Endocrine Abstracts

Different animal models have been used to study the postnatal effect of a prenatal exposure to an androgen excess on the female offspring. We have established a sheep model to test the hypothesis that the intrauterine environment of the PCOS mother may play a role in the etiology of the PCOS. In this regard, our sheep model for the study of PCOS has the advantage that provides mainly an androgenized milieu to the fetus in comparison to pregnant PCOS women who offers a hyperandrogenic and hyperinsulinemic intrauterine environment to the fetus. Previous results from our laboratory have demonstrated that female sheep born to mothers receiving testosterone (T) during part of their pregnancy exhibit features from early postnatal life until adulthood resembling those of PCOS women. In the present work the programming effect of prenatal T on the IS was explored in adult females born to T treated mothers (T-females), and born to untreated mothers (C-females). Our aim was to establish if exogenous T may exacerbate the insulin resistance due to programming effect of prenatal exposure to T. Both groups were injected with T, twice weekly (40 mg per dose), for 8 weeks, beginning at 30 weeks of age. Females were estrous synchronized with prostaglandin and 48 hours after the last T dose, an IVGTT was carried out. On the day of the IVGTT, there was no difference in plasma concentration of estradiol, progesterone and T between groups. IS indexes were calculated with the plasma insulin and glucose concentrations during the IVGTT. Plasma levels of glucose were not different during the IVGTT but T-females secreted more insulin (P<0.05) than C-females. The ratio insulin/glucose before the IVGTT tended to be higher in T-females (P=0.054) and the IS Index-C tended to be lower in T-females compared to C-females (P=0.054). Results show that T administration to T-females amplifies the effect of a glucose challenge on the insulin secretion compared to C-females, suggesting an exacerbation of the insulin resistance induced by fetal programming.