Hepatic steroid hydroxylating enzymes are controlled by the sexually dimorphic pattern of growth hormone secretion in normal and dwarf rats.
In rats, the onset of the sexually dimorphic pattern of growth hormone (GH) secretion and increased hepatic GH-binding capacity at puberty are temporally correlated with the sex-dependent expression of some hepatic cytochrome P450 enzymes involved in steroid metabolism. There are indications that the expression of the GH receptor gene itself is dependent on the sexually differentiated pattern of GH secretion. However, the molecular mechanisms by which a given pattern of GH secretion turns on a specific set of genes in the hepatocyte are not yet understood. Studies of the cytochrome P450 2C gene subfamily in hypophysectomized rats and isolated hepatocytes suggest that one major mechanism of GH action in the liver occurs through modulation of gene transcriptional initiation. The occurrence, in dwarf rats and in rats treated neonatally with monosodium glutamate, of sex differences in GH secretion and liver steroid metabolism typical of normal rats, in spite of a 95% reduction in pituitary GH levels, is compatible with the notion that extremely low levels of circulating GH are sufficient to regulate the expression of liver steroid-metabolizing enzymes. This, together with the fact that single daily subcutaneous injections of GH are sufficient to masculinize the liver of a hypophysectomized rat, indicates that neither the amplitude nor the frequency of the GH pulse is recognized as male or female by the hepatocyte, but rather the complete and prolonged suppression (in males) or the persistence (in females) of circulating GH during the trough period after a GH surge.
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Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital, Sweden.
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Wells
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Robinson
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Gustafsson
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D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004392:Dwarfism / Q000503:physiopathology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D013006:Growth Hormone / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases