Lanosterol 14 alpha-demethylase (CYP51), NADPH-cytochrome P450 reductase and squalene synthase in spermatogenesis: late spermatids of the rat expressproteins needed to synthesize follicular fluid meiosis activating sterol

Citation
C. Majdic et al., Lanosterol 14 alpha-demethylase (CYP51), NADPH-cytochrome P450 reductase and squalene synthase in spermatogenesis: late spermatids of the rat expressproteins needed to synthesize follicular fluid meiosis activating sterol, J ENDOCR, 166(2), 2000, pp. 463-474
Citations number
39
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
JOURNAL OF ENDOCRINOLOGY
ISSN journal
00220795 → ACNP
Volume
166
Issue
2
Year of publication
2000
Pages
463 - 474
Database
ISI
SICI code
0022-0795(200008)166:2<463:L1A(NP>2.0.ZU;2-4
Abstract
Lanosterol 14 alpha-demethylase (CYP51) is a cytochrome P450 enzyme involve d primarily in cholesterol biosynthesis. CYP51 in the presence of NADPH-cyt ochrome P450 reductase converts lanosterol to follicular fluid meiosis acti vating sterol (FF-MAS), an intermediate of cholesterol biosynthesis which a ccumulates in gonads and has an additional function as oocyte meiosis-activ ating substance. This work shows for the first time that cholesterogenic en zymes are highly expressed only in distinct stages of spermatogenesis. CYP5 1, NADPH-P450 reductase (the electron transferring enzyme needed for CYP51 activity) and squalene synthase (an enzyme preceding CYP51 in the pathway) proteins have been studied. CYP51 was detected in step 3-19 spermatids, wit h large amounts in the cytoplasm/residual bodies of step 19 spermatids, whe re P450 reductase was also observed. Squalene synthase was immunodetected i n step 2-15 spermatids of the rat, indicating that squalene synthase and CY P51 proteins are not equally expressed in same stages of spermatogenesis. D iscordant expression of cholesterogenic genes may be a more general mechani sm leading to transient accumulation of pathway intermediates in spermatoge nesis. This study provides the first evidence that step 19 spermatids and r esidual bodies of the rat testis have the capacity to produce MAS sterols i n situ.