Binding of human growth hormone to hepatic lactogenic binding sites: regulation by oestrogens and androgens.
The binding of 125I-labelled human growth hormone (HGH) to the 'lactogenic' binding sites of rat liver membranes has been shown to be highly dependent on the oestrogen and androgen status of the membranes has been shown to be highly dependent on the oestrogen and androgen status of the animal from which the membranes were prepared. Oestradiol treatment of either male or female rats induced a highly significant rise in HGH binding. The minimum effective dose used was 2-5 mug/day and the rise in HGH binding was apparent after 4 days of treatment. Folowing cessation of oestradiol treatment of male rats HGH binding declined with a half-time of approximately 9 days. In contrast to the stimulatory effect of oestrogen, treatment of female rats with testosterone propionate (minimum effective dose 100-200 mug/day) led to a marked reduction in HGH binding. The influence of both oestrogens and androgens was confirmed following the removal of endogenous sex steroids by adrenalectomy-ovariectomy of female rats and castration of male rats. Scratchard analysis showed that, with the possible exception of adrenalectomy-ovariectomy, all pharmacologically and physiologically induced changes in HGH specific binding reflected changes in binding site capacity; there were no changes in binding affinity. While earlier studies have indicated that the oestrogen effect is primarily indirect and is mediated by the pituitary gland, the mode of action of the androgens is currently unknown. The relatively slow response of HGH binding to hormonal changes would support an indirect action for both the sex steroids. The stimulatory effect of oestrogens and the inhibitory effect of androgens may provide an explanation for the marked sex difference in HGH binding to rat liver membranes.
D000315:Adrenalectomy; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D002369:Castration; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009708:Nucleotidases / Q000032:analysis; D051381:Rats; D013739:Testosterone / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
D013739:Testosterone; D004958:Estradiol; D013006:Growth Hormone; D009708:Nucleotidases