Regulation by growth hormone and glucocorticoid of testosterone metabolism in long-term cultures of hepatocytes from male and female rats.
The activities of 2-, 6 beta-, 7 alpha- and 16 alpha-testosterone hydroxylase and 5 alpha-testosterone reductase were measured in intact hepatocytes from male and female rats cultured for 8 days in a modified Waymouth medium supplemented with 0.1 or 1.0 microM dexamethasone with or without addition of 1 microgram/mL growth hormone. During culture of hepatocytes from female rats the activity of the male-specific 16 alpha-testosterone hydroxylase increased. This increase was significantly inhibited at day 8 by 1 microM dexamethasone as well as by growth hormone. Furthermore, in cultures of hepatocytes from male rats, the activity of the constitutive 16 alpha-testosterone hydroxylase was decreased by 1 microM dexamethasone as well as by growth hormone. The induction of 6 beta-testosterone hydroxylase by dexamethasone was suppressed by growth hormone in hepatocytes from both male and female rats, while the 7 alpha-testosterone hydroxylase activity was unaffected by culture time, hormone additions and gender. The decrease in female-specific 5 alpha-reductase activity with culture time in hepatocytes from female rats was significantly attenuated by growth hormone at 0.1 microM dexamethasone. The effects of growth hormone on testosterone hydroxylase activities in hepatocyte cultures from male and female rats are in accordance with the concept of growth hormone as a "feminization signal". The results suggest that the glucocorticoid-dependent expression of the male constitutive 16 alpha-hydroxylase requires periods of low levels of growth hormone.
Vind
C
C
Department of Biological Sciences, Royal Danish School of Pharmacy, Copenhagen.
Dich
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J
Grunnet
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D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012737:Sex Factors; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D011994:Recombinant Proteins; D003907:Dexamethasone; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; C022724:testosterone 7-alpha-hydroxylase, hamster; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase