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Elevated cholesterol and dolichol synthesis in mouse pachytene spermatocytes.

1981; Elsevier BV; Volume: 256; Issue: 14 Linguagem: Inglês

10.1016/s0021-9258(19)68939-8

1083-351X

Jane E.R. Potter, C.F. Millette, Michael J. James, A.A. Kandutsch,

Hormonal and reproductive studies

Results are presented here which demonstrate that the rates of ["Clacetate incorporation into cholesterol and dolichol increased 4-to 5-fold as mouse spermatocytes matured from the preleptotene to prepuberal pachytene stages.The rate of acetate incorporation into cholesterol then decreased in late pachynema, remained low at all subsequent stages of meiosis, and was very low in mature sperm.In contrast, the rate of acetate incorporation into dolichol remained elevated in late pachytene spermatocytes and round spermatids, then decreased and remained low in mature sperm.The ratio of the rate of ["CJacetate incorporation into dolichol to the rate of incorporation into cholesterol increased during late meiotic prophase and remained high in round spermatids; this altered ratio is further evidence of independent regulation of dolichol and cholesterol synthesis in testes.It was shown previously that normal adult mouse testes incorporated acetate into dolichol at a much higher rate (1.8 to 2.4% of the rate of incorporation into cholesterol) than did testes from sterile W/ W" mice (0.02%) or X-irradiated mice (0.24%).This high rate of acetate incorporation into dolichol in adult testes is now attributed to differentiating spermatocytes, with particularly high rates being observed during pachynema.Phosphorylated derivatives of the isoprenoid lipid dolichol serve as carriers of saccharide residues during the assembly of N-glycosidically linked proteins (1-3).The biosynthetic pathway for dolichol branches from the cholesterol synthetic pathway at the level of farnesyl pyrophosphate, after the ratelimiting enzyme for cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase)' (4-6).Low concentrations of 25-hydroxycholesterol suppress HMG-CoA reductase in cultured mouse fibroblasts, sublines of NCTC 929 strain L (L-cells) and inhibit sterol synthesis, but high concentrations of inhibitor, which suppress cholesterol synthesis by 75%, are required for appreciable inhibition of dolichol synthesis (7).A similar relationship between the two