Prenatal Androgen Treatment Alters Body Composition and Glucose Homeostasis in Male Rats

Abstract

Prenatal androgen produces many reproductive and metabolic features of polycystic ovary syndrome in female rodents, sheep, and monkeys. We investigated the impact of such prenatal treatment in adult male rats. Pregnant dams received free testosterone (T; aromatizable androgen), dihydrotestosterone (D; nonaromatizable androgen), or vehicle control (C) on embryonic days 16-19. Neither of the prenatal androgen treatments resulted in increased body weight from weaning to age 65 days in males. However, at 65 days, there were significant increases in retroperitoneal (P < 0.001 T versus C; P < 0.05 D versus C), epididymal (P < 0.05 T versus C), and subcutaneous (P < 0.01 T versus C) fat pads in prenatally androgenized males. While both androgens altered body composition, subcutaneous fat depots increased only in T males. T males had elevated glucose levels (P < 0.01) compared to C males. There were no differences among the three groups in insulin sensitivity, circulating lipid and leptin levels, or hepatic triglyceride content. Real-time PCR analysis of insulin signaling pathway genes in retroperitoneal fat revealed a transcriptional downregulation of adipsin and insulin receptor substrate-1 in T and α-1D adrenergic receptor in D compared to C males. We conclude that transient exposure to androgen excess in utero increases body fat in adult male rats. Only T males exhibit increased circulating glucose levels and subcutaneous fat suggesting that these changes may be mediated by aromatization of androgen to estrogen rather than by direct androgenic actions.