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.
Abstract: 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.
Publication Date: 1992-03-01 PubMed ID: 1537292DOI: 10.1210/endo.130.3.1537292Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research observes how treatment with different types of gonadotropins can alter the expression of the follicle-stimulating hormone (FSH) receptor in immature rats. The findings suggest that both up-regulation and down-regulation of FSH receptor gene expression are potentially induced by the hormone at different stages of ovarian follicle development.
Objective of the Research
- The study aims to understand the effects of different types of gonadotropins – pregnant mare’s serum gonadotropin (PMSG), human chorionic gonadotropin (hCG), and recombinant follicle-stimulating hormone (rFSH) – on the expression of the follicle-stimulating hormone (FSH) receptor in the ovaries of immature rats.
Methodology
- Researchers used a reverse transcription-polymerase chain reaction to acquire a rat FSH receptor cDNA fragment, and then produced a labeled cRNA probe to analyze the regulation of FSH receptor mRNA levels during different stages of follicular development, including maturation, ovulation, and luteinization.
- Northern blot analysis was performed on ovarian RNA with the FSH receptor probe, which revealed two main hybridization signals of 7.0 and 2.5 kilobases (kb), along with minor signals of 4.2 and 1.8 kb.
Results and Analysis
- Treatment of immature rats with PMSG, which induces follicular development, showed increased FSH receptor mRNA levels 24 hours after treatment, with a further increase at 52 hours. This was consistent with increased FSH binding.
- Administering an ovulatory dose of hCG decreased both FSH binding and receptor mRNA levels within 6 hours, with the most substantial decrease observed 24 hours after the hCG treatment.
- In the luteinized ovaries examined 3 and 5 days post-hCG treatment, the 7.0-kb FSH receptor mRNA increased again, although no corresponding elevation in FSH binding was detected.
- Experiments using rcFSH showed that this hormone alone can promote follicular growth and ovulation. In the experiments, immature hypophysectomized, estrogen-treated rats were implanted with an osmotic minipump delivering rcFSH for stimulating follicular growth, followed by a single injection of rcFSH to cause ovulation. After follicular growth stimulation with rcFSH, both FSH receptor binding and mRNA levels were increased. However, the ovulatory dose of rcFSH decreased FSH binding and receptor message levels within 12 hours.
Conclusion
- The research concluded that the regulation of ovarian FSH receptor content during follicular growth, ovulation, and luteinization is associated with similar changes in FSH receptor mRNA levels.
- Both up-regulation and down-regulation of FSH receptor gene expression can be induced by the hormone at different stages of follicle development.
Cite This Article
APA
LaPolt PS, Tilly JL, Aihara T, Nishimori K, Hsueh AJ.
(1992).
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.
Endocrinology, 130(3), 1289-1295.
https://doi.org/10.1210/endo.130.3.1537292 Publication
Researcher Affiliations
- Department of Gynecology and Obstetrics, Stanford University School of Medicine, California 94305-5317.
MeSH Terms
- Animals
- Blotting, Northern
- Chorionic Gonadotropin / pharmacology
- DNA / genetics
- DNA / metabolism
- Down-Regulation / drug effects
- Down-Regulation / genetics
- Female
- Follicle Stimulating Hormone / pharmacology
- Gene Expression Regulation / drug effects
- Gonadotropins / pharmacology
- Gonadotropins, Equine / pharmacology
- Iodine Radioisotopes
- Nucleic Acid Hybridization
- Ovary / chemistry
- Ovary / drug effects
- Ovary / ultrastructure
- Ovulation / drug effects
- Ovulation / genetics
- Polymerase Chain Reaction
- RNA Probes
- RNA, Messenger / analysis
- RNA, Messenger / genetics
- Rats
- Receptors, FSH / analysis
- Receptors, FSH / genetics
- Receptors, FSH / metabolism
- Recombinant Proteins / pharmacology
- Up-Regulation / drug effects
- Up-Regulation / genetics
Grant Funding
- HD-07252 / NICHD NIH HHS
- HD-23273 / NICHD NIH HHS
Citations
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