SEXUALLY DIMORPHIC INTERACTION OF INSULIN-LIKE-GROWTH-FACTOR (IGF)-I AND SEX STEROIDS IN LACTOTROPHS

Anterior pituitary hormone secretion is sexually dimorphic due partial ly to gender differences in the postpubertal hormone environment; howe ver, differences in the pituitary's responsiveness to these signals ma y also play a role, We have used simple and double in situ hybridizati on to determine whether lactotrophs and somatotrophs from male and fem ale rats respond differently in vitro to growth hormone-releasing horm one (GHRH), somatostatin (SS) or insulin-like growth factor (IGF)-I an d whether sex steroids modulate these responses. Cultures were treated with either 17 beta-estradiol (E; 10(-9) M), testosterone (T; 10(-7) M), dihydrotestosterone (DHT; 10-7 M) or vehicle in combination with e ither GHRH (10(-7) M), SS (10(-7) M), IGF-I (10(-7) M) or vehicle. Bas al mRNA levels of GH, prolactin (PRL) and pituitary transcription fact or-1 (Pit-1) did not differ between the sexes. The responses to peptid e hormones alone were similar between the sexes, but not in the presen ce of gonadal steroids, In females, DHT reduced and E increased the st imulatory effect of GHRH and inhibitory effect of SS on GH mRNA levels (two-way ANOVA: P < 0.05), while having no effect in males. An additi ve effect of E and GHRH on PRL mRNA levels was seen only in males. The E induced rise in PRL mRNA levels was completely inhibited by SS in f emales, but only partially so in males (two-way ANOVA: P < 0.001), IGF -I inhibited the E induced rise in PRL and lactotroph Pit-1 mRNA level s only in females, These results suggest that sex steroids modulate th e pituitary's response to hypothalamic and circulating factors differe ntly in males and females and that this may play a role in generating the sexually dimorphic patterns of pituitary hormone secretion.