Genetic regulation of estrogen-dependent repression of female-specific testosterone 16 alpha-hydroxylase (I-P-450(16 alpha) in male mouse liver: murine Ripr locus.
The genetic basis for repression of I-P-450(16 alpha) in livers of male mice was examined in 129/J and BALB/cJ mice. Castration of adult male BALB/cJ but not 129/J mice resulted in derepression of I-P-450(16 alpha) at its mRNA and activity levels. It was further found that the patterns of derepression in (129/J x BALB/cJ) F1 and F2 offspring indicated that the derepression of I-P-450(16 alpha) is inherited as an autosomal additive trait. The distribution of derepression among castrated recombinant inbred strains (9 X A) indicated a close link of a locus repressing I-P-450(16 alpha) in male mice to the Rip locus on chromosome 7. Rip was previously defined as a locus that regulates specific expression of I-P-450(16 alpha) in livers of female mice [Noshiro, M., Lakso, M., Kawajiri, K., & Negishi, M. (1988) Biochemistry (preceding paper in this issue)]. Other tested inbred mice (A/HeJ, C57BL/6J, C3H/HeJ, and DBA/2J) showed the derepression of I-P-450(16 alpha) by castration, such as BALB/cJ. We propose Ripr (repression of an action of Rip locus in male mice) as the name of the locus by which repression of I-P-450(16 alpha) is regulated in male mice. Treatment of castrated male BALB/cJ mice by testosterone propionate, estradiol valerate, or diethylstilbestrol repressed I-P-450(16 alpha) to the levels seen in normal BALB/cJ male mice. Dihydrotestosterone, however, had little effect in repressing I-P-450(16 alpha) in castrated mice. The results suggested that estrogen rather than androgen is a repressor of I-P-450(16 alpha) in livers of male mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Noshiro
M
M
Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Negishi
M
M
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D004794:Enzyme Repression; D005260:Female; D005786:Gene Expression Regulation; D005796:Genes; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000201:enzymology; D009919:Orchiectomy; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D012737:Sex Factors; D013045:Species Specificity; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; C022724:testosterone 7-alpha-hydroxylase, hamster