{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:22:40Z","timestamp":1791249760353,"version":"4.1.0"},"reference-count":88,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:p>Prenatal T excess induces maternal hyperinsulinemia, early puberty, and reproductive\/metabolic defects in the female similar to those seen in women with polycystic ovary syndrome. This study addressed the organizational\/activational role of androgens and insulin in programming pubertal advancement and periovulatory LH surge defects. Treatment groups included the following: 1) control; 2) prenatal T; 3) prenatal T plus prenatal androgen antagonist, flutamide; 4) prenatal T plus prenatal insulin sensitizer, rosiglitazone; 5) prenatal T and postnatal flutamide; 6) prenatal T and postnatal rosiglitazone; and 7) prenatal T and postnatal metformin. Prenatal treatments spanned 30\u201390 days of gestation and postnatal treatments began at approximately 8 weeks of age and continued throughout. Blood samples were taken twice weekly, beginning at approximately 12 weeks of age to time puberty. Two-hour samples after the synchronization with prostaglandin F2\u03b1 were taken for 120 hours to characterize LH surge dynamics at 7 and 19 months of age. Prenatal T females entered puberty earlier than controls, and all interventions prevented this advancement. Prenatal T reduced the percentage of animals having LH surge, and females that presented LH surge exhibited delayed timing and dampened amplitude of the LH surge. Prenatal androgen antagonist, but not other interventions, restored LH surges without normalizing the timing of the surge. Normalization of pubertal timing with prenatal\/postnatal androgen antagonist and insulin sensitizer interventions suggests that pubertal advancement is programmed by androgenic actions of T involving insulin as a mediary. Restoration of LH surges by cotreatment with androgen antagonist supports androgenic programming at the organizational level.<\/jats:p>","DOI":"10.1210\/en.2015-1235","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T17:00:32Z","timestamp":1430240432000},"page":"2678-2692","source":"Crossref","is-referenced-by-count":51,"title":["Developmental Programming: Prenatal and Postnatal Androgen Antagonist and Insulin Sensitizer Interventions Prevent Advancement of Puberty and Improve LH Surge Dynamics in Prenatal Testosterone-Treated Sheep"],"prefix":"10.1210","volume":"156","author":[{"given":"Vasantha","family":"Padmanabhan","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almudena","family":"Veiga-Lopez","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 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