Genotype at the P450_sccLocus Determines Differences in the Amount of P450_sccProtein and Maximal Testosterone Production in Mouse Leydig Cells

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 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)

Sertoli cells control peritubular myoid cell fate and support adult Leydig cell development in the prepubertal testis

“…This is consistent with the increase in Cyp11a1 transcript levels seen after SC ablation, as the cholesterol side-chain cleavage enzyme CYP11A1 catalyses one of the rate-limiting steps in testosterone synthesis (Nolan and Payne, 1990). Circulating testosterone levels are normally part of a homeostatic control mechanism regulating LH secretion and LC activity, but LH levels were not significantly affected following SC ablation on pnd2.…”

Multiple forms of mouse 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase and differential expression in gonads, adrenal glands, liver, and kidneys of both sexes.

“…3) placental 3,3HSD (11). The specificity of this antiserum for mouse Leydig cells and adrenal glands was validated previously (24). Fig.…”

Expression of steroidogenic enzymes during equine testicular development

“…In addition, CYP17 mRNA increased from prepubertal to adult testis, which is consistent with our immunohistochemical observations. LH is the main regulator of testosterone biosynthesis by Leydig cells, and P450c17 activity has been detected in Leydig cells of various species such as the rat (O'Shaughnessy & Murphy 1991), mouse (Nolan & Payne 1990), human (Hammar & Petersson 1986), goat (Weng et al 2005), and boar (Raeside et al 2006). In addition, CYP17 and HSD3B1 expression has been reported in Leydig cells and other testicular cells, such as Sertoli cells and spermatogenic cells in several species including the monkey (Liang et al 1998), American black bear (Tsubota et al 1997), Japanese black bear (Okano et al 2003), Hokkaido brown bear (Tsubota et al 1993), and Japanese raccoon dog (Qiang et al 2003).…”