Håkan Billig | University of Gothenburg (original) (raw)
Papers by Håkan Billig
Molecular and Cellular Endocrinology, Jul 1, 1989
It has been suggested that insulin-like growth factor-I (IGF-I) exerts paracrine or autocrine act... more It has been suggested that insulin-like growth factor-I (IGF-I) exerts paracrine or autocrine actions in the ovary and may play a role in the regulation of ovarian function. We have examined ovarian levels of IGF-I mRNA and IGF-I protein throughout the estrus cycle. The lowest levels of IGF-I mRNA were found on proestrus (12.00 h). The mRNA levels on estrus (12.00 h) were significantly (P < 0.05) higher than on proestrus. The correlation between the levels of IGF-I and IGF-I mRNA was linear and significant (r = 0.706; P-C 0.01). Our observations that the IGF-I gene expression and translation vary during the estrus cycle, with an increase between proestrus and es&us, suggest that the gonadotropin surge could be of importance for the regulation of IGF-I in vivo and that IGF-I may be involved in the cell proliferation and differentiation caused by these hormones.
Annals of the New York Academy of Sciences, Jun 1, 1991
Human granulosa cells, obtained either from natural or stimulated cycles, were cultured, and the ... more Human granulosa cells, obtained either from natural or stimulated cycles, were cultured, and the response to IGF-I and GH was analyzed. It was found that IGF-I alone stimulated thymidine incorporation in both types of granulosa cells. Furthermore, IGF-I alone and in combination with FSH or LH enhanced estradiol and progesterone production. In a limited series of experiments, GH in combination with FSH was found to stimulate steroidogenesis in granulosa cells obtained from natural, but not from stimulated, cycles.
Endocrinology, Mar 1, 1990
Atrial natriuretic peptide dose-dependently inhibited spontaneous phase and tonic activity of smo... more Atrial natriuretic peptide dose-dependently inhibited spontaneous phase and tonic activity of smooth muscle strips from the capsule of isolated bovine mesenteric lymph nodes. Pretreatment with L-NAME, diclofenac, and methylene blue had practically no effect on the peptideinduced relaxation responses. In contrast, glibenclamide signifi cantly reduced the inhibitory effect of atrial natriuretic peptide. We suppose that the NO-dependent and cyclooxygenase signaling pathways are not involved in implementation of the inhibitory effects of atrial natriuretic peptide. ATP-sensitive K +-channels of the smooth muscle cell membrane are the last component in the signaling pathway leading to relaxation of smooth muscles of the lymph node capsule caused by atrial natriuretic peptide; activation of these channels leads to membrane hyperpolarization and smooth muscle relaxation.
Endocrinology, 1998
High density lipoprotein (HDL) participates in reverse cholesterol transport and in the delivery ... more High density lipoprotein (HDL) participates in reverse cholesterol transport and in the delivery of cholesterol to steroid-producing tissues. Scavenger receptor class B type I (SR-BI) was recently shown to bind HDL and mediate internalization of its cholesterol content. We have cloned the rat homolog of this receptor, determined its chromosomal location, and examined its expression in rat tissues and in a model of follicular development, ovulation, and luteinization. The predicted protein contained two transmembrane domains, a leucine zipper motif, and a peroxisomal targeting sequence. The rat and human SR-BI genes were mapped to a region previously linked between rat and human chromosomes 12. SR-BI gene expression was detected in several rat tissues, with high levels in ovarian tissue, liver, and adrenal cortex, as determined by ribonuclease protection assay and in situ hybridization. A significant increase in SR-BI gene expression was detected in the late phase of corpus luteum formation, and transcripts were abundant in corpus luteum and in thecal cells at all stages of follicular development. In conclusion, the rat SR-BI complementary DNA predicted a protein with several conserved motifs, including a putative leucine zipper and a peroxisomal targeting sequence. The chromosomal locations of the rat and human SR-BI homologs suggest that this gene is a new member of a previously reported, conserved synteny group. SR-BI gene expression was high in steroid-producing tissues and in the liver, consistent with a role of this receptor in the uptake of HDL cholesterol. (Endocrinology 139: 72-80, 1998) Materials and Methods Animals The use of animals in this study was approved by the local ethics committee for animal care and use (Göteborg, Sweden). Female Sprague-Dawley rats (Alab, Stockholm, Sweden) were housed under standardized environmental conditions with constant temperature (24-26 C), humidity (50-60%), and an artificial 14-h light and 10-h dark cycle. The animals had free access to water and pelleted food. To induce
Endocrinology, Oct 1, 2000
There are indications that PRL may exert important metabolic actions on adipose tissue in differe... more There are indications that PRL may exert important metabolic actions on adipose tissue in different species. However, with the exception of birds, the receptor has not been identified in white adipose tissue. The present study was designed to examine the possible expression and regulation of the PRL receptor (PRLR) in mouse adipose tissue. The long PRLR messenger RNA (mRNA) splice form (L-PRLR) and two short splice forms (S2-and S3-PRLR) were detected in mouse adipose tissue by RT-PCR. Furthermore, L-PRLR mRNA was detected by ribonuclease protection assay. Immunoreactive PRLR with a relative molecular mass of 95,000 was revealed by immunoblotting. Furthermore, L-PRLR mRNA expression was demonstrated in primary isolated adipocytes. In mouse adipose tissue, the level of L-PRLR mRNA expression increased 2.3-fold during lactation compared with those in virgin and pregnant mice. In contrast, in the liver the expression of L-PRLR increased 3.4-fold during pregnancy compared with those in virgin and lactating mice. When comparing the levels of L-PRLR expression in virgin female and male mice, no difference was detected in adipose tissue. However, in virgin female liver the expression was 4.5-fold higher than that in male liver. As PRL up-regulates its own receptor in some tissues, we analyzed L-PRLR expression in PRL-transgenic female and male mice. In PRLtransgenic mice L-PRLR expression was significantly increased in both adipose tissue (1.4-fold in females and 2.4-fold in males) and liver (1.9-fold in females and 2.7-fold in males) compared with that in control mice. Furthermore, in female PRL-transgenic mice retroperitoneal adipose tissue was decreased in weight compared with that in control mice. However, no difference was detected when comparing the masses of parametrial adipose tissue. Our results suggest a direct role for PRL, mediated by PRLR, in modulating physiological events in adipose tissue.
Endocrinology, Nov 1, 1993
Biology of Reproduction, Jun 1, 1989
The distribution of insulin-like growth factor I (JGF-J; somatomedin C) was mapped in testes of d... more The distribution of insulin-like growth factor I (JGF-J; somatomedin C) was mapped in testes of different aged rats by using isninunohistochemical techniques. The antiserum used, K 624, has been demonstrated to be specific for human IGF-I, as defined by several criteria. Antibodies to the MI subunit of ribonucleotide reductase, a key enzyme in DNA synthesis, were used to visualize rneiotic and mitotic cells. Cytoplasmic IGF-I-like immunoreactivity as demonstrable during the first two postnatal weeks in spermatogenic cells, in Sertoli cells, and in Leydig cells. The IGF-I-like immunoreactivity decreased in the Sertoli and Leydig cells during the third and fourth postnatal weeks, and in adult rats, only sperinatogenic cells showed IGF-I-like immunoreactivity. In mature rat testes, the spermatocytes were strongly immunoreactive. During puberty and adulthood, the spermatogonia expressed subunit Ml ribonucleotide reducta.se immunoreactivily, whereas no IGF-I-like i,nmunoreactivity could be detected. No e.xu'acel!ular immunoreactivity was observed. We propose that IGF-1 and/or IGF-1-like substances, possibly formed by primary spermatocytes, are likely to be involved in differentiation processes, but not in the initiation of cell proliferation in adult testes. The autocrine and/or paracrine action of IGF-I and/or IGF-1-like substances may thus have different action in developing testes than in adult testes. Our results do, however, not allow firm statements about whether IGF-I and related substances exert their actions on Sertoli cells or spermatogenic cells.
Gynecological Endocrinology, 1996
Biology of Reproduction, Apr 1, 1983
The effect of an agonistic gonadotropin releasing hormone (GnRH)-analog (D-Ala' ,des-Gly'#{176}-N... more The effect of an agonistic gonadotropin releasing hormone (GnRH)-analog (D-Ala' ,des-Gly'#{176}-NH3-GnRH-ethylamide, GnRHa) on granulosa cell steroidogenesis in the presence or absence of follicle-stimulating hormone (FSH) or luteinizing hormone (LH) was studied. Granulosa
Gamete Research, 1983
... Hgkan Billig, Torbjorn Hillensjo, Alexander Tsafriri, Claes Magnusson, and Angela Brodie ... ... more ... Hgkan Billig, Torbjorn Hillensjo, Alexander Tsafriri, Claes Magnusson, and Angela Brodie ... The effects reported are, however, conflicting and both inhibitory and stimulatory effects of exogenous steroids on isolated oocytes have been found [eg , Robertson and Baker, 1969; Bae ...
Molecular and Cellular Endocrinology, May 1, 1991
Endocrinology, Jun 1, 1999
Scavenger receptor class B type I (SR-BI) mediates the selective uptake of high density lipoprote... more Scavenger receptor class B type I (SR-BI) mediates the selective uptake of high density lipoprotein cholesterol. SR-BI is expressed at high levels in the ovary, indicating that it plays a role in the delivery of cholesterol as substrate for steroid hormone production. However, SR-BI also binds anionic phospholipids with high affinity and could therefore be involved in the recognition of apoptotic cells. In this study we have characterized the expression of SR-BI in rat ovarian follicles undergoing atresia. Atretic follicles with cells undergoing apoptosis were identified by in situ DNA end labeling, and SR-BI expression was determined by in situ hybridization and immunohistochemistry. SR-BI was expressed in thecal cells at all stages of follicular development, including atretic follicles, and in corpus luteum. Isolated apoptotic granulosa cells (but not viable granulosa cells) bound annexin V, indicating that they display anionic phospholipids on the cell
Endocrinology, Jun 1, 1997
Progression of preantral follicle development is essential to further follicle maturation and ovu... more Progression of preantral follicle development is essential to further follicle maturation and ovulation, but there are few models for studying the regulation of preantral follicle survival and growth. We have evaluated preantral follicle survival in vivo and in vitro, and have developed a serum-free rat follicle culture system that can be used to characterize the regulation of preantral follicle growth and differentiation. Analysis of ovarian cell DNA fragmentation during the first wave of follicle growth in the infantile rat indicated negligible apoptosis up to day 16 of age. However, a major increase in apoptosis was found by day 18, a time point associated with the appearance of large antral follicles. In situ analysis confirmed that apoptotic DNA fragments were limited to antral follicles. Culture of individual preantral follicles mechanically dissected from ovaries of 12-or 14-day-old rats in serum-free conditions led to major increases in follicle cell apoptosis, similar to that seen in cultures of antral and preovulatory follicles. In contrast to antral and preovulatory follicles, treatment of preantral follicles with gonadotropins or cAMP analogs did not prevent apoptosis. However, treatment with 8-bromo-cGMP or 10% serum sup
Biology of Reproduction, Nov 1, 1994
Although surgical induction of cryptorchidism in the rat is known to cause infertility due to dis... more Although surgical induction of cryptorchidism in the rat is known to cause infertility due to disruption of spermatogenesis, the exact cellular mechanism responsible for the degenerative changes in cryptorchid testes is unclear. Using a sensitive autoradiographic method for the detection of apoptotic DNA fragmentation, we have investigated the effect of experimentally induced cryptorchidism on apoptotic cell death in testes of immature rats. Bilateral or unilateral cryptorchidism decreased the weight of affected testes within 4 days; these decreases (24-27%) became significant (p < 0.05) at 7 days after the operation. Testes of sham-operated animals contained predominantly high molecular weight DNA (> 15 kb), whereas DNA cleavage into low molecular weight ladders characteristic of apoptosis was increased by induction of bilateral cryptorchidism in a time-dependent manner, i.e., 2.0-, 2.8-, and 4.2-fold (p < 0.05) at 2, 4, and 7 days after operation, respectively. In unilaterally cryptorchid animals, sham-operated testes also contained predominantly high molecular weight DNA, whereas induction of cryptorchidism of the contralateral testes increased DNA cleavage into low molecular weight fragments 3.0-, 2.8-, and 3.9-fold (p < 0.05) at 2, 4, and 7 days after the operation, respectively. In situ analysis of DNA fragmentation in testes of unilaterally cryptorchid rats at 7 days after the operation indicated that germ cells, mainly primary spermatocytes, were affected and that the percentage of seminiferous tubules containing labeled cells increased in the operated testis as compared to the contralateral control in the same animal. Furthermore, according to radioligand receptor analysis, specific ['251]-hCG binding to cryptorchid testes was not affected at 2 and 4 days after the operation but was significantly (p < 0.05) decreased (32-35%), in relation to values in sham-operated testes in both bilaterally and unilaterally cryptorchid animals, at 7 days after surgery. In addition, testis ['25I]-hCG binding per milligram protein was not affected by the induction of bilateral or unilateral cryptorchidism throughout the 7 days of the experiment. Our data indicate that cryptorchidism-induced testis cell degeneration is mediated by apoptosis probably as the result of increases in testis temperature, leading to delayed decreases in LH receptors of Leydig cells. Although apoptotic cell death induced by bilateral cryptorchidism might be affected by changes in systemic factors, the increase of apoptosis in male germ cells after unilateral cryptorchidism is presumably regulated by local testicular factors. Experimentally induced cryptorchidism provides a useful model for study of the role of elevated temperature on testis cell apoptosis.
ABSTRACT This report is a follow up on the junior researcher programme as a funding instrument at... more ABSTRACT This report is a follow up on the junior researcher programme as a funding instrument at the Swedish Research Council, Medicine. The evaluation is based on a survey sent to researchers who applied for junior research positions within medicine in the mid and late 1990s, examining their careers retro-spectively. The conclusions are that those appointed a junior research position from the Scientific Council of Medicine are frequently found to pursue successful scientific careers. Hence, the resources allocated for junior research positions to boost development of future scientific leaders in medical research have been well-invested. However, there are differences for men and women, most likely reflecting a combination of factors including professional and private life. Follow-up and evaluation of junior research positions from the Swedish Research Council, Medicine Klarabergsviadukten 82 | Box 1035 | SE-101 38 Stockholm | SWEDEN | Tel + 46-8-546 44 000 | vetenskapsradet@vr.se | www.vr.se The Swedish Research Council is a government agency that provides funding for basic research of the highest scientific quality in all disciplinary domains. Besides research funding, the agency works with strategy, analysis, and research communication. The objective is for Sweden to be a leading research nation.
Molecular Reproduction and Development, 2007
II Distribution and hormonal regulation of membrane progesterone receptors beta and gamma in cili... more II Distribution and hormonal regulation of membrane progesterone receptors beta and gamma in ciliated epithelial cells of mouse and human fallopian tubes
European journal of endocrinology, 1984
The effect of a GnRH analogue ((D-Ala6, des-Gly10-NH2)-GnRH-ethylamide,GnRHa) on granulosa and cu... more The effect of a GnRH analogue ((D-Ala6, des-Gly10-NH2)-GnRH-ethylamide,GnRHa) on granulosa and cumulus cell glycolysis in presence or absence of FSH was studied. Cumulus complexes and granulosa cells from PMSG-treated rats were cultured in Eagle's minimal essential medium (MEM) for a period of 72 h. Media were changed at 24 and 48 h and lactate content was assayed by fluorimetry. GnRHa alone stimulated lactate production in granulosa cells. GnRH combined with FSH increased lactate production in granulosa cells during the 0\p=n-\24h period and decreased it during the 48\p=n-\72 h period as compared to FSH alone. GnRHa did not stimulate lactate production in cumulus complexes during 72 h culture in MEM, while FSH did. In a less complex culture medium,
Molecular and Cellular Endocrinology, Apr 1, 1988
Effects of adenosine analogues on adenylate cyclase activity in preovulatory rat ovarian membrane... more Effects of adenosine analogues on adenylate cyclase activity in preovulatory rat ovarian membranes were studied. Adenosine analogues stimulated adenylate cyclase activity in the following rank order of potency: NECA (5'-(N-ethyl)carboxamidoadenosine) > 2-chloroadenosine > N6-(R-phenylisopropyl)adenosine > N6-(S-phenylisopropyl)adenosine. The apparent EC,, for NECA was 0.28 PM. The adenosine receptor antagonist 8-phenyltheophylline (10 PM) displaced the dose-response curve for NECA to the right, increasing the EC,,, for NECA about one order of magnitude. NECA also additively increased maximally FSH-stimulated adenylate cyclase activity. These results suggest that adenosine stimulates adenylate cyclase in rat ovarian membranes via adenosine receptors of the A, type.
Molecular and Cellular Endocrinology, Jul 1, 1989
It has been suggested that insulin-like growth factor-I (IGF-I) exerts paracrine or autocrine act... more It has been suggested that insulin-like growth factor-I (IGF-I) exerts paracrine or autocrine actions in the ovary and may play a role in the regulation of ovarian function. We have examined ovarian levels of IGF-I mRNA and IGF-I protein throughout the estrus cycle. The lowest levels of IGF-I mRNA were found on proestrus (12.00 h). The mRNA levels on estrus (12.00 h) were significantly (P < 0.05) higher than on proestrus. The correlation between the levels of IGF-I and IGF-I mRNA was linear and significant (r = 0.706; P-C 0.01). Our observations that the IGF-I gene expression and translation vary during the estrus cycle, with an increase between proestrus and es&us, suggest that the gonadotropin surge could be of importance for the regulation of IGF-I in vivo and that IGF-I may be involved in the cell proliferation and differentiation caused by these hormones.
Annals of the New York Academy of Sciences, Jun 1, 1991
Human granulosa cells, obtained either from natural or stimulated cycles, were cultured, and the ... more Human granulosa cells, obtained either from natural or stimulated cycles, were cultured, and the response to IGF-I and GH was analyzed. It was found that IGF-I alone stimulated thymidine incorporation in both types of granulosa cells. Furthermore, IGF-I alone and in combination with FSH or LH enhanced estradiol and progesterone production. In a limited series of experiments, GH in combination with FSH was found to stimulate steroidogenesis in granulosa cells obtained from natural, but not from stimulated, cycles.
Endocrinology, Mar 1, 1990
Atrial natriuretic peptide dose-dependently inhibited spontaneous phase and tonic activity of smo... more Atrial natriuretic peptide dose-dependently inhibited spontaneous phase and tonic activity of smooth muscle strips from the capsule of isolated bovine mesenteric lymph nodes. Pretreatment with L-NAME, diclofenac, and methylene blue had practically no effect on the peptideinduced relaxation responses. In contrast, glibenclamide signifi cantly reduced the inhibitory effect of atrial natriuretic peptide. We suppose that the NO-dependent and cyclooxygenase signaling pathways are not involved in implementation of the inhibitory effects of atrial natriuretic peptide. ATP-sensitive K +-channels of the smooth muscle cell membrane are the last component in the signaling pathway leading to relaxation of smooth muscles of the lymph node capsule caused by atrial natriuretic peptide; activation of these channels leads to membrane hyperpolarization and smooth muscle relaxation.
Endocrinology, 1998
High density lipoprotein (HDL) participates in reverse cholesterol transport and in the delivery ... more High density lipoprotein (HDL) participates in reverse cholesterol transport and in the delivery of cholesterol to steroid-producing tissues. Scavenger receptor class B type I (SR-BI) was recently shown to bind HDL and mediate internalization of its cholesterol content. We have cloned the rat homolog of this receptor, determined its chromosomal location, and examined its expression in rat tissues and in a model of follicular development, ovulation, and luteinization. The predicted protein contained two transmembrane domains, a leucine zipper motif, and a peroxisomal targeting sequence. The rat and human SR-BI genes were mapped to a region previously linked between rat and human chromosomes 12. SR-BI gene expression was detected in several rat tissues, with high levels in ovarian tissue, liver, and adrenal cortex, as determined by ribonuclease protection assay and in situ hybridization. A significant increase in SR-BI gene expression was detected in the late phase of corpus luteum formation, and transcripts were abundant in corpus luteum and in thecal cells at all stages of follicular development. In conclusion, the rat SR-BI complementary DNA predicted a protein with several conserved motifs, including a putative leucine zipper and a peroxisomal targeting sequence. The chromosomal locations of the rat and human SR-BI homologs suggest that this gene is a new member of a previously reported, conserved synteny group. SR-BI gene expression was high in steroid-producing tissues and in the liver, consistent with a role of this receptor in the uptake of HDL cholesterol. (Endocrinology 139: 72-80, 1998) Materials and Methods Animals The use of animals in this study was approved by the local ethics committee for animal care and use (Göteborg, Sweden). Female Sprague-Dawley rats (Alab, Stockholm, Sweden) were housed under standardized environmental conditions with constant temperature (24-26 C), humidity (50-60%), and an artificial 14-h light and 10-h dark cycle. The animals had free access to water and pelleted food. To induce
Endocrinology, Oct 1, 2000
There are indications that PRL may exert important metabolic actions on adipose tissue in differe... more There are indications that PRL may exert important metabolic actions on adipose tissue in different species. However, with the exception of birds, the receptor has not been identified in white adipose tissue. The present study was designed to examine the possible expression and regulation of the PRL receptor (PRLR) in mouse adipose tissue. The long PRLR messenger RNA (mRNA) splice form (L-PRLR) and two short splice forms (S2-and S3-PRLR) were detected in mouse adipose tissue by RT-PCR. Furthermore, L-PRLR mRNA was detected by ribonuclease protection assay. Immunoreactive PRLR with a relative molecular mass of 95,000 was revealed by immunoblotting. Furthermore, L-PRLR mRNA expression was demonstrated in primary isolated adipocytes. In mouse adipose tissue, the level of L-PRLR mRNA expression increased 2.3-fold during lactation compared with those in virgin and pregnant mice. In contrast, in the liver the expression of L-PRLR increased 3.4-fold during pregnancy compared with those in virgin and lactating mice. When comparing the levels of L-PRLR expression in virgin female and male mice, no difference was detected in adipose tissue. However, in virgin female liver the expression was 4.5-fold higher than that in male liver. As PRL up-regulates its own receptor in some tissues, we analyzed L-PRLR expression in PRL-transgenic female and male mice. In PRLtransgenic mice L-PRLR expression was significantly increased in both adipose tissue (1.4-fold in females and 2.4-fold in males) and liver (1.9-fold in females and 2.7-fold in males) compared with that in control mice. Furthermore, in female PRL-transgenic mice retroperitoneal adipose tissue was decreased in weight compared with that in control mice. However, no difference was detected when comparing the masses of parametrial adipose tissue. Our results suggest a direct role for PRL, mediated by PRLR, in modulating physiological events in adipose tissue.
Endocrinology, Nov 1, 1993
Biology of Reproduction, Jun 1, 1989
The distribution of insulin-like growth factor I (JGF-J; somatomedin C) was mapped in testes of d... more The distribution of insulin-like growth factor I (JGF-J; somatomedin C) was mapped in testes of different aged rats by using isninunohistochemical techniques. The antiserum used, K 624, has been demonstrated to be specific for human IGF-I, as defined by several criteria. Antibodies to the MI subunit of ribonucleotide reductase, a key enzyme in DNA synthesis, were used to visualize rneiotic and mitotic cells. Cytoplasmic IGF-I-like immunoreactivity as demonstrable during the first two postnatal weeks in spermatogenic cells, in Sertoli cells, and in Leydig cells. The IGF-I-like immunoreactivity decreased in the Sertoli and Leydig cells during the third and fourth postnatal weeks, and in adult rats, only sperinatogenic cells showed IGF-I-like immunoreactivity. In mature rat testes, the spermatocytes were strongly immunoreactive. During puberty and adulthood, the spermatogonia expressed subunit Ml ribonucleotide reducta.se immunoreactivily, whereas no IGF-I-like i,nmunoreactivity could be detected. No e.xu'acel!ular immunoreactivity was observed. We propose that IGF-1 and/or IGF-1-like substances, possibly formed by primary spermatocytes, are likely to be involved in differentiation processes, but not in the initiation of cell proliferation in adult testes. The autocrine and/or paracrine action of IGF-I and/or IGF-1-like substances may thus have different action in developing testes than in adult testes. Our results do, however, not allow firm statements about whether IGF-I and related substances exert their actions on Sertoli cells or spermatogenic cells.
Gynecological Endocrinology, 1996
Biology of Reproduction, Apr 1, 1983
The effect of an agonistic gonadotropin releasing hormone (GnRH)-analog (D-Ala' ,des-Gly'#{176}-N... more The effect of an agonistic gonadotropin releasing hormone (GnRH)-analog (D-Ala' ,des-Gly'#{176}-NH3-GnRH-ethylamide, GnRHa) on granulosa cell steroidogenesis in the presence or absence of follicle-stimulating hormone (FSH) or luteinizing hormone (LH) was studied. Granulosa
Gamete Research, 1983
... Hgkan Billig, Torbjorn Hillensjo, Alexander Tsafriri, Claes Magnusson, and Angela Brodie ... ... more ... Hgkan Billig, Torbjorn Hillensjo, Alexander Tsafriri, Claes Magnusson, and Angela Brodie ... The effects reported are, however, conflicting and both inhibitory and stimulatory effects of exogenous steroids on isolated oocytes have been found [eg , Robertson and Baker, 1969; Bae ...
Molecular and Cellular Endocrinology, May 1, 1991
Endocrinology, Jun 1, 1999
Scavenger receptor class B type I (SR-BI) mediates the selective uptake of high density lipoprote... more Scavenger receptor class B type I (SR-BI) mediates the selective uptake of high density lipoprotein cholesterol. SR-BI is expressed at high levels in the ovary, indicating that it plays a role in the delivery of cholesterol as substrate for steroid hormone production. However, SR-BI also binds anionic phospholipids with high affinity and could therefore be involved in the recognition of apoptotic cells. In this study we have characterized the expression of SR-BI in rat ovarian follicles undergoing atresia. Atretic follicles with cells undergoing apoptosis were identified by in situ DNA end labeling, and SR-BI expression was determined by in situ hybridization and immunohistochemistry. SR-BI was expressed in thecal cells at all stages of follicular development, including atretic follicles, and in corpus luteum. Isolated apoptotic granulosa cells (but not viable granulosa cells) bound annexin V, indicating that they display anionic phospholipids on the cell
Endocrinology, Jun 1, 1997
Progression of preantral follicle development is essential to further follicle maturation and ovu... more Progression of preantral follicle development is essential to further follicle maturation and ovulation, but there are few models for studying the regulation of preantral follicle survival and growth. We have evaluated preantral follicle survival in vivo and in vitro, and have developed a serum-free rat follicle culture system that can be used to characterize the regulation of preantral follicle growth and differentiation. Analysis of ovarian cell DNA fragmentation during the first wave of follicle growth in the infantile rat indicated negligible apoptosis up to day 16 of age. However, a major increase in apoptosis was found by day 18, a time point associated with the appearance of large antral follicles. In situ analysis confirmed that apoptotic DNA fragments were limited to antral follicles. Culture of individual preantral follicles mechanically dissected from ovaries of 12-or 14-day-old rats in serum-free conditions led to major increases in follicle cell apoptosis, similar to that seen in cultures of antral and preovulatory follicles. In contrast to antral and preovulatory follicles, treatment of preantral follicles with gonadotropins or cAMP analogs did not prevent apoptosis. However, treatment with 8-bromo-cGMP or 10% serum sup
Biology of Reproduction, Nov 1, 1994
Although surgical induction of cryptorchidism in the rat is known to cause infertility due to dis... more Although surgical induction of cryptorchidism in the rat is known to cause infertility due to disruption of spermatogenesis, the exact cellular mechanism responsible for the degenerative changes in cryptorchid testes is unclear. Using a sensitive autoradiographic method for the detection of apoptotic DNA fragmentation, we have investigated the effect of experimentally induced cryptorchidism on apoptotic cell death in testes of immature rats. Bilateral or unilateral cryptorchidism decreased the weight of affected testes within 4 days; these decreases (24-27%) became significant (p < 0.05) at 7 days after the operation. Testes of sham-operated animals contained predominantly high molecular weight DNA (> 15 kb), whereas DNA cleavage into low molecular weight ladders characteristic of apoptosis was increased by induction of bilateral cryptorchidism in a time-dependent manner, i.e., 2.0-, 2.8-, and 4.2-fold (p < 0.05) at 2, 4, and 7 days after operation, respectively. In unilaterally cryptorchid animals, sham-operated testes also contained predominantly high molecular weight DNA, whereas induction of cryptorchidism of the contralateral testes increased DNA cleavage into low molecular weight fragments 3.0-, 2.8-, and 3.9-fold (p < 0.05) at 2, 4, and 7 days after the operation, respectively. In situ analysis of DNA fragmentation in testes of unilaterally cryptorchid rats at 7 days after the operation indicated that germ cells, mainly primary spermatocytes, were affected and that the percentage of seminiferous tubules containing labeled cells increased in the operated testis as compared to the contralateral control in the same animal. Furthermore, according to radioligand receptor analysis, specific ['251]-hCG binding to cryptorchid testes was not affected at 2 and 4 days after the operation but was significantly (p < 0.05) decreased (32-35%), in relation to values in sham-operated testes in both bilaterally and unilaterally cryptorchid animals, at 7 days after surgery. In addition, testis ['25I]-hCG binding per milligram protein was not affected by the induction of bilateral or unilateral cryptorchidism throughout the 7 days of the experiment. Our data indicate that cryptorchidism-induced testis cell degeneration is mediated by apoptosis probably as the result of increases in testis temperature, leading to delayed decreases in LH receptors of Leydig cells. Although apoptotic cell death induced by bilateral cryptorchidism might be affected by changes in systemic factors, the increase of apoptosis in male germ cells after unilateral cryptorchidism is presumably regulated by local testicular factors. Experimentally induced cryptorchidism provides a useful model for study of the role of elevated temperature on testis cell apoptosis.
ABSTRACT This report is a follow up on the junior researcher programme as a funding instrument at... more ABSTRACT This report is a follow up on the junior researcher programme as a funding instrument at the Swedish Research Council, Medicine. The evaluation is based on a survey sent to researchers who applied for junior research positions within medicine in the mid and late 1990s, examining their careers retro-spectively. The conclusions are that those appointed a junior research position from the Scientific Council of Medicine are frequently found to pursue successful scientific careers. Hence, the resources allocated for junior research positions to boost development of future scientific leaders in medical research have been well-invested. However, there are differences for men and women, most likely reflecting a combination of factors including professional and private life. Follow-up and evaluation of junior research positions from the Swedish Research Council, Medicine Klarabergsviadukten 82 | Box 1035 | SE-101 38 Stockholm | SWEDEN | Tel + 46-8-546 44 000 | vetenskapsradet@vr.se | www.vr.se The Swedish Research Council is a government agency that provides funding for basic research of the highest scientific quality in all disciplinary domains. Besides research funding, the agency works with strategy, analysis, and research communication. The objective is for Sweden to be a leading research nation.
Molecular Reproduction and Development, 2007
II Distribution and hormonal regulation of membrane progesterone receptors beta and gamma in cili... more II Distribution and hormonal regulation of membrane progesterone receptors beta and gamma in ciliated epithelial cells of mouse and human fallopian tubes
European journal of endocrinology, 1984
The effect of a GnRH analogue ((D-Ala6, des-Gly10-NH2)-GnRH-ethylamide,GnRHa) on granulosa and cu... more The effect of a GnRH analogue ((D-Ala6, des-Gly10-NH2)-GnRH-ethylamide,GnRHa) on granulosa and cumulus cell glycolysis in presence or absence of FSH was studied. Cumulus complexes and granulosa cells from PMSG-treated rats were cultured in Eagle's minimal essential medium (MEM) for a period of 72 h. Media were changed at 24 and 48 h and lactate content was assayed by fluorimetry. GnRHa alone stimulated lactate production in granulosa cells. GnRH combined with FSH increased lactate production in granulosa cells during the 0\p=n-\24h period and decreased it during the 48\p=n-\72 h period as compared to FSH alone. GnRHa did not stimulate lactate production in cumulus complexes during 72 h culture in MEM, while FSH did. In a less complex culture medium,
Molecular and Cellular Endocrinology, Apr 1, 1988
Effects of adenosine analogues on adenylate cyclase activity in preovulatory rat ovarian membrane... more Effects of adenosine analogues on adenylate cyclase activity in preovulatory rat ovarian membranes were studied. Adenosine analogues stimulated adenylate cyclase activity in the following rank order of potency: NECA (5'-(N-ethyl)carboxamidoadenosine) > 2-chloroadenosine > N6-(R-phenylisopropyl)adenosine > N6-(S-phenylisopropyl)adenosine. The apparent EC,, for NECA was 0.28 PM. The adenosine receptor antagonist 8-phenyltheophylline (10 PM) displaced the dose-response curve for NECA to the right, increasing the EC,,, for NECA about one order of magnitude. NECA also additively increased maximally FSH-stimulated adenylate cyclase activity. These results suggest that adenosine stimulates adenylate cyclase in rat ovarian membranes via adenosine receptors of the A, type.