Interaction of human growth hormone with isolated rat liver cells.

The interaction of 125I-labeled human growth hormone (hGH) with isolated rat liver cells is a specific, time dependent and saturable process. In male rats, one cell binds a maximum of 2000 hormone molecules; the dissociation constant of the cell-hGH interaction is about 3 X 10(-10)M. Liver cells of female rats bind 5 to 10 times more hGH than do those of male rats at equivalent hormone concentrations. Binding of 125I-labeled hGH to liver cells is readily inhibited by native hGH; 50% inhibition occurs at about 2 X 10(-9)M hGH irrespective of sex. In male rats, bovine growth hormone (bGH) is almost as potent as hGH in inhibiting 125I-labeled hGH binding; no displacement occurs with ovine prolactin (oPRL) except at very high (greater than 10(-6)M) concentrations. In female rats, bGH competes less effectively, and oPRL, more effectively, than they do in males; in addition, oPRL demonstrates a higher apparent affinity for the hGH binding sites (4 X 10(-9)M) than does bGH (1 X 10(-8M). These findings suggest that in female rats hGH, unlike bGH, interacts with additional, "lactogenic" binding sites that are distinct from the "growth hormone" binding sites. The 125I-labeled hGH eluted from liver cells as well as that which remains in the incubation medium retains full biological activity, as judged on its ability to bind specifically to liver membranes. Treatment of liver cells by phospholipase A causes a 5-fold increase in cell binding capacity. Liver cells bind about the same amount of hGH as do crude particulate fractions from these cells; this suggests that in the intact cell, binding occurs at relatively accessible sites, presumably localized in the plasma membrane.