Growth hormone regulation of hepatic cytochrome P450 expression in the rat.
GH by means of its sexually differentiated secretory pattern is the predominant regulator of the expression of cytochrome P450 enzymes responsible for a sexual dimorphism of hepatic steroid metabolism. Other hormones, such as gonadal, thyroid and glucocorticoid hormones, as well as insulin appear to modulate the sexually differentiated expression of these enzymes. The major constitutively expressed sex specific forms of P450, belonging to the P4502C-subfamily, have been shown to be regulated by GH at the level of transcription. However, the GH postreceptor events leading to increased or decreased transcriptional activity are essentially unknown. Neither is the functional role of the soluble GH binding protein yet resolved. On-going protein synthesis is a prerequisite for GH transcriptional activation of the female specific P4502C12 but not for all GH effects in the hepatocyte. With regard to signalling mechanisms PKC activity appears to be permissive for the GH induction of P4502C12 but some as yet unidentified factor/kinase(s) may also be activated. The transcriptional control exerted on the rat P4502C-gene subfamily by the pattern of GH secretion offers a versatile tool to elucidate the molecular mechanisms of GH regulation of cytochrome P450 expression.
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Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital, Sweden.
Tollet
P
P
Ström
A
A
Legraverend
C
C
Liddle
C
C
Gustafsson
J A
JA
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004252:DNA Mutational Analysis; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D013006:Growth Hormone / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011986:Receptors, Somatotropin / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D012727:Sex Characteristics; D015398:Signal Transduction
D000728:Androgens; D004967:Estrogens; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System