PITUITARY REGULATION OF HUMAN GROWTH-HORMONE BINDING-SITES IN RAT-LIVER MEMBRANES

The binding of 125I-human growth hormone (hGH) to crude 100,000 .times. g membrane preparations from rat liver, and factors which might regulated the capacity and affinity of hGH binding sites were studied. Membrane preparations from livers of pregnant rats bound between 8% and 18% of the 125I-hGH initially added, and 70%-80% of that bound was displaced by 1 .mu.g of unlabeled hGH. Human prolactin (hPrl) displaced 125I-hGH in a manner parallel to hGH itself but with about 1/3 the potency. Ovine, porcine and rat Prl, and rat and bovine GH were much less effective. Scatchard analysis of specific hGH binding by a variety of different rat liver membrane preparations revealed a single order of binding site in each case with a binding affinity of 0.93-1.62 .times. 109 M-1. Membranes from pregnant rats had twice the binding capacity of membranes from nonpregnant females rats, and about 6.times. the capacity of sites present in preparations from normal adult male rats and hypophysectomized (Hx) male or female rats. Female or male rats with extremely high circulating GH and Prl levels, due to the presence of transplantable GH/Prl secreting pituitary tumors showed a significantly greater binding capacity than did the pregnant rats. Estradiol (E2) treatment (25 .mu.g/day for 10-12 days) of normal male rats led to an increase in specific hGH binding. Treatment of hypophysectomized male rats with bovine GH (100 or 500 .mu.g/day) .+-. E2 (25 .mu.g/day) for 5-10 days stimulated both body weight gain and the incorporation of sulfate by cartilage from the treated rats, but no significant increase was observed in the characteristics of 125I-hGH binding. High levels of E2, GH and/or Prl play an important role in the regulation of hGH binding sites in rat liver membranes. The restoration of binding sites in liver from hypophysectomized rats apparently requires additional factors which are as yet unidentified. The role of the hGH binding sites in the physiological actions of GH also remains to be determined.