Endocrine Abstracts

PCOS is one of the most common cause of infertility in women during their reproductive years. High proportion of women with PCOS develop IR in peripheral tissues like skeletal muscle and adipose tissue, which may begin at the adolescent years when young women exhibit an increase in circulanting androgens. Studies in women with PCOS and animal models of PCOS have suggested alterations in insulin signaling pathways in skeletal muscle and adipose tissue. However, at the present time, it does not exist evidence between alteration on insulin signaling in endocrine pancreas and its correlative effect on peripheral insulin sensitivity tissues. Previous results from our group have demonstrated that female sheep born to mothers receiving T between days 30 to 120 of gestation exhibit features of insulin resistance from early postnatal stage to adulthood. In the present work, the reprogramming effect of prenatal T on adipose tissue morphology and the insulin signaling in adipose tissue was studied in postpubertal females born to untreated mothers (C-females) and born to T treated mothers (T-females), subjected to a further T administration at the pubertal age. Our aim was to identify if a further T treatment during pubertal development could affect pancreas and adipose tissue. Postpubertal C-females and T-females (38 weeks of age) were sacrificed after an eight week chronic T administration and samples of pancreas, SAT (subcutaneous adipose tissue) and VAT (visceral adipose tissue) were collected. The morphological analysis of the adipose tissue included measurements of area, perimeter, diameter and adipocyte number/mm². Results showed no difference (P≥0,05) in morphological parameters between C- and T-females in SAT. However in VAT, the adipocyte area, perimeter, diameter was higher in T-females than in C-females. Gene expression of IR, IRS-1, PI3K, PKC in pancreas showed similar expression in T-females (P≥0.05) compared to that of C-females, while, on the contrary, the Akt and GLUT4 RNAm was lower in T-females (P<0.05). Interesting, IRS-2 transcript showed a tendency to a higher expression (P≥0.05) in T-females. qPCR assays of SAT showed a transcriptional repression of IRS-1, PKC, Akt and GLUT4 (P<0.05) in T-females. In VAT, insulin signaling did not show effect on expression of pathways elements, except higher Akt levels of RNAm in T-females (P<0.05). Results suggest that prenatal and postnatal exposure to T affects the insulin signaling on beta cells during post pubertal development and induced a dual effect in adipose tissue at the transcriptional and morphological levels.