Regulation of Lactogen Specific Binding Sites in Rat Liver: Studies on the Role of Lactogens and Estrogen1

Abstract

Regulation of the lactogen specific binding sites of rat [r] liver was studied in several different high lactogen states. The specific binding of [125I]iodo-hGH [human growth hormone] was determined as a measure of these sites. Hypophysectomy [hypox] of pregnant rats produced a much smaller decrease in hepatic binding of [125I]iodo-hGH than was seen in non-pregnant females. Three different prolactin [PRL] secreting tumors (MtT/F4, MtT/F45, MtT/W5) produced greatly elevated levels of both rPRL and hepatic binding of [125I]iodo-hGH in both male and female rats. The increased binding reflected an increase in the concentration of lactogen specific membrane binding sites. There was no change in the apparent affinity of binding. Hopox of tumor-bearing rats was not followed by a decrease in the concentration of hepatic sites. Pituitary transplants beneath the kidney capsules of hypox rats produced elevated rPRL levels and increased [125I]iodo-hGH specific binding to hepatic membranes. The elevation of serum rPRL preceded the increase in hepatic binding. There was a direct correlation between rPRL levels attained by 8 days after implantation and the level of hepatic binding. Estrogen treatment did not alter this correlation. Hormonal replacement with PRL in combination with various hormones failed to induce the lactogen specific hepatic sites in estrogen treated hypox males, and did not prevent the marked decrease in hepatic binding observed in females following hypox. Chronic elevation of PRL may play a role in inducing lactogen specific binding sites in rat liver. Estrogen''s inductive action seems to be largely effected at the pituitary level.