{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:33:55Z","timestamp":1776353635114,"version":"3.51.2"},"reference-count":59,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Aromatase is an enzyme catalyzing the final step of 17\u03b2-estradiol (E2) biosynthesis. Aromatase-deficient (ArKO) mice displayed vital roles of E2 at various tissue sites, including ovary. Here, we report attenuated responses of ArKO ovary to equine chorionic gonadotropin (eCG), an alternative to FSH. Ovarian contents of cAMP and anti-M\u00fcllerian hormone (AMH), putative factors reducing sensitivity to gonadotropins, were significantly elevated in ArKO mice compared with those in wild type (WT) mice in the basal state. Accordingly, eCG-induced ovarian alterations in cAMP contents, phosphorylation levels of signaling molecules, and mRNA expression of eCG-targeted genes were blunted in ArKO mice compared with those in WT mice. Treatment of ArKO mice with E2 decreased ovarian cAMP and AMH contents to the WT levels but did not restore the sensitivity. Microarray analysis coupled with quantitative RT-PCR analysis identified 7 genes of which the mRNA expression levels in ArKO ovaries were significantly different from those in the WT ovaries in the basal state and were not normalized by E2 supplementation, indicating possible involvement of these gene products in the determination of ovarian sensitivity to eCG. Thus, present analyses revealed that estrogen deficiency attenuates sensitivity of the ovary to gonadotropin, which might be associated with alterations in the ovarian contents of multiple molecules including cAMP and AMH. Given the importance of the ovarian responses to gonadotropins in reproductive function, detailed knowledge about the underlying mechanisms of abnormalities in the ArKO ovary might help to develop potential targets for infertility treatments.<\/jats:p>","DOI":"10.1210\/en.2015-1701","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T18:00:38Z","timestamp":1456509638000},"page":"2093-2103","source":"Crossref","is-referenced-by-count":3,"title":["Characterization of Ovarian Responses to Equine Chorionic Gonadotropin of Aromatase-Deficient Mice With or Without 17\u03b2-Estradiol Supplementation"],"prefix":"10.1210","volume":"157","author":[{"given":"Katsumi","family":"Toda","sequence":"first","affiliation":[{"name":"Departments of Biochemistry (K.T.), Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Hayashi","sequence":"first","affiliation":[{"name":"Pathology (Y.H.), Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Ono","sequence":"first","affiliation":[{"name":"Gastroenterology and Hepatology (M.O., T.S.), Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiji","family":"Saibara","sequence":"first","affiliation":[{"name":"Gastroenterology and Hepatology (M.O., T.S.), Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2016,2,26]]},"reference":[{"key":"2020071612135162200_B1","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1210\/er.2009-0012","article-title":"The mammalian ovary from genesis to revelation","volume":"30","author":"Edson","year":"2009","journal-title":"Endocr Rev"},{"key":"2020071612135162200_B2","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S0039-128X(00)00114-8","article-title":"Ovulation: a multi-gene, multi-step process","volume":"65","author":"Robker","year":"2000","journal-title":"Steroids"},{"key":"2020071612135162200_B3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-642-02062-9_1","article-title":"New insights into ovarian function","volume":"198","author":"Richards","year":"2010","journal-title":"Handb Exp Pharmacol"},{"key":"2020071612135162200_B4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0303-7207(01)00469-5","article-title":"Gonadotropic control of ovarian follicular growth and development","volume":"179","author":"Hillier","year":"2001","journal-title":"Mol Cell Endocrinol"},{"key":"2020071612135162200_B5","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1210\/endo.137.3.8603610","article-title":"A stimulatory role of cyclic adenosine 3\u2032,5\u2032-monophosphate in follicle-stimulating hormone-activated mitogen-activated protein kinase signaling pathway in rat ovarian granulosa cells","volume":"137","author":"Das","year":"1996","journal-title":"Endocrinology"},{"key":"2020071612135162200_B6","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1210\/mend.14.8.0500","article-title":"Follicle-stimulating hormone (FSH) stimulates phosphorylation and activation of protein kinase B (PKB\/Akt) and serum and glucocorticoid-induced kinase (Sgk): evidence for A kinase-independent signaling by FSH in granulosa cells","volume":"14","author":"Gonzalez-Robayna","year":"2000","journal-title":"Mol Endocrinol"},{"key":"2020071612135162200_B7","doi-asserted-by":"crossref","first-page":"7167","DOI":"10.1074\/jbc.M203901200","article-title":"Follicle-stimulating hormone activates extracellular signal-regulated kinase but not extracellular signal-regulated kinase kinase through a 100-kDa phosphotyrosine phosphatase","volume":"278","author":"Cottom","year":"2003","journal-title":"J Biol Chem"},{"key":"2020071612135162200_B8","doi-asserted-by":"crossref","first-page":"3985","DOI":"10.1210\/en.2003-0293","article-title":"Protein kinase B is obligatory for follicle-stimulating hormone-induced granulosa cell differentiation","volume":"144","author":"Zeleznik","year":"2003","journal-title":"Endocrinology"},{"key":"2020071612135162200_B9","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1210\/me.2006-0446","article-title":"Follicle-stimulating hormone-induced activation of Gata 4 contributes in the up-regulation of Cyp19 expression in rat granulosa cells","volume":"21","author":"Kwintkiewicz","year":"2007","journal-title":"Mol Endocrinol"},{"key":"2020071612135162200_B10","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1677\/ERC-07-0238","article-title":"Gonadotropin-stimulated epidermal growth factor receptor expression in human ovarian surface epithelial cells: involvement of cyclic AMP-dependent exchange protein activated by cAMP pathway","volume":"16","author":"Choi","year":"2009","journal-title":"Endocr Relat Cancer"},{"key":"2020071612135162200_B11","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1210\/me.2012-1307","article-title":"IGF-I Signaling is essential for FSH stimulation of AKT and steroidogenic genes in granulosa cells","volume":"27","author":"Zhou","year":"2013","journal-title":"Mol Endocrinol"},{"key":"2020071612135162200_B12","doi-asserted-by":"crossref","first-page":"16778","DOI":"10.1073\/pnas.1414648111","article-title":"Follicle-stimulating hormone regulates expression and activity of epidermal growth factor receptor in the murine ovarian follicle","volume":"111","author":"El-Hayek","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612135162200_B13","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1210\/me.2007-0020","article-title":"Follicle-stimulating hormone induces multiple signaling cascades: evidence that activation of Rous sarcoma oncogene, RAS, and the epidermal growth factor receptor are critical for granulosa cell differentiation","volume":"21","author":"Wayne","year":"2007","journal-title":"Mol Endocrinol"},{"key":"2020071612135162200_B14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fendo.2011.00045","article-title":"2011 Mapping the follicle-stimulating hormone-induced signaling networks","volume":"2","author":"Gloaguen","year":"2011","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2020071612135162200_B15","doi-asserted-by":"crossref","first-page":"19431","DOI":"10.1074\/jbc.M401235200","article-title":"Follicle-stimulating hormone activation of hypoxia-inducible factor-1 by the phosphatidylinositol 3-kinase\/AKT\/Ras homolog enriched in brain (Rheb)\/mammalian target of rapamycin (mTOR) pathway is necessary for induction of select protein markers of follicular differentiation","volume":"279","author":"Alam","year":"2004","journal-title":"J Biol Chem"},{"key":"2020071612135162200_B16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1146\/annurev.physiol.64.081601.142703","article-title":"Aromatase\u2013a brief overview","volume":"64","author":"Simpson","year":"2002","journal-title":"Annu Rev Physiol"},{"key":"2020071612135162200_B17","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1210\/er.2010-0013","article-title":"The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders","volume":"32","author":"Miller","year":"2011","journal-title":"Endocr Rev"},{"key":"2020071612135162200_B18","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1530\/rep.0.1220215","article-title":"Intraovarian actions of oestrogen","volume":"122","author":"Rosenfeld","year":"2001","journal-title":"Reproduction"},{"key":"2020071612135162200_B19","doi-asserted-by":"crossref","first-page":"6965","DOI":"10.1073\/pnas.95.12.6965","article-title":"Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene","volume":"95","author":"Fisher","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612135162200_B20","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1677\/joe.0.1700099","article-title":"Targeted disruption of the aromatase P450 gene (Cyp19) in mice and their ovarian and uterine responses to 17\u03b2-oestradiol","volume":"170","author":"Toda","year":"2001","journal-title":"J Endocrinol"},{"key":"2020071612135162200_B21","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1210\/endo.141.7.7578","article-title":"An age-related ovarian phenotype in mice with targeted disruption of the Cyp 19 (aromatase) gene","volume":"141","author":"Britt","year":"2000","journal-title":"Endocrinology"},{"key":"2020071612135162200_B22","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1210\/en.2011-1462","article-title":"Impact of ovarian sex steroids and ovulatory gene expression in aromatase-null mice","volume":"153","author":"Toda","year":"2012","journal-title":"Endocrinology"},{"key":"2020071612135162200_B23","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s11248-013-9771-y","article-title":"Aromatase-null mice expressing enhanced green fluorescent protein in germ cells provide a model system to assess estrogen-dependent ovulatory responses","volume":"23","author":"Toda","year":"2014","journal-title":"Transgenic Res"},{"key":"2020071612135162200_B24","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1093\/humupd\/dmg007","article-title":"Clinical management of low ovarian response to stimulation for IVF: a systematic review","volume":"9","author":"Tarlatzis","year":"2003","journal-title":"Hum Reprod Update"},{"key":"2020071612135162200_B25","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1677\/JOE-08-0257","article-title":"Preserved tissue structure of efferent ductules in aromatase-deficient mice","volume":"199","author":"Toda","year":"2008","journal-title":"J Endocrinol"},{"key":"2020071612135162200_B26","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.mce.2015.04.027","article-title":"Co-administration of insulin with a gonadotropin partly improves ovulatory responses of estrogen-deficient mice","volume":"411","author":"Toda","year":"2015","journal-title":"Mol Cell Endocrinol"},{"key":"2020071612135162200_B27","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1006\/dbio.1996.0226","article-title":"Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors","volume":"178","author":"Tsafriri","year":"1996","journal-title":"Dev Biol"},{"key":"2020071612135162200_B28","doi-asserted-by":"crossref","first-page":"4891","DOI":"10.1210\/endo.142.11.8486","article-title":"Anti-M\u00fcllerian hormone attenuates the effects of FSH on follicle development in the mouse ovary","volume":"142","author":"Durlinger","year":"2001","journal-title":"Endocrinology"},{"key":"2020071612135162200_B29","first-page":"4","article-title":"The cyclic AMP pathway","author":"Sassone-Corsi","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2020071612135162200_B30","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1210\/endo-97-4-898","article-title":"Changes with age in levels of serum gonadotropins, prolactin and gonadal steroids in prepubertal male and female rats","volume":"97","author":"D\u00f6hler","year":"1975","journal-title":"Endocrinology"},{"key":"2020071612135162200_B31","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1210\/endo-108-5-1658","article-title":"Pituitary and gonadal gonadotropin-releasing hormone receptors during sexual maturation in the rat","volume":"108","author":"Dalkin","year":"1981","journal-title":"Endocrinology"},{"key":"2020071612135162200_B32","doi-asserted-by":"crossref","first-page":"3950","DOI":"10.1210\/en.2003-1628","article-title":"The effects of estrogen on the expression of genes underlying the differentiation of somatic cells in the murine gonad","volume":"145","author":"Britt","year":"2004","journal-title":"Endocrinology"},{"key":"2020071612135162200_B33","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1095\/biolreprod50.6.1238","article-title":"M\u00fcllerian inhibiting substance gene expression in the cycling rat ovary correlates with recruited or Graafian follicle selection","volume":"50","author":"Hirobe","year":"1994","journal-title":"Biol Reprod"},{"key":"2020071612135162200_B34","doi-asserted-by":"crossref","first-page":"4951","DOI":"10.1210\/endo.136.11.7588229","article-title":"Anti-m\u00fcllerian hormone and anti-m\u00fcllerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle, and gonadotropin-induced follicle growth","volume":"136","author":"Baarends","year":"1995","journal-title":"Endocrinology"},{"key":"2020071612135162200_B35","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1530\/rep.0.1240601","article-title":"Regulation of ovarian function: the role of anti-M\u00fcllerian hormone","volume":"124","author":"Durlinger","year":"2002","journal-title":"Reproduction"},{"key":"2020071612135162200_B36","doi-asserted-by":"crossref","first-page":"4426","DOI":"10.1093\/emboj\/17.15.4426","article-title":"Mitogen and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2\/p38, and may mediate activation of CREB","volume":"17","author":"Deak","year":"1998","journal-title":"EMBO J"},{"key":"2020071612135162200_B37","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1128\/MCB.22.8.2871-2881.2002","article-title":"MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts","volume":"22","author":"Wiggin","year":"2002","journal-title":"Mol Cell Biol"},{"key":"2020071612135162200_B38","doi-asserted-by":"crossref","first-page":"5735","DOI":"10.1073\/pnas.1321404111","article-title":"Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice","volume":"111","author":"Wang","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612135162200_B39","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1210\/endo.133.2.8344215","article-title":"Hormonal regulation, localization, and functional activity of the progesterone receptor in granulosa cells of rat preovulatory follicles","volume":"133","author":"Natraj","year":"1993","journal-title":"Endocrinology"},{"key":"2020071612135162200_B40","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1210\/endo.132.6.8504742","article-title":"Regulation of progesterone receptor gene expression and growth in the rat uterus: modulation of estrogen actions by progesterone and sex steroid hormone antagonists","volume":"132","author":"Kraus","year":"1993","journal-title":"Endocrinology"},{"key":"2020071612135162200_B41","doi-asserted-by":"crossref","first-page":"3247","DOI":"10.1210\/en.2005-0213","article-title":"Estrogen receptor-\u03b2 is critical to granulosa cell differentiation and the ovulatory response to gonadotropins","volume":"146","author":"Couse","year":"2005","journal-title":"Endocrinology"},{"key":"2020071612135162200_B42","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1095\/biolreprod.102.004952","article-title":"Specificity of the cyclic adenosine 3\u2032, 5\u2032-monophosphate signal in granulosa cell function","volume":"67","author":"Conti","year":"2002","journal-title":"Biol Reprod"},{"key":"2020071612135162200_B43","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1210\/endo.141.7.7569","article-title":"Luteinizing hormone induces mouse vas deferens protein expression in the murine ovary","volume":"141","author":"Brockstedt","year":"2000","journal-title":"Endocrinology"},{"key":"2020071612135162200_B44","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1210\/endo.142.7.8232","article-title":"Gonadotropin regulation of NGFI-B messenger ribonucleic acid expression during ovarian follicle development in the rat","volume":"142","author":"Park","year":"2001","journal-title":"Endocrinology"},{"key":"2020071612135162200_B45","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1210\/me.2005-0504","article-title":"Paracrine and autocrine regulation of epidermal growth factor-like factors in cumulus oocyte complexes and granulosa cells: key roles for prostaglandin synthase 2 and progesterone receptor","volume":"20","author":"Shimada","year":"2006","journal-title":"Mol Endocrinol"},{"key":"2020071612135162200_B46","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1210\/endo-121-5-1892","article-title":"Ovarian thecal\/interstitial cells produce an epidermal growth factor-like substance","volume":"121","author":"Skinner","year":"1987","journal-title":"Endocrinology"},{"key":"2020071612135162200_B47","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1095\/biolreprod.102.009035","article-title":"Expression of progesterone receptor (PR) A and B isoforms in mouse granulosa cells: stage-dependent PR-mediated regulation of apoptosis and cell proliferation","volume":"68","author":"Shao","year":"2003","journal-title":"Biol Reprod"},{"key":"2020071612135162200_B48","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1210\/me.2002-0435","article-title":"Phosphodiesterase regulation is critical for the differentiation and pattern of gene expression in granulosa cells of the ovarian follicle","volume":"17","author":"Park","year":"2003","journal-title":"Mol Endocrinol"},{"key":"2020071612135162200_B49","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1023\/A:1024181203729","article-title":"The role of sFRP4, a secreted frizzled-related protein, in ovulation","volume":"8","author":"Drake","year":"2003","journal-title":"Apoptosis"},{"key":"2020071612135162200_B50","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.2353\/ajpath.2010.090465","article-title":"Secreted frizzled-related protein 4: an angiogenesis inhibitor","volume":"176","author":"Muley","year":"2010","journal-title":"Am J Path"},{"key":"2020071612135162200_B51","doi-asserted-by":"crossref","first-page":"4597","DOI":"10.1210\/en.2003-0048","article-title":"Expression and localization of secreted frizzled-related protein-4 in the rodent ovary: evidence for selective up-regulation in luteinized granulosa cells","volume":"144","author":"Hsieh","year":"2003","journal-title":"Endocrinology"},{"key":"2020071612135162200_B52","doi-asserted-by":"crossref","first-page":"1203S","DOI":"10.1093\/ajcn\/54.6.1203s","article-title":"Molecular basis for the deficiency in humans of gulonolactone oxidase, a key enzyme for ascorbic acid biosynthesis","volume":"54","author":"Nishikimi","year":"1991","journal-title":"Am J Clin Nutr"},{"key":"2020071612135162200_B53","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1095\/biolreprod52.2.262","article-title":"Ascorbic acid and fertility","volume":"52","author":"Luck","year":"1995","journal-title":"Biol Reprod"},{"key":"2020071612135162200_B54","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1248\/bpb.b13-00309","article-title":"Senescence marker protein-30\/gluconolactonase expression in the mouse ovary during gestation","volume":"36","author":"Kagami","year":"2013","journal-title":"Biol Pharm Bull"},{"key":"2020071612135162200_B55","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1161\/CIRCULATIONAHA.111.064030","article-title":"Endothelial cell-specific FGD5 involvement in vascular pruning defines neovessel fate in mice","volume":"125","author":"Cheng","year":"2012","journal-title":"Circulation"},{"key":"2020071612135162200_B56","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s00427-003-0377-x","article-title":"An enhancer-trap LacZ transgene reveals a distinct expression pattern of kinesin family 26B in mouse embryos","volume":"214","author":"Marikawa","year":"2004","journal-title":"Dev Genes Evol"},{"key":"2020071612135162200_B57","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1385\/ENDO:13:1:81","article-title":"mRNA expression of Phex in mice and rats. The effect of low phosphate diet","volume":"13","author":"Meyer","year":"2000","journal-title":"Endocrine"},{"key":"2020071612135162200_B58","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/1477-7827-9-72","article-title":"Differential gene expression of serine protease inhibitors in bovine ovarian follicle: possible involvement in follicular growth and atresia","volume":"9","author":"Hayashi","year":"2011","journal-title":"Reprod Biol Endocrinol"},{"key":"2020071612135162200_B59","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1002\/mrd.20883","article-title":"Regulation of granulosa and theca cell transcriptomes during ovarian antral follicle development","volume":"75","author":"Skinner","year":"2008","journal-title":"Mol Reprod Dev"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/157\/5\/2093\/8998725\/endo2093.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/157\/5\/2093\/8998725\/endo2093.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T19:35:19Z","timestamp":1594928119000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/157\/5\/2093\/2422930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,26]]},"references-count":59,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,5,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2015-1701","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,26]]}}}