Ontogenesis of growth hormone (gh)-responsive hepatic gene products: Lack of correlation with hepatic gh receptor content

The ontogenesis of hepatic GH receptor content is postulated as a major determinant of expression of hepatic GH-responsive gene products, since the ontogeny of the receptors and the responsive gene products, somatomedin-C, somatomedin-binding protein, and GH-responsive acidic protein, have similar qualitatively ontogenetic patterns. Two-dimensional gel electrophoresis of in vitro synthesized [³⁵S]methionine-labeled proteins formed in the cell-free mRNA-dependent rabbit reticulocyte lysate system in response to hepatic RNA was used to quantitate the ontogenetic changes in a family of five GH-responsive gene products (S₃, S₁₁, S₁₅, S₁₆, and S₂₀). These gene products were altered 2- to 12-fold by the administration of methionyl-human GH to adult hypophysectomized animals and were not altered by the combined administration of T₄, corticosterone, and dihydrotestosterone. The translational activity of three of the five products (S₃, S₁₅, and S₂₀) in animals younger than 15 days ranged from 1–12% of the values observed in normal adults and was consistent with diminished GH action. The translational activities of two mRNA sequences (S₁₁ and S₁₆) were not consistent with diminished GH action in the newborn animal. In the newborn animal, S₁₁, induced 3-fold by GH in the adult animal, was 7.4 times the level observed in the adult. During the time of increasing GH receptor content (2–35 days), S₁₆, attenuated by GH 2-fold in the adult, increased 6-fold. Injection of GH from days 2 through 11 augmented S₂₀ and D₂ (a hormonally nonresponsive, developmentally dependent product) 2-fold. The combined administration from days 2 through 11 of GH, T₄, and corticosterone augmented S₁₆ 1.8-fold, a response paradoxical to that in the adult animal, but consistent with advancing maturation of the liver. We conclude that GH receptor content is not the sole determinant for the ontogenetic expression of GH-responsive products and that important alternate mechanisms exist for their regulation. In addition, GH, along with T₄ and corticosterone, appear to modulate the rate at which adult levels of some mRNA sequences are achieved.