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.
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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
Department of Gynecology and Obstetrics, Stanford University School of Medicine, California 94305-5317.
Tilly, J L
Aihara, T
Nishimori, K
Hsueh, A J
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
This article has been cited 20 times.
Yang B, Gong J, Jing J, Hao Y, Li S, Liu G, Feng Z, Zhao G. Effects of Zinc Methionine Hydroxy Analog Chelate on Laying Performance, Serum Hormone Levels, and Expression of Reproductive Axis Related Genes in Aged Broiler Breeders. Front Vet Sci 2022;9:918283.
Benammar A, Fanchin R, Filali-Baba M, Vialard F, Fossard C, Vandame J, Pirtea P, Racowsky C, Ayoubi JM, Poulain M. Utilization of in vitro maturation in cases with a FSH receptor mutation. J Assist Reprod Genet 2021 Jun;38(6):1311-1321.
Kandasamy M, Radhakrishnan RK, Poornimai Abirami GP, Roshan SA, Yesudhas A, Balamuthu K, Prahalathan C, Shanmugaapriya S, Moorthy A, Essa MM, Anusuyadevi M. Possible Existence of the Hypothalamic-Pituitary-Hippocampal (HPH) Axis: A Reciprocal Relationship Between Hippocampal Specific Neuroestradiol Synthesis and Neuroblastosis in Ageing Brains with Special Reference to Menopause and Neurocognitive Disorders. Neurochem Res 2019 Aug;44(8):1781-1795.
Matvere A, Teino I, Varik I, Kuuse S, Tiido T, Kristjuhan A, Maimets T. FSH/LH-Dependent Upregulation of Ahr in Murine Granulosa Cells Is Controlled by PKA Signaling and Involves Epigenetic Regulation. Int J Mol Sci 2019 Jun 23;20(12).
Babayev E, Lalioti MD, Favero F, Seli E. Cross-Talk Between FSH and Endoplasmic Reticulum Stress: A Mutually Suppressive Relationship. Reprod Sci 2016 Mar;23(3):352-64.
Coskun S, Otu HH, Awartani KA, Al-Alwan LA, Al-Hassan S, Al-Mayman H, Kaya N, Inan MS. Gene expression profiling of granulosa cells from PCOS patients following varying doses of human chorionic gonadotropin. J Assist Reprod Genet 2013 Mar;30(3):341-52.
Jeppesen JV, Kristensen SG, Nielsen ME, Humaidan P, Dal Canto M, Fadini R, Schmidt KT, Ernst E, Yding Andersen C. LH-receptor gene expression in human granulosa and cumulus cells from antral and preovulatory follicles. J Clin Endocrinol Metab 2012 Aug;97(8):E1524-31.
Parrish EM, Siletz A, Xu M, Woodruff TK, Shea LD. Gene expression in mouse ovarian follicle development in vivo versus an ex vivo alginate culture system. Reproduction 2011 Aug;142(2):309-18.
Mancinelli R, Onori P, Demorrow S, Francis H, Glaser S, Franchitto A, Carpino G, Alpini G, Gaudio E. Role of sex hormones in the modulation of cholangiocyte function. World J Gastrointest Pathophysiol 2010 Jun 15;1(2):50-62.
Cannon JG, Cortez-Cooper M, Meaders E, Stallings J, Haddow S, Kraj B, Sloan G, Mulloy A. Follicle-stimulating hormone, interleukin-1, and bone density in adult women. Am J Physiol Regul Integr Comp Physiol 2010 Mar;298(3):R790-8.
Mancinelli R, Onori P, Gaudio E, DeMorrow S, Franchitto A, Francis H, Glaser S, Carpino G, Venter J, Alvaro D, Kopriva S, White M, Kossie A, Savage J, Alpini G. Follicle-stimulating hormone increases cholangiocyte proliferation by an autocrine mechanism via cAMP-dependent phosphorylation of ERK1/2 and Elk-1. Am J Physiol Gastrointest Liver Physiol 2009 Jul;297(1):G11-26.
Spies CM, Schaumann DH, Berki T, Mayer K, Jakstadt M, Huscher D, Wunder C, Burmester GR, Radbruch A, Lauster R, Scheffold A, Buttgereit F. Membrane glucocorticoid receptors are down regulated by glucocorticoids in patients with systemic lupus erythematosus and use a caveolin-1-independent expression pathway. Ann Rheum Dis 2006 Sep;65(9):1139-46.
Calder MD, Caveney AN, Smith LC, Watson AJ. Responsiveness of bovine cumulus-oocyte-complexes (COC) to porcine and recombinant human FSH, and the effect of COC quality on gonadotropin receptor and Cx43 marker gene mRNAs during maturation in vitro. Reprod Biol Endocrinol 2003 Feb 11;1:14.
Yi SE, LaPolt PS, Yoon BS, Chen JY, Lu JK, Lyons KM. The type I BMP receptor BmprIB is essential for female reproductive function. Proc Natl Acad Sci U S A 2001 Jul 3;98(14):7994-9.
Heckert LL. Activation of the rat follicle-stimulating hormone receptor promoter by steroidogenic factor 1 is blocked by protein kinase a and requires upstream stimulatory factor binding to a proximal E box element. Mol Endocrinol 2001 May;15(5):704-15.
Nomura T, Sasaki J, Mori H, Sato EF, Watanabe S, Kanda S, Matsuura J, Watanabe H, Inoue M. Expression of manganese superoxide dismutase mRNA in reproductive organs during the ovulatory process and the estrous cycle of the rat. Histochem Cell Biol 1996 Jan;105(1):1-6.