A dual role of growth hormone as a feminizing and masculinizing factor in the control of sex-specific cytochrome P-450 isozymes in rat liver.
The effects of GH on the major constitutive sex-specific forms of cytochrome P-450 (P-45015 beta and P-45016 alpha) were studied in hypophysectomized rats at the mRNA level. Time-course experiments were performed with or without simultaneous treatment with thyroxine and cortisol. Intermittent administration of GH, mimicking the male secretory pattern, caused complete masculinization of the male specific P-45016 alpha at a pretranslational level in the absence and presence of thyroxine and cortisol. When GH was administered continuously, mimicking the female secretory pattern, the female specific P-45015 beta was induced, an effect that was dramatically potentiated by simultaneous treatment with thyroxine and cortisol. A synergistic effect of thyroxine and cortisol at a pretranslational level was demonstrated, although the major potentiating effect could be attributed to thyroxine. Thus it was concluded that GH, depending on its secretory pattern is the sole masculinizing factor for cytochrome P-450, and that it is also a feminizing factor, although this activity requires the synergistic action of thyroid hormones and glucocorticoids to reach its full effect.
Mode
A
A
Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital, Sweden.
Wiersma-Larsson
E
E
Ström
A
A
Zaphiropoulos
P G
PG
Gustafsson
J A
JA
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004357:Drug Synergism; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D007016:Hypophysectomy; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D012737:Sex Factors; D013974:Thyroxine / Q000494:pharmacology
D007527:Isoenzymes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D013974:Thyroxine; D006854:Hydrocortisone