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Hormonal Regulation of GnRH and LHβ mRNA Expression in Cultured Rat Granulosa Cells

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Abstract

We have recently demonstrated that the rat ovary expresses LHβ, FSHβ, and the common alpha subunit mRNA. In the present report, we studied the regulation of LHβ and of gonadotropin-releasing hormone (GnRH) mRNA expression in granulosa cells that were isolated from immature rats treated with either estrogen or pregnant mare serum gonadotropin (PMSG). In both cell types, GnRH agonist treatment resulted in a decrease in LHβ mRNA expression. However, only in cells derived from PMSG-treated rats, GnRH treatment produced an increase in GnRH mRNA expression. A markedly increased GnRH mRNA expression was also obtained in granulosa cells derived from PMSG-primed rats in response to LH. In addition, FSH reduced the expression of LHβ mRNA in granulosa cells from estrogen-primed rats. These results suggest that the expression of LHβ in the ovary is regulated by locally produced GnRH and by FSH from either the ovary or the pituitary.

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References

  • Amsterdam, A., Dantes, A., & Liscovitch, M. (1994). Role of phospholipase-D and phosphatidic acid in mediating gonadotropin-releasing hormone-induced inhibition of preantral granulosa cell differentiation. Endocrinology, 135(3), 1205–1211.

    Article  PubMed  CAS  Google Scholar 

  • Andrews, W. V., Maurer, R. A., & Conn, P. M. (1988). Stimulation of rat luteinizing hormone-beta messenger RNA levels by gonadotropin releasing hormone. Apparent role for protein kinase C. Journal of Biological Chemistry, 263(27), 13755–13761.

    PubMed  CAS  Google Scholar 

  • Bahk, J. Y., Hyun, J. S., Chung, S. H., Lee, H., Kim, M. O., Lee, B. H., et al. (1995). Stage specific identification of the expression of GnRH mRNA and localization of the GnRH receptor in mature rat and adult human testis. Journal of Urology, 154(5), 1958–1961.

    Article  PubMed  CAS  Google Scholar 

  • Baram, T., & Koch, Y. (1977). Evidence for the dependence of serum luteinizing hormone surge on a transient, enhanced secretion of gonadotropin-releasing hormone from the hypothalamus. Neuroendocrinology, 23(3), 151–156.

    Article  PubMed  CAS  Google Scholar 

  • Bauer, T. W., Moriarty, C. M., & Childs, G. V. (1981). Studies of immunoreactive gonadotropin releasing hormone (GnRH) in the rat anterior pituitary. Journal of Histochemistry and Cytochemistry, 29(10), 1171–1178.

    PubMed  CAS  Google Scholar 

  • Bex, F. J., & Corbin, A. (1984). Cyclic response of hypophysectomized rats to ovulation induced by LHRH agonist: mediation by prostaglandins. Life Sciences, 35(9), 969–979.

    Article  PubMed  CAS  Google Scholar 

  • Billig, H., Furuta, I., & Hsueh, A. J. (1994). Gonadotropin-releasing hormone directly induces apoptotic cell death in the rat ovary: biochemical and in situ detection of deoxyribonucleic acid fragmentation in granulosa cells. Endocrinology, 134(1), 245–252.

    Article  PubMed  CAS  Google Scholar 

  • Clayton, R. N., Katikineni, M., Chan, V., Dufau, M. L., & Catt, K. J. (1980). Direct inhibition of testicular function by gonadotropin-releasing hormone: mediation by specific gonadotropin-releasing hormone receptors in interstitial cells. Proceedings of the National Academy of Sciences of the United States of America, 77(8), 4459–4463.

    Article  PubMed  CAS  Google Scholar 

  • Clayton, R. N., Eccleston, L., Gossard, F., Thalbard, J. C., & Morel, G. (1992). Rat granulosa cells express the gonadotrophin-releasing hormone gene: evidence from in-situ hybridization histochemistry. Journal of Molecular Endocrinology, 9(3), 189–195.

    Article  PubMed  CAS  Google Scholar 

  • Corbin, A., & Bex, F. J. (1981). Luteinizing hormone releasing hormone agonists induce ovulation in hypophysectomized proestrous rats: direct ovarian effect. Life Sciences, 29(2), 185–192.

    Article  PubMed  CAS  Google Scholar 

  • Dekel, N., Sherizly, I., Tsafriri, A., & Naor, Z. (1983). A comparative study of the mechanism of action of luteinizing hormone and a gonadotropin releasing hormone analog on the ovary. Biology of Reproduction, 28(1), 161–166.

    Article  PubMed  CAS  Google Scholar 

  • Ekholm, C., Hillensjo, T., & Isaksson, O. (1981). Gonadotropin releasing hormone agonists stimulate oocyte meiosis and ovulation in hypophysectomized rats. Endocrinology, 108(5), 2022–2024.

    Article  PubMed  CAS  Google Scholar 

  • Funkenstein, B., Nimrod, A., & Lindner, H. R. (1980). The development of steroidogenic capability and responsiveness to gonadotropins in cultured neonatal rat ovaries. Endocrinology, 106(1), 98–106.

    Article  PubMed  CAS  Google Scholar 

  • Granot, I., & Dekel, N. (1994). Phosphorylation and expression of connexin-43 ovarian gap junction protein are regulated by luteinizing hormone. Journal of Biological Chemistry, 269(48), 30502–30509.

    PubMed  CAS  Google Scholar 

  • Hillensjo, T., & LeMaire, W. J. (1980). Gonadotropin releasing hormone agonists stimulate meiotic maturation of follicle-enclosed rat oocytes in vitro. Nature, 287(5778), 145–146.

    Article  PubMed  CAS  Google Scholar 

  • Hovatta, O., Huhtaniemi, I., & Wahlstrom, T. (1986). Testicular gonadotrophins and their receptors in human cryptorchidism as revealed by immunohistochemistry and radioreceptor assay. Acta Endocrinologica (Copenhagen), 111(1), 128–132.

    CAS  Google Scholar 

  • Hsueh, A. J., & Erickson, G. F. (1979). Extrapituitary action of gonadotropin-releasing hormone: direct inhibition ovarian steroidogenesis. Science, 204(4395), 854–855.

    Article  PubMed  CAS  Google Scholar 

  • Jones, P. B., & Hsueh, A. J. (1980). Direct inhibitory effect of gonadotropin-releasing hormone upon luteal luteinizing hormone receptor and steroidogenesis in hypophysectomized rats. Endocrinology, 107(6), 1930–1936.

    Article  PubMed  CAS  Google Scholar 

  • Jones, P. B., Conn, P. M., Marian, J., & Hsueh, A. J. (1980). Binding of gonadotropin releasing hormone agonist to rat ovarian granulosa cells. Life Sciences, 27(22), 2125–2132.

    Article  PubMed  CAS  Google Scholar 

  • Kang, S. K., Tai, C. J., Nathwani, P. S., & Leung, P. C. (2001). Differential regulation of two forms of gonadotropin-releasing hormone messenger ribonucleic acid in human granulosa-luteal cells. Endocrinology, 142(1), 182–192.

    Article  PubMed  CAS  Google Scholar 

  • Koch, Y., Baram, T., Chobsieng, P., & Fridkin, M. (1974). Enzymic degradation of luteinizing hormone-releasing hormone (LH-RH) by hypothalamic tissue. Biochemical and Biophysical Research Communications, 61(1), 95–103.

    Article  PubMed  CAS  Google Scholar 

  • Kumar, T. R. (2007). Functional analysis of LHbeta knockout mice. Molecular and Cellular Endocrinology, 269(1–2), 81–84.

    Article  PubMed  CAS  Google Scholar 

  • Lalloz, M. R., Detta, A., & Clayton, R. N. (1988). Gonadotropin-releasing hormone is required for enhanced luteinizing hormone subunit gene expression in vivo. Endocrinology, 122(4), 1681–1688.

    Article  PubMed  CAS  Google Scholar 

  • Leung, P. C., Cheng, C. K., & Zhu, X. M. (2003). Multi-factorial role of GnRH-I and GnRH-II in the human ovary. Molecular and Cellular Endocrinology, 202(1–2), 145–153.

    PubMed  CAS  Google Scholar 

  • Liscovitch, M., & Amsterdam, A. (1989). Gonadotropin-releasing hormone activates phospholipase D in ovarian granulosa cells. Possible role in signal transduction. Journal of Biological Chemistry, 264(20), 11762–11767.

    PubMed  CAS  Google Scholar 

  • Ma, X., Dong, Y., Matzuk, M. M., & Kumar, T. R. (2004). Targeted disruption of luteinizing hormone beta-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility. Proceedings of the National Academy of Sciences of the United States of America, 101(49), 17294–17299.

    Article  PubMed  CAS  Google Scholar 

  • McGee, E. A., Perlas, E., LaPolt, P. S., Tsafriri, A., & Hsueh, A. J. (1997). Follicle-stimulating hormone enhances the development of preantral follicles in juvenile rats. Biology of Reproduction, 57(5), 990–998.

    Article  PubMed  CAS  Google Scholar 

  • Naor, Z., Zilberstein, M., Zakut, H., Lindner, H. R., & Dekel, N. (1983). Dissociation between the direct stimulatory and inhibitory effects of a gonadotropin-releasing hormone analog on ovarian functions. Molecular and Cellular Endocrinology, 31(2–3), 261–270.

    Article  PubMed  CAS  Google Scholar 

  • Naor, Z., Zilberstein, M., Zakut, H., & Dekel, N. (1984). Gonadotropin releasing hormone: regulation of phospholipid turnover and prostaglandin production in ovarian granulosa cells. Life Sciences, 35(4), 389–398.

    Article  PubMed  CAS  Google Scholar 

  • Neal, P., & Baker, T. G. (1974). Response of mouse ovaries in vivo and in organ culture to pregnant mare’s serum gonadotrophin and human chorionic gonadotrophin. Journal of Reproduction and Fertility, 37(2), 399–404.

    Article  PubMed  CAS  Google Scholar 

  • Oikawa, M., Dargan, C., Ny, T., & Hsueh, A. J. (1990). Expression of gonadotropin-releasing hormone and prothymosin-alpha messenger ribonucleic acid in the ovary. Endocrinology, 127(5), 2350–2356.

    Article  PubMed  CAS  Google Scholar 

  • Orly, J., Sato, G., & Erickson, G. F. (1980). Serum suppresses the expression of hormonally induced functions in cultured granulosa cells. Cell, 20(3), 817–827.

    Article  PubMed  CAS  Google Scholar 

  • Park, J. Y., Park, J. H., Park, H. J., Lee, J. Y., Lee, Y. I., Lee, K., et al. (2001). Stage-dependent regulation of ovarian pituitary adenylate cyclase-activating polypeptide mRNA levels by GnRH in cultured rat granulosa cells. Endocrinology, 142(9), 3828–3835.

    Article  PubMed  CAS  Google Scholar 

  • Pawson, A. J., Morgan, K., Maudsley, S. R., & Millar, R. P. (2003). Type II gonadotrophin-releasing hormone (GnRH-II) in reproductive biology. Reproduction, 126(3), 271–278.

    Article  PubMed  CAS  Google Scholar 

  • Pieper, D. R., Richards, J. S., & Marshall, J. C. (1981). Ovarian gonadotropin-releasing hormone (GnRH) receptors: characterization, distribution, and induction by GnRH. Endocrinology, 108(4), 1148–1155.

    Article  PubMed  CAS  Google Scholar 

  • Reeves, J. J., Seguin, C., Lefebvre, F. A., Kelly, P. A., & Labrie, F. (1980). Similar luteinizing hormone-releasing hormone binding sites in rat anterior pituitary and ovary. Proceedings of the National Academy of Sciences of the United States of America, 77(9), 5567–5571.

    Article  PubMed  CAS  Google Scholar 

  • Schirman-Hildesheim, T. D., Bar, T., Ben-Aroya, N., & Koch, Y. (2005). Differential gonadotropin-releasing hormone (GnRH) and GnRH receptor messenger ribonucleic acid expression patterns in different tissues of the female rat across the estrous cycle. Endocrinology, 146(8), 3401–3408.

    Article  PubMed  CAS  Google Scholar 

  • Schirman-Hildesheim, T. D., Gershon, E., Litichever, N., Galiani, D., Ben-Aroya, N., Dekel, N., et al. (2008). Local production of the gonadotropic hormones in the rat ovary. Molecular and Cellular Endocrinology, 282(1–2), 32–38.

    Article  PubMed  CAS  Google Scholar 

  • Sharma, S. C., & Richards, J. S. (2000). Regulation of AP1 (Jun/Fos) factor expression and activation in ovarian granulosa cells. Relation of JunD and Fra2 to terminal differentiation. Journal of Biological Chemistry, 275(43), 33718–33728.

    Article  PubMed  CAS  Google Scholar 

  • Siebers, J. W., Peters, F., Zenzes, M. T., Schmidtke, J., & Engel, W. (1977). Binding of human chorionic gonadotrophin to rat ovary during development. Journal of Endocrinology, 73(3), 491–496.

    Article  PubMed  CAS  Google Scholar 

  • Sokka, T. A., Hamalainen, T. M., & Huhtaniemi, I. T. (1992). Ontogeny of gonadotropin action in the rat ovary. Journal of Physiology and Pharmacology, 43(4 Suppl 1), 21–32.

    PubMed  Google Scholar 

  • Swerdloff, R. S., Bhasin, S., & Sokol, R. Z. (1984). GnRH-like factors in the rat testis and human seminal plasma. Annals of the New York Academy of Sciences, 438, 382–389.

    Article  PubMed  CAS  Google Scholar 

  • Vidyashankar, N., & Moudgal, N. R. (1984). Effect of pregnant mare serum gonadotropin on the induction and degradation of FSH and LH receptors in the granulosa cell of the immature rat. Molecular and Cellular Endocrinology, 37(2), 215–222.

    Article  PubMed  CAS  Google Scholar 

  • Wahlstrom, T., Huhtaniemi, I., Hovatta, O., & Seppala, M. (1983). Localization of luteinizing hormone, follicle-stimulating hormone, prolactin, and their receptors in human and rat testis using immunohistochemistry and radioreceptor assay. Journal of Clinical Endocrinology and Metabolism, 57(4), 825–830.

    Article  PubMed  CAS  Google Scholar 

  • Whitelaw, P. F., Eidne, K. A., Sellar, R., Smyth, C. D., & Hillier, S. G. (1995). Gonadotropin-releasing hormone receptor messenger ribonucleic acid expression in rat ovary. Endocrinology, 136(1), 172–179.

    Article  PubMed  CAS  Google Scholar 

  • Wong, T. T., & Zohar, Y. (2004). Novel expression of gonadotropin subunit genes in oocytes of the gilthead seabream (Sparus aurata). Endocrinology, 145(11), 5210–5220.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, F. P., Markkula, M., Toppari, J., & Huhtaniemi, I. (1995a). Novel expression of luteinizing hormone subunit genes in the rat testis. Endocrinology, 136(7), 2904–2912.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, F. P., Rannikko, A., & Huhtaniemi, I. (1995b). Isolation and characterization of testis-specific cDNAs for luteinizing hormone beta-subunit in the rat. Biochemical and Biophysical Research Communications, 210(3), 858–865.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Ms. Nurit Ben-Aroya and Mrs. Dalia Galiani for their help. N. Dekel is the incumbent of the Philip M. Klutznick Professorial Chair in Developmental Biology.

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Authors and Affiliations

  1. Department of Neurobiology, Weizmann Institute of Science, Rehovot, 76100, Israel

    Naomi Litichever, Eran Gershon & Yitzhak Koch

  2. Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

    Nava Dekel

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  1. Naomi Litichever
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  2. Eran Gershon
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  3. Nava Dekel
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  4. Yitzhak Koch
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Correspondence to Yitzhak Koch.

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Litichever, N., Gershon, E., Dekel, N. et al. Hormonal Regulation of GnRH and LHβ mRNA Expression in Cultured Rat Granulosa Cells. J Mol Neurosci 39, 78–85 (2009). https://doi.org/10.1007/s12031-009-9185-8

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  • DOI: https://doi.org/10.1007/s12031-009-9185-8

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