{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T08:17:05Z","timestamp":1771229825109,"version":"3.50.1"},"reference-count":64,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,11,1]]},"abstract":"<jats:p>Polycystic ovarian syndrome (PCOS) is the leading cause of infertility in reproductive-aged women with the majority manifesting insulin resistance. To delineate the causes of insulin resistance in women with PCOS, we determined changes in the mRNA expression of insulin receptor (IR) isoforms and members of its signaling pathway in tissues of adult control (n = 7) and prenatal testosterone (T)-treated (n = 6) sheep (100 mg\/kg twice a week from d 30\u201390 of gestation), the reproductive\/metabolic characteristics of which are similar to women with PCOS. Findings revealed that prenatal T excess reduced (P &amp;lt; 0.05) expression of IR-B isoform (only isoform detected), insulin receptor substrate-2 (IRS-2), protein kinase B (AKt), peroxisome proliferator-activated receptor-\u03b3 (PPAR\u03b3), hormone-sensitive lipase (HSL), and mammalian target of rapamycin (mTOR) but increased expression of rapamycin-insensitive companion of mTOR (rictor), and eukaryotic initiation factor 4E (eIF4E) in the liver. Prenatal T excess increased (P &amp;lt; 0.05) the IR-A to IR-B isoform ratio and expression of IRS-1, glycogen synthase kinase-3\u03b1 and -\u03b2 (GSK-3\u03b1 and -\u03b2), and rictor while reducing ERK1 in muscle. In the adipose tissue, prenatal T excess increased the expression of IRS-2, phosphatidylinositol 3-kinase (PI3K), PPAR\u03b3, and mTOR mRNAs. These findings provide evidence that prenatal T excess modulates in a tissue-specific manner the expression levels of several genes involved in mediating insulin action. These changes are consistent with the hypothesis that prenatal T excess disrupts the insulin sensitivity of peripheral tissues, with liver and muscle being insulin resistant and adipose tissue insulin sensitive.<\/jats:p>","DOI":"10.1210\/en.2010-0666","type":"journal-article","created":{"date-parts":[[2010,9,16]],"date-time":"2010-09-16T01:47:29Z","timestamp":1284601649000},"page":"5165-5173","source":"Crossref","is-referenced-by-count":48,"title":["Developmental Programming: Differential Effects of Prenatal Testosterone Excess on Insulin Target Tissues"],"prefix":"10.1210","volume":"151","author":[{"given":"Shadia E.","family":"Nada","sequence":"first","affiliation":[{"name":"Departments of Pediatrics (S.E.N., V.P.), University of Michigan, Ann Arbor, Michigan 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert C.","family":"Thompson","sequence":"first","affiliation":[{"name":"Departments of Psychiatry (R.C.T.), University of Michigan, Ann Arbor, Michigan 48109"},{"name":"Departments of the Reproductive Sciences Program (R.C.T., V.P.), University of Michigan, Ann Arbor, Michigan 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasantha","family":"Padmanabhan","sequence":"first","affiliation":[{"name":"Departments of Pediatrics (S.E.N., V.P.), University of Michigan, Ann Arbor, Michigan 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2010,9,15]]},"reference":[{"key":"2020071612270417200_R1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1056\/NEJM199509283331307","article-title":"Polycystic ovary syndrome.","volume":"333","author":"Franks","year":"1995","journal-title":"N Engl J Med"},{"key":"2020071612270417200_R2","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1210\/jc.2003-032046","article-title":"The prevalence and features of the polycystic ovary syndrome in an unselected 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