Genotype at the P450sccLocus Determines Differences in the Amount of P450sccProtein and Maximal Testosterone Production in Mouse Leydig Cells

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Abstract
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 33H 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 < 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. These results demonstrate that the genotype at the P450scc locus, which were previously mapped to mouse chromosome 9, determined the amount of Leydig cell P450scc protein and that the amount of p450scc protein is an important determinant of Leydig cell capacity for testosterone production in these strains.

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