Genetic regulation of estrogen-dependent repression of female-specific testosterone 16.alpha.-hydroxylase (I-P-45016.alpha.) in male mouse liver: murine Ripr locus

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Abstract
The genetic basis for repression if I-P-45016.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-45016.alpha. at its mRNA and activity levels. It was further found that the patterns of derepression in (129/J .times. BALB/cJ)F1 and F2 offspring indicated that the depression of I-P-45016.alpha. is inherited as an autosomal additive trait. The distribution of depression among castrated recombinant inbred strains (9 .times. A) indicated a close link of a locus repressing I-P-45016.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-45016.alpha. in livers of female mice [Noshiro, M., Lakso, M., Kawajiri, K., and 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-45016.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 locusby which repression of I-P-45016.alpha. is regulated in male mice. Treatment of castrated male BALB/cJ mice by testosterone propionate, estradiol valerate, or diethylstilbestrol repressed I-P-45016.alpha. to the levels seen in normal BALB/cJ male mice. Dihydrotestosterone, however, had little effect in repressing I-P-450116.alpha. in castrated mice. The results suggested that estrogen rather than androgen is a repressor of I-P-45016.alpha. in livers of male. The genetic and hormonal studies indicated that the Ripr locus is responsible for the estrogen-dependent repression of I-P-45016.alpha.

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