Glucose regulation of growth hormone receptors in primary cultured rat hepatocytes.
The effects of nutritional factors on the regulation of GH receptors were studied by measuring the specific binding of 125I-human GH to rat hepatocytes cultured in various media. The binding of labeled GH to primary cultured hepatocytes decreased during culture, the extent of the decrease depending on the culture medium. The decreases of GH binding during culture in glucose-poor media (i.e. Williams' medium E, Dulbecco's modified minimum essential medium, and McCoy 5A medium) were significantly more than that in glucose-rich Waymouth's medium MB 752/1 (Waymouth's). In glucose-poor media supplemented with glucose, the extent of decrease of GH binding was comparable to that in Waymouth's. Other hexoses such as D-fructose and D-mannose also significantly reduced the decrease in GH binding. Scatchard plot analysis showed that the effect of glucose in preventing decrease of GH binding was due to change in the number of binding sites without significant change in their affinity. The effect of glucose was additive with that of dexamethasone, which induces GH receptors. Cycloheximide caused almost complete loss of GH binding by cells cultured in the presence of glucose. 2-Deoxyglucose reduced the effect of glucose, but did not affect that of dexamethasone. These results show that glucose counteracts decrease of GH binding sites during culture and suggest that it affects de novo synthesis of GH receptors, presumably through glycosylation of a certain protein that regulates GH receptor gene expression (new protein synthesis). The mechanism of the effect of glucose on induction of GH receptors seems to be different from that of dexamethasone.
Division of Biological Chemistry and Biologicals, National Institute of Hygienic Sciences, Tokyo, Japan.
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Niimi
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Hayakawa
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Tanaka
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Ichihara
D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D003513:Cycloheximide / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000502:physiology*; D013006:Growth Hormone / Q000378:metabolism*; D006601:Hexoses / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011979:Receptors, Pituitary Hormone / Q000378:metabolism*; D013223:Statistics as Topic
D003470:Culture Media; D006601:Hexoses; D011979:Receptors, Pituitary Hormone; D003907:Dexamethasone; D013006:Growth Hormone; D003513:Cycloheximide; D003847:Deoxyglucose; D005947:Glucose