Differences in the developmental patterns of somatotrophic and lactogenic receptors in rabbit liver cytosol

These studies have examined the ontogeny of specific GH- and PRL-binding proteins in rabbit liver cytosol across the fetal, early neonatal, and adult periods. The precise hormonal specificity of binding of the somatotropic/lactogenic ligand, [125I]human GH, was determined by displacement with monoclonal antibodies against either rabbit mammary gland PRL receptors or liver GH receptors. The developmental changes were evaluated by gel filtration chromatography, which allowed a measure of both the extent of binding and the molecular size (Mr). Scatchard analysis indicated that fetal liver cytosol contained mostly high affinity PRL receptors (Ka, 13.78 +/- 0.98 nM-1; capacity, 127 +/- 24.0 fmol/g tissue; mean +/- SEM; n = 5) and was low in GH-specific binding. This contrasts markedly with adult liver cytosol, which is a rich source of GH receptors (Ka, 2.44 nM-1; capacity, 20,765 fmol/g tissue), but is low in PRL-specific binding. Despite the deficiency of GH receptors in fetal liver, an abundant receptor-like GH-binding protein was present in fetal serum. Of several fetal tissue cytosols examined, only the placenta contained significant GH-specific binding; no tissues other than liver contained PRL-specific binding. After parturition PRL receptors in liver cytosol increased and predominated up until day 3 (Ka, 27.97 +/- 6.27 nM-1; capacity, 495 +/- 95.09 fmol/g tissue; n = 7), a period during which GH-specific binding was increasing only slightly. By day 6 a striking switch-over occurred, and GH receptors, which had a 4-fold lower affinity, became predominant (Ka, 6.89 +/- 0.63 nM-1; capacity, 600 +/- 47 fmol/g tissue; n = 5), while PRL-specific binding fell dramatically to levels observed in adult liver cytosol. After day 6 GH receptors increased steadily, reaching the high levels observed in adulthood by 2 months (Ka, 3.95 nM-1; capacity, 16,300 fmol/g tissue; n = 2), while PRL-specific binding appeared to change little. Structural and immunological analyses of the cytosolic GH and PRL receptors in the fetal/early neonatal period revealed similarities with the adult liver cytosolic GH receptor and mammary gland cytosolic PRL receptor, respectively. The increase in GH receptors on day 6 was clearly illustrated by cross-linking studies which showed the emergence of a GH-specific binding protein structurally distinct from PRL-specific binding proteins. These studies have demonstrated that in the rabbit major changes occur in the GH/PRL receptor profile during the early period of growth and suggest that important developmental changes occur in the requirement for GH and/or PRL action during this period.