cDNA cloning, sequence, and regulation of a major female-specific and growth hormone-inducible rat liver cytochrome P-450 active in 15 beta-hydroxylation of steroid sulfates.
cDNA clones encompassing the complete coding sequence for the female-specific rat liver microsomal 15 beta-hydroxylase have been isolated and sequenced. This cytochrome P-450 species (P-450 15 beta) 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 15 beta was found to be 66% similar to the male-specific rat liver microsomal 16 alpha-hydroxylase, P-450 16 alpha. Furthermore, P-450 15 beta 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 omega-hydroxylase is less than 30%. However, the developmentally regulated cytochromes P-450 f and P-450 PB-1 both have 68% similarity to P-450 15 beta. It is therefore concluded that P-450 15 beta belongs to the same gene subfamily (P450IIC) that also includes cytochromes P-450 f, PB-1, and 16 alpha. The plasma pattern of growth hormone (GH) is known to be a major determinant for the sex-specific expression of P-450 15 beta and P-450 16 alpha. Continuous infusion of GH to hypophysectomized male rats causes an increase in P-450 15 beta mRNA after 6 days of treatment, while intermittent injections have no effect. On the other hand, no effect on P-450 16 alpha 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 15 beta and P-450 16 alpha mRNA induction is seen might indicate that protein factors mediating GH action are involved.
Zaphiropoulos
P G
PG
Department of Medical Nutrition, Huddinge University Hospital, Sweden.
Mode
A
A
Ström
A
A
Möller
C
C
Fernandez
C
C
Gustafsson
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D004262:DNA Restriction Enzymes; D004790:Enzyme Induction; D005260:Female; D005796:Genes; D013006:Growth Hormone / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013250:Steroid Hydroxylases / Q000096:biosynthesis / Q000235:genetics*
D013006:Growth Hormone; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C034694:steroid 15-beta-hydroxylase; D004262:DNA Restriction Enzymes