uitmaken. AMH heeft effecten via een combinatie van de AMH-recep- tor type II, een aantal activinereceptorachtige kina- ses (ALK's) en intracellulaire Smad-eiwitten. AMH wordt geproduceerd in Sertoli-cellen in de tes- tis. Tijdens de vroegfoetale periode onderdrukt het de
Marcus CL. Effect of sleep stage on breathing in children with central hypoventilation. The early... more Marcus CL. Effect of sleep stage on breathing in children with central hypoventilation. The early literature suggests that hypoventilation in infants with congenital central hypoventilation syndrome (CHS) is less severe during rapid eye movement (REM) than during non-REM (NREM) sleep. However, this supposition has not been rigorously tested, and subjects older than infancy have not been studied. Given the differences in anatomy, physiology, and REM sleep distribution between infants and older children, and the reduced number of limb movements during REM sleep, we hypothesized that older subjects with CHS would have more severe hypoventilation during REM than NREM sleep. Nine subjects with CHS, aged (mean Ϯ SD) 13 Ϯ 7 yr, were studied. Spontaneous ventilation was evaluated by briefly disconnecting the ventilator under controlled circumstances. Arousal was common, occurring in 46% of REM vs. 38% of NREM trials [not significant (NS)]. Central apnea occurred during 31% of REM and 54% of NREM trials (NS). Although minute ventilation declined precipitously during both REM and NREM trials, hypoventilation was less severe during REM (drop in minute ventilation of 65 Ϯ 23%) than NREM (drop of 87 Ϯ 16%, P ϭ 0.036). Despite large changes in gas exchange during trials, there was no significant change in heart rate during either REM or NREM sleep. We conclude that older patients with CHS frequently have arousal and central apnea, in addition to hypoventilation, when breathing spontaneously during sleep. The hypoventilation in CHS is more severe during NREM than REM sleep. We speculate that this may be due to increased excitatory inputs to the respiratory system during REM sleep.
International Journal of Pancreatology, 1992
The results of a previous 4-mo study in azaserine-treated rats and BOP-treated hamsters indicated... more The results of a previous 4-mo study in azaserine-treated rats and BOP-treated hamsters indicated that orchiectomy inhibited pancreatic growth and development of putative preneoplastic lesions in the exocrine pancreas of rats but not hamsters. This 12-mo study was carried out to investigate the effects of orchiectomy, alone and in combination with testosterone, and of treatment with cyproterone acetate on pancreatic carcinogenesis in azaserine-treated rats and BOP-treated hamsters. Treatment started 4 mo after injection of the carcinogen. In orchiectomized rats, pancreatic wt was lower than in controls, whereas pancreatic wt of orchiectomized rats treated with testosterone was similar to that of controls. Both orchiectomy and cyproterone acetate caused a decrease in body wt gain and had an inhibitory effect on pancreatic carcinogenesis. Testosterone treatment did not influence the inhibitory effects of orchiectomy on body wt gain and on pancreatic carcinogenesis. In hamsters, neither orchiectomy, alone or in combination with testosterone, nor cyproterone acetate (CA) affected pancreatic growth or pancreatic carcinogenesis. This study indicates that testosterone plays a minor role in the development of pancreatic tumors induced in rats by azaserine but not in that of pancreatic tumors induced in hamsters by BOP.
Steroids, 1996
Recent studies demonstrate that primary (hereditary) abnormalities in the glucocorticoid receptor... more Recent studies demonstrate that primary (hereditary) abnormalities in the glucocorticoid receptor gene make 6.6% of the normal population relatively "hypersensitive" to glucocorticoids, while 2.3% are relatively "resistant." These abnormalities might explain why some individuals develop severe adverse effects during low dose glucocorticoid therapy, while others do not develop side effects even during long-term therapy with a much higher dose. Awareness of this heterogeneity in glucocorticoid sensitivity in the normal population might eventually allow the prediction of a "safe" dose of glucocorticoid in individual patients.
Reproduction, 1983
Beste Solomon, Wat een verrassing! Ik rond op het ogenblik een aantal samenwerkingsprojecten af e... more Beste Solomon, Wat een verrassing! Ik rond op het ogenblik een aantal samenwerkingsprojecten af en verwacht dat mijn laatse publicaties later dit jaar of begin volgend jaar zullen verschijnen. Met hartelijke groet, ook aan Els, Frank View project Shalom bar-ami Summary. Oocyte maturation inhibitor (OMI), inhibin, progesterone and oestradiol\x=req-\ 17\g=b\ concentrations were measured in fluid collected from small ( < 3 mm), medium size (3\p=n-\6mm) and large ( > 6 mm) porcine ovarian follicles, which were obtained on Days 5, 10, 15 and 18 of the oestrous cycle and at 24 h after the onset of oestrus. Concentrations of OMI decreased with increasing follicle diameter (P < 0\m=.\05),independent of the stage of the oestrous cycle. Concentrations of inhibin showed a tendency to decrease with increasing follicle diameter on Days 10, 15 and 18, but not on Day 5 of the cycle. Concentrations of OMI and inhibin in the largest follicles were low before the onset of oestrus, and were essentially unaltered 24 h later. A positive correlation was found between OMI and inhibin concentrations, whereas the correlation between inhibin concentration and log (progesterone concentrations) was negative.
Neurobiology of Aging, 2008
Objective: Elevated glucocorticoid levels are associated with dementia. A glucocorticoid receptor... more Objective: Elevated glucocorticoid levels are associated with dementia. A glucocorticoid receptor gene variant (ER22/23EK) is related to relative glucocorticoid resistance. We investigated whether the ER22/23EK allele is associated with dementia and structural brain abnormalities. Methods: This study was performed in two prospective population-based cohort studies among elderly. The first study included 6034 participants who were screened for dementia (mean follow-up 5.8 years). The second study included 1011 elderly subjects with an MRI at baseline and follow-up. The ER22/23EK allele was assessed for association with dementia, cognitive function and white matter lesions. Results: The ER22/23EK allele was associated with a decreased risk of dementia. Among non-demented participants, ER22/23EK-carriers had a better performance on psychomotor speed tests than non-carriers. No differences were found in memory function between genotypes. In addition, both presence and progression of white matter lesions was lower in ER22/23EK-carriers. No association was found with brain atrophy on MRI. Conclusions: Our findings suggest a protective effect of the ER22/23EK allele on the risk of dementia and white matter lesions.
Molecular Endocrinology, 2005
CITATIONS 77 READS 39 9 authors, including: Some of the authors of this publication are also work... more CITATIONS 77 READS 39 9 authors, including: Some of the authors of this publication are also working on these related projects: Vitamin D and inflammation in pregnancy View project Beste Solomon, Wat een verrassing! Ik rond op het ogenblik een aantal samenwerkingsprojecten af en verwacht dat mijn laatse publicaties later dit jaar of begin volgend jaar zullen verschijnen. Met hartelijke groet, ook aan Els, Frank View project 11-Hydroxysteroid dehydrogenase type 1 (11-HSD1) plays an important role in the prereceptor regulation of corticosteroids by locally converting cortisone into active cortisol. To investigate the impact of this mechanism on osteoblast development, we have characterized 11-HSD1 activity and regulation in a differentiating human osteoblast cell line (SV-HFO). Continuous treatment with the synthetic glucocorticoid dexamethasone induces differentiation of SV-HFO cells during 21 d of culture. Using this cell system, we showed an inverse relationship between 11-HSD1 activity and osteoblast differentiation. 11-HSD1 mRNA expression and activity were low and constant in differentiating osteoblasts. However, in the absence of differentiation (no dexamethasone), 11-HSD1 mRNA and activity increased strongly from d 12 of culture onward, with a peak around d 19.
Journal of the Renin-Angiotensin-Aldosterone System, 2012
CITATIONS 6 READS 17 5 authors, including:
Journal of Molecular Endocrinology, 2007
The glucocorticoid receptor (GR) is widely expressed in various tissues throughout the human body... more The glucocorticoid receptor (GR) is widely expressed in various tissues throughout the human body. At least three different 3 0 -splice variants of the GR have been reported: GR-a, which is functionally active; GR-b, which is a dominant negative inhibitor of GR-a function; and GR-P, which is thought to activate the function of GR-a. At least seven different variants for exon 1 exist, 1A-1F and 1H, each with its own promoter. In this study, we explored if tissue-specific splicing of the 3 0 -end variants of the GR is influenced by alternative promoter usage. cDNAs of different tissues and cell lines were used to investigate which part of transcripts carrying each of the three major variants for exons 1, 1A, 1B, or 1C, encodes for the splice variants GR-a, GR-b, and GR-P. Our data demonstrate that the expression of GR-a is preferentially regulated by promoter 1C and that for the expression of GR-P promoter 1B is predominantly used. This indicates that regulation of GR splice variants could partly occur through selective use of the multiple promoters, and that this is another way to sensitize cells and tissues to the different activities of the GR isoforms.
Journal of Endocrinology, 1996
This study describes the effects of litter size and acute suckling on the synthesis and release o... more This study describes the effects of litter size and acute suckling on the synthesis and release of hypothalamic TRH, as indirectly estimated by determination of hypothalamic prothyrotrophin-releasing hormone (proTRH) mRNA and median eminence TRH content. The effects of litter size (five or ten pups) were studied throughout lactation, while suckling-induced acute changes were analyzed on day 13 of lactation in dams with ten pups. In view of the enhanced adrenal activity during lactation and recent evidence that corticosteroids have negative effects on hypothalamic TRH, we also studied adrenalectomized (ADX) dams treated with corticosterone to maintain basal plasma corticosterone levels. In addition to an increased plasma level of prolactin (PRL), adrenal weight and plasma corticosterone increased, while plasma TSH, tri-iodothyronine (T3), thyroxine (T4) and free T4 (FT4) levels decreased during lactation. Litter size correlated positively with plasma PRL, adrenal weight and plasma corticosterone. No effect of litter size was observed on plasma T3, but rats with ten pups had lower plasma TSH, T4 and FT4 than rats with a five-pup litter. Compared with dioestrous rats, lactating rats showed an increased hypothalamic proTRH mRNA content on day 2, but not on days 8 and 15 of lactation. Median eminence TRH in lactating rats gradually increased until day 15 and decreased thereafter. Acute suckling, after a 6-h separation of mother and pups, rapidly increased plasma PRL and corticosterone in the mothers, but had no effects on plasma TSH and thyroid hormone levels. Hypothalamic proTRH mRNA increased twofold after 0.5 h of suckling, and then gradually returned to presuckling values after 6 h. Compared with sham-operated rats, corticosterone-substituted ADX rats with ten pups had increased plasma PRL and TSH, hypothalamic proTRH mRNA and pituitary TSH beta mRNA on day 15 of lactation. Moreover, while acute suckling did not enhance TSH release in sham-operated rats, it provoked not only PRL but also TSH release in corticosterone-substituted ADX dams. It is concluded that suckling exerts a rapid, positive effect on hypothalamic proTRH mRNA content. However, the concurrent enhanced adrenal activity has negative effects on hypothalamic proTRH gene expression resulting in a suppressed hypophysial-thyroid axis during lactation. While TRH appears to play a role in PRL release during the first days of lactation and during acute suckling, TRH seems not important in maintaining PRL secretion during continued suckling.
Journal of Endocrinology, 1996
The reduced thyroid activity during short-term starvation is associated with a lowered hypothalam... more The reduced thyroid activity during short-term starvation is associated with a lowered hypothalamic synthesis and secretion of TRH. However, little is known about the cause of the reduced thyroid function during prolonged malnutrition. We have therefore studied the effects of food reduction to one-third of normal (FR33) on the hypothalamus-pituitary-thyroid axis of male and female Wistar rats. After 3 weeks body weights of FR33 rats were almost 50% lower than those of controls. In both sexes, FR33 caused marked increases in serum corticosterone, and decreases in serum TSH, thyroxine (T4), free T4, tri-iodothyronine (T3) and free T3. While the free T3 fraction (FFT3) in serum decreased, the free T4 fraction (FFT4) tended to increase. Electrophoretic analysis indicated that decreased FFT3 was correlated with an increased thyroxine-binding globulin, while the increase in FFT4 seemed due to a decreased thyroxine-binding prealbumin binding capacity. Total RNA and proTRH mRNA in the hypothalamus were not affected by FR33. Median eminence and posterior pituitary TRH content tended to increase in FR33 rats, suggesting that hypothalamic TRH release is reduced in FR33 rats. Anterior pituitary TSH content was decreased by FR33 in both sexes, but pituitary TSH beta mRNA and TRH receptor status were not affected except for increased pituitary TSH beta mRNA in female FR33 rats. Although FR33 had no effect on pituitary weight, pituitary RNA and membrane protein content in FR33 rats were 50-70% lower than values in controls. In conclusion, prolonged food reduction suppresses the pituitary-thyroid axis in rats. In contrast to short-term food deprivation, the mechanism whereby serum TSH is suppressed does not appear to involve decreases in proTRH gene expression, but may include effects on pituitary mRNA translation. Our results further support the hypothesis that TSH release may be lowered by increased corticosterone secretion, although the mechanism of this effect may differ between acute starvation and prolonged food reduction.
Journal of Endocrinology, 1993
Direct effects of testosterone on gonadotrophins at the pituitary level were studied in intact an... more Direct effects of testosterone on gonadotrophins at the pituitary level were studied in intact and castrated immature (age 10 days) and mature (70 days) male rats. Gonadotrophin-releasing hormone action was blocked by treatment with a potent GnRH antagonist, Ac-D-pClPhe-D-pClPhe-D-Trp-Ser-Tyr-D-Arg-Leu-Arg-Pro-D-Ala-+ ++NH2CH3COOH (Ant; Organon 30276; 1.0 mg/kg body weight per day) injected subcutaneously. Silicone elastomer capsules were used for the testosterone treatment. Both treatments commenced on the day of orchiectomy and lasted for 7 days. In adult male rats Ant treatment suppressed serum testosterone from 9.5 +/- 2.5 (S.E.M.) nmol/l to below the limit of detection (< 0.10 nmol/l; P < 0.01), and the testosterone implants reversed the decrease. Treatment with Ant decreased the pituitary content of FSH-beta subunit mRNA in intact and orchiectomized rats to 14% of their respective controls (P < 0.01). These levels were increased to 80-81% of controls (not significant) in both groups by combined treatment with testosterone and Ant. Orchiectomy alone increased FSH-beta subunit mRNA by 202% (P < 0.01). In intact immature rats Ant treatment decreased the level of pituitary FSH-beta subunit mRNA to 21% (P < 0.01), and a partial recovery (P < 0.01) to 42% of controls was observed with combined Ant+testosterone treatment. In contrast, in orchiectomized immature rats, where ANT decreased FSH-beta subunit levels to 48% of controls (P < 0.01), testosterone was able to reverse these mRNA levels completely (114% of controls). No evidence for the direct pituitary effects of testosterone were found in the mRNA of the common alpha or LH-beta subunits. In adult rats, the testicular inhibin alpha and beta A subunit mRNA levels were increased (P < 0.01) by Ant+testosterone compared with Ant-treated animals, but there were no differences in serum immunoreactive inhibin between any of the uncastrated adult groups. In intact immature rats, Ant+testosterone treatment increased (P < 0.01) inhibin beta A subunit mRNA levels compared with controls and Ant-treated animals. Ant decreased the level fo peripheral inhibin immunoreactivity from 8.3 +/- 2.0 U/ml to 2.1 +/- 0.4 U/ml (P < 0.01) and testosterone reversed it to 5.8 +/- 0.6 U/ml (not significant). In conclusion, our observations indicated that testosterone is able to stimulate FSH gene expression and secretion directly in immature and adult rats, but the testosterone response is enhanced at both ages by orchiectomy, even more so in the immature rat.(ABSTRACT TRUNCATED AT 400 WORDS)
Journal of Endocrinology, 2012
ABSTRACT The antifungal agent ketoconazole is often used to suppress cortisol production in patie... more ABSTRACT The antifungal agent ketoconazole is often used to suppress cortisol production in patients with Cushing's syndrome. However, ketoconazole has serious side-effects and is hepatotoxic. Here, the in vitro effects of ketoconazole and fluconazole, which might be less toxic, on human adrenocortical steroidogenesis were compared.The effects on steroidogenesis were examined in primary cultures of nine human adrenocortical tissues and two human adrenocortical carcinoma cell lines. Moreover, the effects on mRNA expression levels of steroidogenic enzymes and cell growth were assessed.Ketoconazole significantly inhibited 11-deoxycortisol- (H295R cells; maximum inhibition 99%;EC50 0.73μM) and cortisol production (HAC15 cells;81%;EC50 0.26μM and primary cultures (mean EC50 0.75μM)). In cultures of normal adrenal cells, ketoconazole increased pregnenolone, progesterone and deoxycorticosterone levels, while concentrations of 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, DHEA and androstenedione decreased. Fluconazole also inhibited 11-deoxycortisol production in H295R cells (47%;only at 1mM) and cortisol production in HAC15 cells (maximum inhibition 55%;EC50 35μM) and primary cultures (mean EC50 67.7μM). In the cultures of normal adrenals, fluconazole suppressed corticosterone, 17-hydroxypregnenolone and androstenedione levels, whereas concentrations of progesterone, deoxycorticosterone and 11-deoxycortisol increased. Fluconazole(1mM) slightly increased STAR mRNA expression in both cell-lines.Neither compound affected mRNA levels of other steroidogenic enzymes or cell number.In conclusion, by inhibiting 11β-hydroxylase and 17-hydroxylase activity, pharmacological concentrations of fluconazole dose-dependently inhibit cortisol production in human adrenocortical cells in vitro. Although fluconazole seems less potent than ketoconazole, it might become an alternative for ketoconazole to control hypercortisolism in Cushing's syndrome. Furthermore, patients receiving fluconazole because of mycosis might be at risk for developing adrenocortical insufficiency.
Journal of Endocrinology, 1986
Inhibin was partially purified from bovine follicular fluid using chromatography on immobilized P... more Inhibin was partially purified from bovine follicular fluid using chromatography on immobilized Procion Red 3B and anion-exchange chromatography. Ovariectomized Texel ewes were immunized against the inhibin-containing fraction from the Procion Red 3B column and the immune response was subsequently boosted with similar fractions or with the preparation obtained from the anion-exchange column. The potencies of the resulting antisera were evaluated in an in-vitro bioassay system for estimating inhibin activity, using dispersed rat pituitary cells. The antisera were found to inhibit the bioactivity of inhibin preparations from ovarian follicular fluid of bovine, porcine, ovine or human origin, as well as inhibin activity in ovine testicular lymph and rete testis fluid, in culture media from rat granulosa and rat Sertoli cells and in homogenates of rat ovaries and testes. These results indicate that the inhibin molecules from several species contain a common bioactive moiety. The results also showed that the antiserum was more effective in neutralizing inhibin activity from ovarian than from testicular sources in both sheep and rat, indicating a sex-related difference in the inhibin molecules within a species.
Journal of Endocrinology, 1995
Recent evidence shows that thyrotrophin-releasing hormone (TRH) immunoreactivity in the rat anter... more Recent evidence shows that thyrotrophin-releasing hormone (TRH) immunoreactivity in the rat anterior pituitary gland is accounted for by the TRH-like tripeptide pyroglutamyl-glutamyl-prolineamide (pGlu-Glu-ProNH2, < EEP-NH2). The present study was undertaken to investigate further the regulation, localization and possible intrapituitary function of < EEP-NH2. Anterior pituitary levels of < EEP-NH2 were determined between days 5 and 35 of life, during the oestrous cycle and after treatment with the luteinizing hormone-releasing hormone (LHRH) antagonist Org 30276. Treatment of adult males with the LHRH antagonist either for 1 day (500 micrograms/100 g body weight) or for 5 days (50 micrograms/100 g body weight) reduced anterior pituitary < EEP-NH2 levels by 25-30% (P < 0.05 versus saline-treated controls). Anterior pituitary < EEP-NH2 increased between days 5 and 35 of life. In females, these levels were 2- to 3-fold higher (P < 0.05) than in males between days 15 and 25 after birth; these changes corresponded with the higher plasma follicle-stimulating hormone (FSH) levels in the female rats. After day 25, < EEP-NH2 levels in female rats decreased in parallel with a decrease in plasma FSH. Injections with the LHRH antagonist (500 micrograms/100 g body weight), starting on day 22 of life, led to reduced contents of < EEP-NH2 in the anterior pituitary gland of female rats on days 26 and 30 (55 and 35% decrease respectively). Levels of < EEP-NH2 in the anterior pituitary gland did not change significantly during the oestrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)