Genotype at the P450scc locus determines differences in the amount of P450scc protein and maximal testosterone production in mouse Leydig cells.
A genetic difference in maximal testosterone production in Leydig cells relates to differences in the genotype at the P450scc locus. The genetic relationship between the P450scc gene, the amount of Leydig cell P450scc protein, and maximal testosterone production was determined in the F2 generation of mice derived from SWR/J mice (SWR), a high Leydig cell testosterone-producing strain, and from C3H/HeJ (C3H), a low Leydig cell testosterone-producing strain. A restriction fragment length polymorphism was identified in the P450scc gene between SWR and C3H mice. This restriction fragment length polymorphism was used to identify F2 mice homozygous for the SWR or the C3H alleles of the P450scc gene. The two types of homozygous mice were compared with regard to maximal testosterone production and the amounts of P450scc, P45017 alpha, and 3 beta-hydroxysteroid dehydrogenase isomerase (3 beta HSD) proteins. Maximal testosterone production, amounts of P450scc and 3 beta HSD were significantly greater in the SWR than in the C3H progenitor mice. In the F2 mice, homozygous for either the SWR or the C3H allele of P450scc, the differences in maximal testosterone production and the amount of P450scc protein were comparable to the differences in the two progenitor strains. A significant correlation (r = 0.75; P less than 0.01) was found between the amount of P450scc protein and maximal testosterone production. No differences in the amounts of P45017 alpha or 3 beta HSD were observed in the F2 males.(ABSTRACT TRUNCATED AT 250 WORDS)
Nolan
C J
CJ
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor 48109-0278.
Payne
A H
AH
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000483:Alleles; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D005838:Genotype; D006720:Homozygote; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D012150:Polymorphism, Restriction Fragment Length; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*
D013739:Testosterone; D000242:Cyclic AMP; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme