Gonadotropin-induced up- and down-regulation of ovarian follicle-stimulating hormone (FSH) receptor gene expression in immature rats: effects of pregnant mare's serum gonadotropin, human chorionic gonadotropin, and recombinant FSH.

The actions of gonadotropins on ovarian differentiation are associated with dynamic changes in gonadotropin receptor content, presumably due to modulation of receptor gene expression. The present studies used a reverse transcription-polymerase chain reaction to obtain a rat FSH receptor cDNA fragment, followed by synthesis of a labeled cRNA probe to examine the regulation of FSH receptor mRNA levels during follicular maturation, ovulation, and luteinization. Northern blot analysis of ovarian RNA with the FSH receptor probe revealed two predominant hybridization signals of 7.0 and 2.5 kilobases (kb) as well as minor signals of 4.2 and 1.8 kb. Treatment of immature rats with PMSG (10 IU) to induce follicular development resulted in increased FSH receptor mRNA levels 24 h after treatment, with a further increase at 52 h, coincident with increased [125I]FSH binding. Subsequent treatment with an ovulatory dose of hCG decreased FSH binding and receptor mRNA levels by 6 h, with a maximal inhibition at 24 h after hCG. In luteinized ovaries obtained 3 and 5 days after hCG treatment, the 7.0-kb FSH receptor mRNA increased again, but no concomitant elevation of [125I]FSH binding was detected. We recently demonstrated that FSH treatment alone is capable of inducing follicular growth and ovulation, thus providing a unique model to evaluate the effects of FSH on regulation of its receptor gene. Immature hypophysectomized estrogen-treated rats were implanted with an osmotic minipump delivering recombinant human FSH (rcFSH; 4 IU/day) to stimulate follicle growth, followed 52 h later with a single injection (20 IU) of rcFSH to induce ovulation. Stimulation of follicular growth with rcFSH increased both FSH receptor binding and mRNA levels. In contrast, the ovulatory dose of rcFSH decreased FSH binding and receptor message levels within 12 h. Thus, gonadotropin regulation of ovarian FSH receptor content during follicular growth, ovulation, and luteinization is associated with similar changes in FSH receptor message levels. Also, studies using rcFSH demonstrate that both up- and down-regulation of FSH receptor gene expression can be induced by the homologous hormone at different stages of follicle development.

[1]  J. Tilly,et al.  Hormonal regulation of follicle-stimulating hormone receptor messenger ribonucleic acid levels in cultured rat granulosa cells. , 1992, Endocrinology.

[2]  C. Strader,et al.  Leutropin/beta-adrenergic receptor chimeras bind choriogonadotropin and adrenergic ligands but are not expressed at the cell surface. , 1991, The Journal of biological chemistry.

[3]  A. Hsueh,et al.  Expression of human luteinizing hormone (LH) receptor: interaction with LH and chorionic gonadotropin from human but not equine, rat, and ovine species. , 1991, Molecular endocrinology.

[4]  M. Griswold,et al.  Expression of follicle-stimulating hormone receptor mRNA in rat testes and Sertoli cells. , 1991, Molecular endocrinology.

[5]  A. Hsueh,et al.  Ligand-induced down-regulation of testicular and ovarian luteinizing hormone (LH) receptors is preceded by tissue-specific inhibition of alternatively processed LH receptor transcripts. , 1991, Molecular endocrinology.

[6]  E. Borrelli,et al.  CREM gene: Use of alternative DNA-binding domains generates multiple antagonists of cAMP-induced transcription , 1991, Cell.

[7]  J. Richards,et al.  Hormonal regulation of luteinizing hormone/chorionic gonadotropin receptor mRNA in rat ovarian cells during follicular development and luteinization. , 1990, Molecular endocrinology.

[8]  A. Hsueh,et al.  Gonadotropin-induced up- and down-regulation of rat ovarian LH receptor message levels during follicular growth, ovulation and luteinization. , 1990, Endocrinology.

[9]  M. Parmentier,et al.  Molecular cloning of the thyrotropin receptor. , 1989, Science.

[10]  P. Sawchenko,et al.  Periovulatory Changes in the Expression of Inhibin α-, βA-, and βB-Subunits in Hormonally Induced Immature Female Rats , 1989 .

[11]  A. Shimizu,et al.  Kinetic study of internalization and degradation of 131I-labeled follicle-stimulating hormone in mouse Sertoli cells and its relevance to other systems. , 1989, The Journal of biological chemistry.

[12]  J. Garnier,et al.  Cloning and sequencing of porcine LH-hCG receptor cDNA: variants lacking transmembrane domain. , 1989, Science.

[13]  P. Seeburg,et al.  Lutropin-choriogonadotropin receptor: an unusual member of the G protein-coupled receptor family. , 1989, Science.

[14]  M. Matzuk,et al.  Expression of biologically active human follitropin in Chinese hamster ovary cells. , 1989, The Journal of biological chemistry.

[15]  J. Sanford,et al.  Endocytosis of follicle‐stimulating hormone by ovarian granulosa cells: Analysis of hormone processing and receptor dynamics , 1989, Journal of cellular physiology.

[16]  H. Shibai,et al.  Induction of follicle stimulating hormone receptor by erythroid differentiation factor on rat granulosa cell. , 1988, Biochemical and biophysical research communications.

[17]  M. Magnuson,et al.  Identification of basal and cyclic AMP regulatory elements in the promoter of the phosphoenolpyruvate carboxykinase gene , 1988, Molecular and cellular biology.

[18]  W. Roesler,et al.  Cyclic AMP and the induction of eukaryotic gene transcription. , 1988, The Journal of biological chemistry.

[19]  J. Richards,et al.  Changes in content of cytochrome P450(17)alpha, cytochrome P450scc, and 3-hydroxy-3-methylglutaryl CoA reductase in developing rat ovarian follicles and corpora lutea: correlation with theca cell steroidogenesis. , 1987, Biology of reproduction.

[20]  A. Hsueh,et al.  Homologous regulation of hormone receptors: luteinizing hormone increases its own receptors in cultured rat granulosa cells. , 1984, Endocrinology.

[21]  D. Melton,et al.  Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. , 1984, Nucleic acids research.

[22]  C. Auffray,et al.  Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. , 2005, European journal of biochemistry.

[23]  J. Richards,et al.  Granulosa cell desensitization: effects of gonadotropin on antral and preantral follicles. , 1980, Endocrinology.

[24]  J. Ireland,et al.  A previously underscribed role for luteinizing hormone (LH:hCG) on follicular cell differentiation. , 1978, Endocrinology.

[25]  C. Y. Lee,et al.  Follicle-stimulating hormone receptors in rat ovaries: decrease in numbers of binding sites associated with luteinization. , 1977, Endocrinology.

[26]  J. Richards,et al.  Regulation of gonadotropin receptors by luteinizing hormone in granulosa cells. , 1977, Endocrinology.

[27]  A. R. Midgley,et al.  Ovarian follicular development in the rat: hormone receptor regulation by estradiol, follicle stimulating hormone and luteinizing hormone. , 1976, Endocrinology.

[28]  K. Cheng.  Changes in rat ovaries of specific binding for LH, FSH and prolactin during the oestrous cycle and pregnancy. , 1976, Journal of reproduction and fertility.

[29]  L. Birnbaumer,et al.  Adenylyl cyclase activities in ovarian tissues. III. Regulation of responsiveness to LH, FSH, and PGE1 in the prepubertal, cycling, pregnant, and pseudopregnant rat. , 1976, Endocrinology.