Ethanol potentiates follicle-stimulating hormone action in ovarian granulosa cells

in Journal of Endocrinology
Authors:
Yuta Kasahara Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan

Search for other papers by Yuta Kasahara in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-6369-1086
,
Hiroshi Kishi Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan

Search for other papers by Hiroshi Kishi in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0003-1562-410X
,
Ryo Yokomizo Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan

Search for other papers by Ryo Yokomizo in
Current site
Google Scholar
PubMed
Close
, and
Aikou Okamoto Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan

Search for other papers by Aikou Okamoto in
Current site
Google Scholar
PubMed
Close

Correspondence should be addressed to H Kishi: hrskishi@jikei.ac.jp
Restricted access
Rent on DeepDyve

Sign up for journal news

There are many previous reports on the effects of ethanol on physiological function, including reports of elevated blood estrogen levels in women who drank alcohol. However, the mechanism of ethanol's effects on ovarian functions, such as follicle development and hormone secretion, has not been fully clarified. Therefore, in this study, we investigated the impacts of ethanol on these phenomena and their mechanisms using a primary culture system of rat ovarian granulosa cells (GCs). In the present experiment, groups were created in which follicle-stimulating hormone (FSH) or ethanol was added alone or FSH and ethanol were co-added, and mRNA and protein expression in each group was measured for luteinizing hormone receptor (LHR) and sex steroid hormone synthase, as well as for estradiol (E2) production, cAMP production, and FSH receptor (FSHR) internalization rate. The addition of FSH induced mRNA expression of LHR and aromatase, which led to membrane LHR expression and E2 production. The coexistence of ethanol enhanced all these responses. The action of FSH is exerted via cAMP, and the co-addition of ethanol enhanced this cAMP production. Ethanol alone did not induce cAMP production. The enhancing effect of ethanol was also observed for cAMP induced by cholera toxin. Ethanol had no significant effect on the internalization rate of FSHR. In conclusion, ethanol increased FSH-stimulated cAMP production by increasing the activity of adenylyl cyclase, which enhanced FSH actions in rat GCs. Alcohol is an exacerbating factor in several female hormone-related diseases, and the mechanism of ethanol-induced increase in estrogen secretion revealed in this study may be involved in the pathogenesis of these diseases.

 

  • Collapse
  • Expand
  • Anwar MY, Marcus M & Taylor KC 2021 The association between alcohol intake and fecundability during menstrual cycle phases. Human Reproduction 36 25382548. (https://doi.org/10.1093/humrep/deab121)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ascoli M 1982 Internalization and degradation of receptor-bound human choriogonadotropin in Leydig tumor cells. Fate of the hormone subunits. Journal of Biological Chemistry 257 1330613311. (https://doi.org/10.1016/S0021-9258(1833447-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Blevins T, Mirshahi T, Chandler LJ & Woodward JJ 1997 Effects of acute and chronic ethanol exposure on heteromeric N-methyl-D-aspartate receptors expressed in HEK 293 cells. Journal of Neurochemistry 69 23452354. (https://doi.org/10.1046/j.1471-4159.1997.69062345.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chandler LJ, Newsom H, Sumners C & Crews F 1993 Chronic ethanol exposure potentiates NMDA excitotoxicity in cerebral cortical neurons. Journal of Neurochemistry 60 15781581. (https://doi.org/10.1111/j.1471-4159.1993.tb03326.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chiaffarino F, Cipriani S, Ricci E, La Vecchia C, Chiantera V, Bulfoni A & Parazzini F 2017 Alcohol consumption and risk of uterine myoma: a systematic review and meta analysis. PLoS One 12 e0188355. (https://doi.org/10.1371/journal.pone.0188355)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dattatreyamurty B, Figgs LW & Reichert LE 1987 Physical and functional association of follitropin receptors with cholera toxin-sensitive guanine nucleotide-binding protein. Journal of Biological Chemistry 262 1173711745. (https://doi.org/10.1016/S0021-9258(1860873-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dias JA, Cohen BD, Lindau-Shepard B, Nechamen CA, Peterson AJ & Schmidt A 2002 Molecular, structural, and cellular biology of follitropin and follitropin receptor. Vitamins and Hormones 64 249322. (https://doi.org/10.1016/s0083-6729(0264008-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Erickson GF, Wang C & Hsueh AJ 1979 FSH induction of functional LH receptors in granulosa cells cultured in a chemically defined medium. Nature 279 336338. (https://doi.org/10.1038/279336a0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Etique N, Chardard D, Chesnel A, Merlin JL, Flament S & & Grillier-Vuissoz I 2004 Ethanol stimulates proliferation, ERalpha and aromatase expression in MCF-7 human breast cancer cells. International Journal of Molecular Medicine 13 149155. (https://doi.org/10.3892/ijmm.13.1.149)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fan S, Meng Q, Gao B, Grossman J, Yadegari M, Goldberg ID & Rosen EM 2000 Alcohol stimulates estrogen receptor signaling in human breast cancer cell lines. Cancer Research 60 56355639.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fernandez DJ, Mcvicker BL, Tuma DJ & Tuma PL 2009 Ethanol selectively impairs clathrin-mediated internalization in polarized hepatic cells. Biochemical Pharmacology 78 648655. (https://doi.org/10.1016/j.bcp.2009.05.012)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fernandez SV 2011 Estrogen, alcohol consumption, and breast cancer. Alcoholism, Clinical and Experimental Research 35 389391. (https://doi.org/10.1111/j.1530-0277.2010.01355.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fernandez SV & Russo J 2010 Estrogen and xenoestrogens in breast cancer. Toxicologic Pathology 38 110122. (https://doi.org/10.1177/0192623309354108)

  • Finkelstein RA & Lospalluto JJ 1969 Pathogenesis of experimental cholera. Preparation and isolation of choleragen and choleragenoid. Journal of Experimental Medicine 130 185202. (https://doi.org/10.1084/jem.130.1.185)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fletcher PW & Reichert LE 1984 Cellular processing of follicle-stimulating hormone by Sertoli cells in serum-free culture. Molecular and Cellular Endocrinology 34 3949. (https://doi.org/10.1016/0303-7207(8490157-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fredriksson R, Lagerström MC, Lundin LG & Schiöth HB 2003 The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Molecular Pharmacology 63 12561272. (https://doi.org/10.1124/mol.63.6.1256)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gavaler JS & Van Thiel DH 1992 The association between moderate alcoholic beverage consumption and serum estradiol and testosterone levels in normal postmenopausal women: relationship to the literature. Alcoholism, Clinical and Experimental Research 16 8792. (https://doi.org/10.1111/j.1530-0277.1992.tb00642.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Goldenberg RL, Vaitukaitis JL & Ross GT 1972 Estrogen and follicle stimulation hormone interactions on follicle growth in rats. Endocrinology 90 14921498. (https://doi.org/10.1210/endo-90-6-1492)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gupta R, Qualls-Creekmore E & Yoshimura M 2013 Real-time monitoring of intracellular cAMP during acute ethanol exposure. Alcoholism, Clinical and Experimental Research 37 14561465. (https://doi.org/10.1111/acer.12133)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hankinson SE, Willett WC, Manson JE, Hunter DJ, Colditz GA, Stampfer MJ, Longcope C & Speizer FE 1995 Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women. Journal of the National Cancer Institute 87 12971302. (https://doi.org/10.1093/jnci/87.17.1297)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hirakawa T, Minegishi T, Abe K, Kishi H, Ibuki Y & Miyamoto K 1999 A role of insulin-like growth factor I in luteinizing hormone receptor expression in granulosa cells. Endocrinology 140 49654971. (https://doi.org/10.1210/endo.140.11.7112)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hsueh AJ, Adashi EY, Jones PB & Welsh TH 1984 Hormonal regulation of the differentiation of cultured ovarian granulosa cells. Endocrine Reviews 5 76127. (https://doi.org/10.1210/edrv-5-1-76)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Huang RD, Smith MF & Zahler WL 1982 Inhibition of forskolin-activated adenylate cyclase by ethanol and other solvents. Journal of Cyclic Nucleotide Research 8 385394.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hunzicker-Dunn M & Maizels ET 2006 FSH signaling pathways in immature granulosa cells that regulate target gene expression: branching out from protein kinase A. Cellular Signalling 18 13511359. (https://doi.org/10.1016/j.cellsig.2006.02.011)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Imai F, Kishi H, Nakao K, Nishimura T & Minegishi T 2014 IL-6 up-regulates the expression of rat LH receptors during granulosa cell differentiation. Endocrinology 155 14361444. (https://doi.org/10.1210/en.2013-1821)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Knecht M & Catt KJ 1982 Induction of luteinizing hormone receptors by adenosine 3',5'-monophosphate in cultured granulosa cells. Endocrinology 111 11921200. (https://doi.org/10.1210/endo-111-4-1192)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kumar S, Kralic JE, O'buckley TK, Grobin AC & Morrow AL 2003 Chronic ethanol consumption enhances internalization of alpha1 subunit-containing GABAA receptors in cerebral cortex. Journal of Neurochemistry 86 700708. (https://doi.org/10.1046/j.1471-4159.2003.01894.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Laurenza A, Sutkowski EM & Seamon KB 1989 Forskolin: a specific stimulator of adenylyl cyclase or a diterpene with multiple sites of action? Trends in Pharmacological Sciences 10 442447. (https://doi.org/10.1016/S0165-6147(8980008-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu Y, Zuo H, Wang Y, Tian L, Xu X, Xiong J & Pei X 2018 Ethanol promotes apoptosis in rat ovarian granulosa cells via the Bcl-2 family dependent intrinsic apoptotic pathway. Cellular and Molecular Biology 64 118125. (https://doi.org/10.14715/cmb/2018.64.1.21)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Luessen DJ, Sun H, Mcginnis MM, Hagstrom M, Marrs G, Mccool BA & Chen R 2019 Acute ethanol exposure reduces serotonin receptor 1A internalization by increasing ubiquitination and degradation of beta-arrestin2. Journal of Biological Chemistry 294 1406814080. (https://doi.org/10.1074/jbc.RA118.006583)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lyngsø J, Toft G, Høyer BB, Guldbrandsen K, Olsen J & Ramlau-Hansen CH 2014 Moderate alcohol intake and menstrual cycle characteristics. Human Reproduction 29 351358. (https://doi.org/10.1093/humrep/det417)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Marshall LM, Spiegelman D, Barbieri RL, Goldman MB, Manson JE, Colditz GA, Willett WC & Hunter DJ 1997 Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstetrics and Gynecology 90 967973. (https://doi.org/10.1016/s0029-7844(9700534-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Muti P, Trevisan M, Micheli A, Krogh V, Bolelli G, Sciajno R, Schünemann HJ & Berrino F 1998 Alcohol consumption and total estradiol in premenopausal women. Cancer Epidemiology, Biomarkers and Prevention 7 189193.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nagata C, Nakamura K, Oba S, Hayashi M, Takeda N & Yasuda K 2009 Association of intakes of fat, dietary fibre, soya isoflavones and alcohol with uterine fibroids in Japanese women. British Journal of Nutrition 101 14271431. (https://doi.org/10.1017/s0007114508083566)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nakao K, Kishi H, Imai F, Suwa H, Hirakawa T & Minegishi T 2015 TNF-α suppressed FSH-induced LH receptor expression through transcriptional regulation in rat granulosa cells. Endocrinology 156 31923202. (https://doi.org/10.1210/EN.2015-1238)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Parazzini F, Cipriani S, Bravi F, Pelucchi C, Chiaffarino F, Ricci E & Viganò P 2013 A metaanalysis on alcohol consumption and risk of endometriosis. American Journal of Obstetrics and Gynecology 209 106.e1106.10. (https://doi.org/10.1016/j.ajog.2013.05.039)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rabin RA & Molinoff PB 1983 Multiple sites of action of ethanol on adenylate cyclase. Journal of Pharmacology and Experimental Therapeutics 227 551556.

  • Reichman ME, Judd JT, Longcope C, Schatzkin A, Clevidence BA, Nair PP, Campbell WS & Taylor PR 1993 Effects of alcohol consumption on plasma and urinary hormone concentrations in premenopausal women. Journal of the National Cancer Institute 85 722727. (https://doi.org/10.1093/jnci/85.9.722)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rettori V, Skelley CW, Mccann SM & Dees WL 1987 Detrimental effects of short-term ethanol exposure on reproductive function in the female rat. Biology of Reproduction 37 10891096. (https://doi.org/10.1095/biolreprod37.5.1089)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rojas FJ & Asch RH 1985 Opposite effects of ethanol on the activation of adenylyl cyclase in human corpus luteum membranes. Molecular and Cellular Endocrinology 40 129136. (https://doi.org/10.1016/0303-7207(8590167-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sanders MM & Midgley AR 1982 Rat granulosa cell differentiation: an in vitro model. Endocrinology 111 614624. (https://doi.org/10.1210/endo-111-2-614)

  • Saxena S, Meehan D, Coney P & Wimalasena J 1990 Ethanol has direct inhibitory effects on steroidogenesis in human granulosa cells: specific inhibition of LH action. Alcoholism, Clinical and Experimental Research 14 522527. (https://doi.org/10.1111/j.1530-0277.1990.tb01192.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shield KD, Soerjomataram I & Rehm J 2016 Alcohol use and breast cancer: a critical review. Alcoholism, Clinical and Experimental Research 40 11661181. (https://doi.org/10.1111/acer.13071)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Simoni M, Gromoll J & Nieschlag E 1997 The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocrine Reviews 18 739773. (https://doi.org/10.1210/edrv.18.6.0320)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Suga S, Kato K, Ohgami T, Yamayoshi A, Adachi S, Asanoma K, Yamaguchi S, Arima T, Kinoshita K & Wake N 2007 An inhibitory effect on cell proliferation by blockage of the MAPK/estrogen receptor/MDM2 signal pathway in gynecologic cancer. Gynecologic Oncology 105 341350. (https://doi.org/10.1016/j.ygyno.2006.12.030)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Suzuki R, Iwasaki M, Inoue M, Sasazuki S, Sawada N, Yamaji T, Shimazu T, Tsugane S & Japan Public Health Center-Based Prospective Study Group 2010 Alcohol consumption-associated breast cancer incidence and potential effect modifiers: the Japan Public Health Center-based Prospective Study. International Journal of Cancer 127 685695. (https://doi.org/10.1002/ijc.25079)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ulloa-Aguirre A, Uribe A, Zariñán T, Bustos-Jaimes I, Pérez-Solis MA & Dias JA 2007 Role of the intracellular domains of the human FSH receptor in G(alphaS) protein coupling and receptor expression. Molecular and Cellular Endocrinology 260–262 153162. (https://doi.org/10.1016/j.mce.2005.11.050)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ulloa-Aguirre A & Zariñán T 2016 The follitropin receptor: matching structure and function. Molecular Pharmacology 90 596608. (https://doi.org/10.1124/mol.116.104398)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Van Thiel DH, Gavaler JS & Lester R 1978 Alcohol-induced ovarian failure in the rat. Journal of Clinical Investigation 61 624632. (https://doi.org/10.1172/JCI108973)

  • Vaughan M & Moss J 1978 Mechanism of action of choleragen. Journal of Supramolecular Structure 8 473488. (https://doi.org/10.1002/jss.400080410)

  • Wimalasena J, Meehan D, Dostal R & De Silva M 1993 Selective inhibition of luteinizing hormone action by ethanol in cultured human granulosa cells. Alcoholism, Clinical and Experimental Research 17 340344. (https://doi.org/10.1111/j.1530-0277.1993.tb00772.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wise LA, Palmer JR, Harlow BL, Spiegelman D, Stewart EA, Adams-Campbell LL & Rosenberg L 2004 Risk of uterine leiomyomata in relation to tobacco, alcohol and caffeine consumption in the Black Women's Health Study. Human Reproduction 19 17461754. (https://doi.org/10.1093/humrep/deh309)

    • PubMed
    • Search Google Scholar
    • Export Citation