17 beta-estradiol induces somatostatin (SRIF) inhibition of prolactin release and regulates SRIF receptors in rat anterior pituitary cells

Abstract

The role of 17 beta-estradiol (E2) in the induction of an inhibitory effect of somatostatin (SRIF) on PRL release and in the regulation of SRIF receptors was analyzed in rat anterior pituitary cells. SRIF exerts a moderate inhibitory effect on basal PRL release from cultured pituitary cells prepared from normal rats. The inhibitory effect of SRIF was weakened when the cells were prepared from castrated rats, but was strengthened in cells from E2-treated rats. When cells from ovariectomized rats were cultured with charcoal-treated sera in the absence of E2, SRIF affected neither basal PRL release nor the increased PRL release elicited by TRH, (Bu)2cAMP, or vasoactive intestinal peptide. However, in cells cultured with E2 (10(-9) M) for more than 12 h, SRIF decreased basal as well as secretagogue-stimulated PRL release. Enhancement of both the sensitivity and magnitude of the inhibitory effect of SRIF appeared dependent upon the length of the preincubation and the E2 concentration. On the other hand, an inhibitory effect of SRIF on GH release was unaffected by castration, E2 administration in vivo, or E2 treatment in vitro. Dihydrotestosterone (10(-6) M) produced an effect similar to that of E2, but other steroids tested did not. Binding studies demonstrated that the specific binding of [125I-Tyr11]SRIF was saturable, with a Kd of 99 pM and a maximum binding capacity of 89.4 fmol/mg protein in pituitary membranes from control rats, and a Kd of 45 pM and a maximum binding capacity of 305.2 fmol/mg protein in membranes from rats primed with E2 for 4 weeks. Apparent Ki values for native SRIF in both membranes were similar. Treatment of pituitary cells with E2 for 8 days in vitro in culture produced a 2-fold increase in the number of binding sites. These results demonstrate that E2 acts on mammotrophs at the pituitary level, rendering them sensitive to SRIF, probably by increasing the number of SRIF receptor sites.