Homologous induction of growth hormone receptors in cultured rat hepatocytes.
The administration of growth hormone (GH) to animals has been reported to induce GH receptors in liver and adipose tissue. However, GH addition to cultured fibroblasts and lymphoblasts downregulated GH receptors, suggesting an indirect mechanism for GH upregulation of its receptors in vivo. We evaluated the direct role of GH by adding it to rat hepatocytes cultured in serum-free medium supplemented as previously described (Barash et al. (1988) Endocrinology 122, 1151-1158). After 3 days in culture the initial 125I-bGH specifically bound (0.18 ng per mg protein) had declined 5-fold. Binding continued to decrease thereafter to 0.008 ng by day 9 of culture. When added after 3 days in culture both hGH and bGH induced GH receptors. The maximum level (0.1 ng/mg protein) was attained 2 days later (day 5 of culture) and remained at this plateau through day 9 of culture. Induction occurred with 10 ng/ml hGH and was maximal (4- to 12-fold control) at 250 ng/ml. At a supramaximal dose of 1000 ng/ml hGH downregulated GH receptor. GH receptor induction was equally seen with hGH, bGH and rGH and did not occur on incubation with oPRL or ACTH. Thyroxine (1 X 10(-5) M) augmented 125I-bGH binding to levels 3-fold those of control but did not further augment the inductive effect of GH alone. We conclude that hepatic GH receptors are upregulated by GH acting through its own receptor. The induction occurs rapidly without a lag phase. The failure to restore fully receptor levels to those seen in freshly prepared hepatocytes implies a role for other modulating factor(s).
Barash
I
I
Division of Endocrinology, Royal Victoria Hospital, Montreal, Canada.
Posner
B I
BI
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D013006:Growth Hormone / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D011388:Prolactin / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011981:Receptors, Prolactin / Q000096:biosynthesis; D011986:Receptors, Somatotropin / Q000096:biosynthesis*; D013974:Thyroxine / Q000494:pharmacology
D011981:Receptors, Prolactin; D011986:Receptors, Somatotropin; D011388:Prolactin; D013006:Growth Hormone; D013974:Thyroxine