TY - JOUR
T1 - Ontogenesis of growth hormone (gh)-responsive hepatic gene products
T2 - Lack of correlation with hepatic gh receptor content
AU - Berry, Susan A.
AU - Manthei, Robin D.
AU - Seelig, Steven
PY - 1986/11
Y1 - 1986/11
N2 - 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.
AB - 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.
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U2 - 10.1210/endo-119-5-2290
DO - 10.1210/endo-119-5-2290
M3 - Article
C2 - 3769871
AN - SCOPUS:0022997449
VL - 119
SP - 2290
EP - 2296
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 5
ER -