PRENATAL ANDROGENS DEFEMINIZE ACTIVATION OF GNRH NEURONS IN RESPONSE TO ESTRADIOL STIMULATION

To determine if prenatal androgens prevent activation of GnRH neurons in response to estradiol stimulation, Fos colocalization with GnRH was compared in the brains of normal female lambs, normal males, and andr ogenized females in response to a surge-inducing dose of estradiol, Bl ood samples were collected every 1-2 h for 6 h before estradiol treatm ent up to the time of sacrifice at 17-19 h posttreatment, Following pe rfusion, 60 mu m coronal brain sections were immunostained for Fos (1: 1000, Santa Cruz Biochemicals) and GnRH (1:40,000, LR-1) using NiCl-en hanced and unenhanced DAB, respectively, Although LH secretion increas ed in females before sacrifice, no increase was observed in males or a ndrogenized females.,Despite differences in LH secretion, the number a nd distribution of GnRH neurons was not sexually dimorphic. Moreover, Fos immunostaining was visible throughout steroid-responsive limbic re gions in all three groups of lambs, However, the colocalization of Fos with GnRH was highly sexually dimorphic. In females perfused after th e peak of the LH surge, 65.7% of GnRH neurons in the preoptic area, an terior hypothalamus, and mediobasal hypothalamus expressed Fos, wherea s only 1.7% of GnRH neurons were Fos-positive in males and androgenize d females. These findings indicate that sex differences in the activat ion of GnRH neurons in response to estradiol are determined prenatally through the actions of testosterone.