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
| Autor: | Jacob Moeller, Vasantha Padmanabhan, Carol Herkimer, Bachir Abi Salloum, Evan M. Beckett, Rohit Sreedharan, Almudena Veiga-Lopez |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class medicine.medical_treatment Estrous Cycle Flutamide Fetal Development Rosiglitazone chemistry.chemical_compound Endocrinology Pregnancy Internal medicine medicine Hyperinsulinemia Animals Hypoglycemic Agents Testosterone Sexual Maturation Sheep Domestic Original Research Sheep business.industry Insulin Androgen Antagonists Luteinizing Hormone medicine.disease Androgen Polycystic ovary Metformin chemistry Prenatal Exposure Delayed Effects Androgens Female Thiazolidinediones business medicine.drug Polycystic Ovary Syndrome |
| Zdroj: | Endocrinology. 156(7) |
| ISSN: | 1945-7170 |
| Popis: | 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 30–90 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 F2α 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. |
| Databáze: | OpenAIRE |
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