cDNA cloning, sequence, and regulation of a major female-specific and growth hormone-inducible rat liver cytochrome P-450 active in 15β-hydroxylation of steroid sulfates

P. G. Zaphiropoulos, A. Mode, A. Strom, C. Moller, C. Fernandez, J. A. Gustafsson

Research output: Contribution to journalArticle

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Abstract

cDNA clones encompassing the complete coding sequence for the female-specific rat liver microsomal 15β-hydroxylase have been isolated and sequenced. This cytochrome P-450 species (P-450 15β) has a total of 490 amino acid residues, and its deduced amino acid sequence as well as direct sequencing of the amino-terminal portion of the purified protein revealed its identity with P-450 i. P-450 15β was found to be 66% similar to the male-specific rat liver microsomal 16α-hydroxylase, P-450 16α. Furthermore, P-450 15β is 47% similar to the major phenobarbital-inducible cytochrome P-450 in rat liver, P-450 b, while its structural similarity to P-450 c, P-450 pregnenolone-16a-carbonitrile, and P-450 lauric acid ω-hydroxylase is <30%. However, the developmentally regulated cytochromes P-450 f and P-450 PB-1 both have 68% similarity to P-450 15β. It is therefore concluded that P-450 15β belongs to the same gene subfamily (P450IIC) that also includes cytochromes P-450 f, PB-1, and 16α. The plasma pattern of growth hormone (GH) is known to be a major determinant for the sex-specific expression of P-450 15β and P-450 16α. Continuous infusion of GH to hypophysectomized male rats causes an increase in P-450 15β mRNA after 6 days of treatment, while intermittent injections have no effect. On the other hand, no effect on P-450 16α mRNA is observed after continuous administration of GH, while intermittent injections cause an increase after 2 days of treatment. This relatively long period before P-450 15β and P-450 16α mRNA induction is seen might indicate that protein factors mediating GH action are involved.

Original languageEnglish (US)
Pages (from-to)4214-4217
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number12
DOIs
StatePublished - 1988

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