Mechanisms of Luteinising Hormone Regulation in Female Steroidogenesis

David Cadagan^1, and Christopher Towlson²

¹Sciences Department, Staffordshire University, UK

²School of Biosciences, Nottingham University, UK

Cite this paper

David Cadagan and Christopher Towlson. Mechanisms of Luteinising Hormone Regulation in Female Steroidogenesis. American Journal of Medical Case Reports. 2017; 5(3):65-68. doi: 10.12691/AJMCR-5-3-6

Abstract

Understanding the mechanisms of steroidogenic regulation in female fertility is fundamental to determining dysfunction. Research has revealed a strong relationship between fertility and metabolic disturbances. With many endocrine signals involved in activation of steroidogenic cascades, it has become necessary to map the complex cross-talk between these regulatory systems and this review looks to establish this based on current understanding. Luteininsing hormone is a vital endocrine hormone that is already known to signal via these pathways, although its involvement in metabolic disturbance is less understood. Studies investigating activation of the LH receptor in key steroidogenic cells, ovarian theca and granulosa, have highlighted overlaps in important signaling cascades including PKC/MAPK/PKA and PI3K. Here, we review LH and its signaling cross-talk in key steroidogenic pathways.

Keywords

luteinising hormone (LH), lutropin, Steroidogenesis, gonadotropin, ovulation, LH Receptor, Cyclic adenomonophosphate (cAMP), Diacylglycerol (DAG), protein kinase C Pathway, MAPK pathway

Copyright

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References

[1]	Distiller LA, Sagel J, Morley JE, Joffe BI, Seftel HC: Pituitary Responsiveness to Luteinizing Hormone-Releasing Hormone in Insulin-Dependent Diabetes-Mellitus. Diabetes 1975, 24(4): 378-380.
[2]	Doi SAR, Towers PA, Scott CJ, Al-Shoumer KAS: PCOS: an ovarian disorder that leads to dysregulation in the hypothalamic-pituitary-adrenal axis? Eur J Obstet Gyn R B 2005, 118(1): 4-16.
[3]	Ascoli M, Fanelli F, Segaloff DL: The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocr Rev 2002, 23(2):141-174.
[4]	Ascoli M: Molecular basis of the regulation of the lutropin/choriogonadotropin receptor. Biochem Soc T 1997, 25(3):1021-1026.
[5]	Mestman JH, Schmidtsarosi C: Diabetes-Mellitus and Fertility-Control - Contraception Management Issues. American Journal of Obstetrics and Gynecology 1993, 168(6): 2012-2020.
[6]	Schroeder F, Frolov A, Schoer J, Gallegos A, Atshaves B, Stolowich N, Scott A, Kier A: Intracellular Cholesterol Trafficking. 1998: 213-234.
[7]	Hirshfield AN: Development of follicles in the mammalian ovary. Int Rev Cytol 1991, 124: 43-101.
[8]	Dufau ML, Morris CHT, Hu ZZ, Geng Y, Xie X, Zhuang L, Zhang R, Buczko E: The Luteinizing-Hormone Receptor. Front Endocrinol 1994, 5: 51-60.
[9]	Schroeder F, Frolov A, Schoer JK, Gallegos AM, Atshaves BP, Stolowich NJ, Scott AI, Kier AB: Intracellular sterol binding proteins: Cholesterol transport and membrane domains. Intracellular Cholesterol Trafficking 1998:213-234.
[10]	Gilchrist RL, Ryu KS, Ji I, Ji TH: The luteinizing hormone/chorionic gonadotropin receptor has distinct transmembrane conductors for cAMP and inositol phosphate signals. J Biol Chem 1996, 271(32):19283-19287.
[11]	Hsueh AJW, Adashi EY, Jones PBC, Welsh TH: Hormonal-Regulation of the Differentiation of Cultured Ovarian Granulosa-Cells. Endocrine Reviews 1984, 5(1):76-127.
[12]	Richards JS: Maturation of Ovarian Follicles - Actions and Interactions of Pituitary and Ovarian Hormones on Follicular Cell-Differentiation. Physiological Reviews 1980, 60(1):51-89.
[13]	Kreusser W, Mader H, Haag WD, Ritz E: Diminished Response of Ovarian Camp to Luteinizing-Hormone in Experimental Uremia. Kidney International 1982, 22(3): 272-279.
[14]	Ginsburg ES, Owen WF: Reproductive Endocrinology and Pregnancy in Women on Hemodialysis. Semin Dialysis 1993, 6(2): 105-116.
[15]	Richards JS: Maturation of ovarian follicles: actions and interactions of pituitary and ovarian hormones on follicular cell differentiation. Physiol Rev 1980, 60(1):51-89.
[16]	Salvador LM, Maizels E, Hales DB, Miyamoto E, Yamamoto H, Hunzicker-Dunn M: Acute signaling by the LH receptor is independent of protein kinase C activation. Endocrinology 2002, 143(8): 2986-2994.
[17]	Newton AC: Regulation of protein kinase C. Curr Opin Cell Biol 1997, 9(2):161-167.
[18]	Zhu X, Gilbert S, Birnbaumer M, Birnbaumer L: Dual signaling potential is common among Gs-coupled receptors and dependent on receptor density. Mol Pharmacol 1994, 46(3): 460-469.
[19]	Iyengar R, Birnbaumer L: Roles of G proteins and G protein subunits in signal transduction. Lymphokine Res 1990, 9(4): 533-537.
[20]	Salvador LM, Maizels E, Hales DB, Miyamoto E, Yamamoto H, Hunzicker-Dunn M: Acute signaling by the LH receptor is independent of protein kinase C activation. Endocrinology 2002, 143(8): 2986-2994.
[21]	Geffner M, Kaplan S, Bersch N, Golde D, Landaw E, Chang R: Persistence of insulin resistance in polycystic ovarian disease after inhibition of ovarian steroid secretion. Fertil Steril 1986, 45: 327-333.
[22]	Camps M, Nichols A, Arkinstall S: Dual specificity phosphatases: a gene family for control of MAP kinase function. FASEB J 2000, 14(1):6-16.
[23]	Keyse SM: Protein phosphatases and the regulation of mitogen-activated protein kinase signalling. Curr Opin Cell Biol 2000, 12(2):186-192.
[24]	Alberts B: The Molecular Biology of the Cell. Garland Science, NewYork 2002.
[25]	Nelson-Degrave VL, Wickenheisser JK, Hendricks KL, Asano T, Fujishiro M, Legro RS, Kimball SR, Strauss JF, 3rd, McAllister JM: Alterations in mitogen-activated protein kinase kinase and extracellular regulated kinase signaling in theca cells contribute to excessive androgen production in polycystic ovary syndrome. Mol Endocrinol 2005, 19(2):379-390.
[26]	Fukuda S, Orisaka M, Tajima K, Hattori K, Kotsuji F: Luteinizing hormone-induced Akt phosphorylation and androgen production are modulated by MAP Kinase in bovine theca cells. J Ovarian Res 2009, 2(1):17.
[27]	Cadagan D, Khan R, Amer S: Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome. Reprod Biol 2016, 16(1):53-60.
[28]	Fukuda S, Orisaka M, Tajima K, Kotsuji F: Luteinizing Hormone Stimulates CYP17A1 mRNA Expression and Androgen Production in Bovine Theca Cells via Activation of the PI3K/Akt Pathway. Biology of Reproduction 2009, 81(525).
[29]	Marino M, Acconcia F, Trentalance A: Biphasic estradiol-induced AKT phosphorylation is modulated by PTEN via MAP kinase in HepG2 cells. Mol Biol Cell 2003, 14(6): 2583-2591.
[30]	Tajima K, Yoshii K, Fukuda S, Orisaka M, Miyamoto K, Amsterdam A, Kotsuji F: Luteinizing hormone-induced extracellular-signal regulated kinase activation differently modulates progesterone and androstenedione production in bovine theca cells. Endocrinology 2005, 146(7):2903-2910.
[31]	de Rooij J, Zwartkruis FJ, Verheijen MH, Cool RH, Nijman SM, Wittinghofer A, Bos JL: Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 1998, 396(6710):474-477.
[32]	Seger R, Hanoch T, Rosenberg R, Dantes A, Merz WE, Strauss JF, 3rd, Amsterdam A: The ERK signaling cascade inhibits gonadotropin-stimulated steroidogenesis. J Biol Chem 2001, 276(17): 13957-13964.