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Female-predominant expression of testosterone 16 alpha-hydroxylase ("I"-P-450(16)alpha) and its repression in strain 129/J.

Abstract：

:Using specific testosterone 16 alpha-hydroxylase activity as the basis for selection of fractions during purification, the cytochrome P-450 ("I"-P-450(16)alpha) has been isolated from livers of phenobarbital-treated 129/J female mice [K. Devore, N. Harada, and M. Negishi (1985) Biochemistry, 24, 5632-5637]. An antibody elicited in rabbits to "I"-P-450(16)alpha was used to determine the amount of hepatic microsomal 16 alpha-hydroxylase activity due to "I"-P-450(16)alpha in untreated females and males of the two mouse strains, 129/J and BALB/cJ. The activities inhibited were 0.03 and 0.3 nmol/min/mg protein in the 129/J and BALB/cJ females, respectively. No significant level of "I"-P-450(16)alpha-dependent activity was detected in the microsomes from males of either mouse strain. Immunoblotting of microsomal proteins with the antibody to "I"-P-450(16)alpha revealed approximately a 10-fold greater amount of a 54-kDa protein in the microsomes from BALB/cJ than from 129/J females (0.03 and 0.26 pmol/micrograms protein, respectively). A cDNA clone (R17) for phenobarbital-inducible rat cytochrome P-450 selected "I"-P-450(16)alpha mRNA of mice, indicating a high degree of homology between the mRNAs of mouse "I"-P-450(16)alpha and phenobarbital-inducible rat cytochrome P-450s. Northern and dot hybridization of total mouse liver poly(A)+ RNA with the R17 cDNA probe indicated that the specific content of the hybridizable mRNA was more than 10 times higher in BALB/cJ females than in males, and that the mRNA level in female 129/J mice was very similar to that of 129/J and BALB/cJ males. The repression of "I"-P-450(16)alpha in 129/J females was inherited as an autosomal recessive trait in 129/J and BALB/cJ pairs as indicated by the levels of mRNA in female F1 offspring and the "I"-P-450(16)alpha-dependent hydroxylase activity. Female and male mice of eight more inbred strains (AKR/J, DBA/2J, C57BL/6J, C3H/HeJ, NZB/J, A/J, CBA/CaJ, and P/J) were tested for levels of mRNA. The results showed that the levels of mRNA were always 5- to 10-fold greater in the females than in the corresponding males, although there was some variation in the mRNA content in the males from the different strains. 129/J females appear to be a genetic variant where the female-predominant expression of the mRNA is repressed.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

Noshiro M,Serabjit-Singh CJ,Bend JR,Negishi M

doi

10.1016/0003-9861(86)90655-7

subject

Has Abstract

pub_date

1986-02-01 00:00:00

pages

857-64

issue

eissn

0003-9861

issn

1096-0384

pii

0003-9861(86)90655-7

journal_volume

244

pub_type

杂志文章

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Female-predominant expression of testosterone 16 alpha-hydroxylase ("I"-P-450(16)alpha) and its repression in strain 129/J.