Effects of sex steroids on the regulation of pituitary gonadotropins in the pituitary and hypothalamus

Abstract Sex steroids play a pivotal role in the control of the hypothalamic-pituitary-gonadal axis. In this study, we examined how the sex steroids estradiol (E2), progesterone (P4), and dihydrotestosterone (DHT) influence the synthesis of three pituitary gonadotropin subunits in a pituitary gonadotroph cell model (LβT2 cells) in vitro and ovary-intact rats in vivo. The effects of sex steroids on Kiss1 gene expression in the hypothalamus were also examined in ovary-intact rats. E2 increased common glycoprotein alpha (Cga) and luteinizing hormone beta (Lhb) subunit promoter activity as well as their mRNA expression. Although gonadotropin subunit promoter activity was not modulated by P4, Cga and Lhb mRNA expression was increased by P4. DHT inhibited Cga and Lhb mRNA expression with a concomitant decrease in their promoter activity. During the 2-week administration of exogenous E2 to ovary-intact rats, the estrous cycle, which was determined by vaginal smears, was disrupted. P4 or DHT administration completely eliminated the estrous cycle in rats. Protein expression of all three gonadotropin subunits within the pituitary gland was inhibited by E2 or P4 treatment in vivo; however, DHT reduced Cga expression but did not modulate Lhb or follicle-stimulating hormone beta subunit expression. E2 administration significantly repressed Kiss1 mRNA expression in a posterior hypothalamic region that included the arcuate nucleus. P4 and DHT did not modulate Kiss1 mRNA expression in this region. In contrast, P4 administration significantly inhibited Kiss1 mRNA expression in a posterior region of the hypothalamus that included the anteroventral periventricular nucleus. Our findings suggest that sex steroids have different effects in the hypothalamus and pituitary gland.