Initiation of steroidogenesis precedes expression of cholesterologenic enzymes in the fetal mouse testes.
Sexual differentiation is a carefully regulated process that ultimately results in a development of the male or female phenotype. Proper development of the male phenotype is dependent upon the action of testosterone and anti-mullerian hormone. Leydig cells start to produce testosterone around day 12.5 in the fetal mouse testis, and continue to produce high levels of this hormone throughout gestation. In the present study, we examined whether expression of lanosterol 14alpha-demethylase (cyp51) and cytochrome P450 NADPH reductase, both involved in the cholesterol production, occurs simultaneously with proteins required for the production of steroid hormones. Immunocytochemical staining with the antibodies against cyp51, cytochrome P450 NADPH reductase, steroidogenic acute regulatory protein (StAR) and 3beta-hydroxysteroid dehydrogenase I (3beta-HSD I) was used to determine the ontogeny of expression of these four proteins. As expected, 3beta-HSD I and StAR proteins were detected on day 12.5 p.c., while expression of cyp51 and NADPH cytochrome P450 reductase appeared 1 day later, on day 13.5. Thereafter, the expression of all four proteins remained strong throughout gestation. Results of this study suggest that initial steps of steroid hormone production in murine Leydig cells are mostly dependent on exogenously derived cholesterol, while from day 13.5 onwards, mouse Leydig cells are able to synthesize cholesterol and are therefore not dependent on exogenous cholesterol resources.
Büdefeld
T
T
Center for Animal Genomics, Veterinary Faculty, University of Ljubljana, Gerbiceva 60, SI-1000 Ljubljana, Slovenia.
Jezek
D
D
Rozman
D
D
Majdic
G
G
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D005325:Fetal Organ Maturity / Q000502:physiology; D005333:Fetus / Q000196:embryology; D005865:Gestational Age; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis; D007985:Leydig Cells / Q000502:physiology; D008297:Male; D051379:Mice; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011247:Pregnancy; D058886:Sterol 14-Demethylase; D000098682:Steroidogenic Acute Regulatory Protein
D012739:Gonadal Steroid Hormones; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D015096:3-Hydroxysteroid Dehydrogenases; C548415:Cyp51 protein, mouse; D058886:Sterol 14-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase