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Expression of cytochrome P-450(17) alpha, 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase, and steroid 5 alpha-reductase in rat H540 Leydig tumor cells.
- Source :
-
Molecular and cellular endocrinology [Mol Cell Endocrinol] 1990 Dec 21; Vol. 74 (3), pp. R11-7. - Publication Year :
- 1990
-
Abstract
- The rat H540 Leydig tumor cell is established as a model for acute lutropin action on the initial step of steroidogenesis, namely the conversion of cholesterol to pregnenolone. Herein, we demonstrate that H540 cells express high levels of three steroid-metabolizing enzymes which are involved in the further processing of pregnenolone in the endoplasmic reticulum of the steroidogenic cell. In particular, in addition to expressing 17 alpha-hydroxylase cytochrome P-450 (P-450(17) alpha) and 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase (3 beta-HSD), H540 cells also showed high levels of steroid 5 alpha-reductase mRNA and activity. The H540 cells therefore exhibit similarity to Leydig cells from sexually immature animals which also demonstrate high 5 alpha-reductase activity. Thus, after 3 beta-HSD-catalyzed formation from pregnenolone, progesterone was efficiently converted to 5 alpha-pregnan-3,20-dione (5 alpha-dihydroprogesterone) and subsequent metabolism to the corresponding 17 alpha-hydroxylated derivative and 5 alpha-androstan-3,17-dione in a reaction catalyzed by P-450(17) alpha. H540 cells have apparently very low 17-ketosteroid reductase activity and, therefore, a principal end-product of the steroidogenic pathway in these cells was 5 alpha-androstan-3,17-dione. H540 cells maintained in primary culture under serum-free conditions accumulated demonstrable levels of mRNA species for P-540 17 alpha (1.7 kb), 3 beta-HSD (1.6 kb) and 5 alpha-reductase (2.7 kb). This finding suggests that the H540 tumor cell model will not only be of utility in the study of acute lutropin action but also in the elucidation of mechanisms involved in the regulation of expression of various families of microsomal steroid-metabolizing enzymes.
- Subjects :
- 3-Oxo-5-alpha-Steroid 4-Dehydrogenase genetics
5-alpha-Dihydroprogesterone
Animals
Cytochrome P-450 Enzyme System genetics
DNA Probes
Gene Expression Regulation
Leydig Cells
Luteinizing Hormone metabolism
Male
Multienzyme Complexes genetics
Pregnanediones metabolism
Progesterone Reductase genetics
RNA, Messenger analysis
Rats
Rats, Inbred F344
Steroid Isomerases genetics
Tumor Cells, Cultured enzymology
3-Oxo-5-alpha-Steroid 4-Dehydrogenase biosynthesis
Cytochrome P-450 Enzyme System biosynthesis
Multienzyme Complexes metabolism
Progesterone Reductase metabolism
RNA, Messenger metabolism
Steroid Isomerases biosynthesis
Steroid Isomerases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0303-7207
- Volume :
- 74
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular and cellular endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 2095353
- Full Text :
- https://doi.org/10.1016/0303-7207(90)90231-v