Effects of chronic hyperandrogenism and/or administered central nervous system insulin on ovarian manifestation and gonadotropin and steroid secretion

Abstract

Objective: Polycystic ovarian syndrome is characterized by hyperandrogenism and insulin resistance. We studied the effects of central hyperinsulinemia and peripheral hyperandrogenism on gonadotropin secretion, steroid secretion, and ovarian histology in female rats.

Design: Experimental in vivo animal study.

Setting: University research center.

Animal(s): 250-300 g female Wistar rats.

Intervention(s): Insertion of testosterone pellets and/or administration of intracerebroventricular (ICV) insulin.

Main outcome measure(s): Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels before and after GnRH administration; testosterone, insulin, and glucose levels; and ovarian histology.

Result(s): Compared with control, rats with testosterone implant had a lower LH and higher FSH while rats with testosterone plus insulin had a higher FSH. Intracerebroventricular (ICV) insulin alone increased LH in response to GnRH. Ovarian histology indicated that testosterone-implanted rats had larger ovaries and an increased number of cystic follicles >50 microm as well as substantial theca enlargement. The administration of testosterone did not alter serum insulin, and ICV insulin did not increase testosterone levels.

Conclusion(s): We suggest that ICV insulin acts either directly or indirectly to increase the LH responsiveness to GnRH. ICV insulin arrested the maturation of follicles leading to an increase in the number of small follicles. Peripheral androgens stimulated theca enlargement with cystic follicles. The combination of ICV insulin and peripheral androgens attenuated ovarian histologic changes and gonadotropin secretion. Thus, central hyperinsulinemia and peripheral hyperandrogenism may play a role in gonadotropin secretion as well as ovarian morphology.