Hepatic binding of human and bovine growth hormones and ovine prolactin in the dwarf "little" mouse

Abstract

Binding of human (hGH) and bovine (bGH) GH and ovine PRL (oPRL) has been compared in liver membranes from GH-deficient dwarf "little" mice (lit/lit) and their normal-sized littermates (lit/+). Binding of [125I]hGH to lit/lit membranes was dependent on time, temperature, and membrane concentration and was reversible. Scatchard plots of the binding of [125I]hGH to male and female lit/lit and lit/+ membranes were linear, with no significant differences between binding affinities (overall mean +/- SE, 1.42 +/- 0.27 X 10(9) M-1; n = 24). The hormonal specificity of binding was complex, with hGH being displaced by both somatotropic (bGH) and lactogenic (oPRL) competitors, indicating the presence of a mixed population of receptors. This conclusion was supported by the specific binding of both [125I]bGH and [125I]oPRL to membranes from male and female lit/lit and lit/+ mice. No differences in the specific binding of [125I]bGH to any membrane type was observed, indicating that GH receptors were at normal levels in lit/lit mice despite their deficiency of pituitary and serum GH. A sex difference in hGH and oPRL binding was seen only in normal (lit/+) mice. Male and female lit/lit mice exhibited the same degree of binding as normal female mice. These studies have demonstrated that dwarf little mice have normal levels of hepatic GH and PRL receptors, with binding characteristics not different from those of normal mice. Thus, it would appear that the mechanism of regulation of GH receptors by GH itself is different in this animal model of GH deficiency than in the Snell dwarf mouse and the hypophysectomized rat, where GH receptor levels are very low or absent. The failure of lit/lit mice to grow normally despite normal levels of GH receptor raises questions regarding the site and mechanism of the growth defect in the little mouse.