Effects of Hypophysectomy, Ovariectomy, and Cycloheximide on Specific Binding Sites for Lactogenic Hormones in Rat Liver

Abstract

Specific binding sites for lactogenic hormones are present at much greater levels in the liver membranes of female than of male rats. [125I]Iodo-hGH [human growth hormone] was used to study binding sites specific for lactogenic hormones in liver membranes. In male rats, a single injection of 2 mg estradiol (E2) valerate induced these binding sites. The induction was maximal by 9-12 days and was dose-dependent. Ovariectomy significantly reduced the specific binding of [125I]iodo-hGH from 9.7 .+-. 0.7% in sham-operated to 6.9 .+-. 0.3% in experimental rats (P < 0.01) without a change in affinity. Fluctuations in specific binding of [125I]iodo-hGH were observed at different stages of the estrous cycle. Binding at estrus and diestrus I was significantly greater than at diestrus II and proestrus (P < 0.05). The disappearance of binding sites following hypophysectomy was rapid, declining from 13.2 .+-. 1.2% in intact rats to 6.0 .+-. 0.8% and 2.2 .+-. 0.4% 14 and 48 h, respectively, after surgery. In contrast, binding of insulin was slightly increased after hypophysectomy. Anti-estrogens (clomiphene, ICI 46,474, and nafoxidine) prevented the induction of binding sites in male rats given E2. A single injection of 200 .mu.g cycloheximide 11 days after an injection of 2 mg E2-valerate reduced binding by more than 90% in 3 h with a return to control levels by 48 h. The maximal decline in insulin binding was 54% during this entire period. These studies suggest that endogenous estrogen plays a role in regulating hepatic binding sites for lactogenic hormones. The level of these binding sites is critically dependent on the presence of an intact pituitary. The possible rapid turnover of these sites suggests that regulatory influences at the tissue level may have an important role in modulating hormone action.