R1881 regulation of steroidogenesis in cultured testicular cells.
The influence of a synthetic androgen R1881 upon hCG stimulated steroidogenesis in cultured rat testicular cells was investigated. Testicular cells were cultured for 8 days in medium alone and thereafter reincubated for 48 h with appropriate treatments before the collection of media for steroid RIA. Addition of R1881 (10(-6) M) resulted in an overall decrease of hCG (0.3-10 ng/ml) stimulated pregnenolone and progesterone production by cultured cells. The conversion of exogenous steroids of the delta 4 pathway (progesterone,17 alpha-OH-P and delta 4-A) was also studied in cultures supplemented with cyanoketone (10(-5) M) and/or spironolactone (10(-5) M) to prevent endogenous testosterone production. R1881 inhibited progesterone and 17 alpha-OH-P conversion to testosterone (T) and was ineffective when delta 4-A served as precursor for T biosynthesis. The inhibitory effect of R1881 upon Testosterone production was prevented by concomitant treatment with CPA. These observations suggest that R1881 decreases the hCG stimulated testosterone production via inhibition of CSCCE,3 beta-HSD,C17-20 Lyase and likely 17 alpha-Hydroxylase, whereas no effect on 17 beta-HSD could be observed.
Fanjul
L F
LF
Departamento de Bioquímica y Biología Molecular, Universidad de La Laguna, Las Palmas de Gran Canaria, Spain.
Estévez
F
F
Déniz
A
A
Marrero
I
I
Benítez
L
L
Quintana
J
J
González
J
J
Centol
I
I
Ruiz de Galarreta
C M
CM
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000446:Aldehyde-Lyases / Q000037:antagonists & inhibitors; D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors; D006063:Chorionic Gonadotropin / Q000502:physiology; D003534:Cyproterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017373:Cyproterone Acetate; D065607:Cytochrome P-450 Enzyme Inhibitors; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D015741:Metribolone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D013739:Testosterone / Q000096:biosynthesis*; D045165:Testosterone Congeners / Q000494:pharmacology*
D000726:Androgen Antagonists; D006063:Chorionic Gonadotropin; D065607:Cytochrome P-450 Enzyme Inhibitors; D045165:Testosterone Congeners; D015741:Metribolone; D013739:Testosterone; D017373:Cyproterone Acetate; D003534:Cyproterone; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; C022445:progesterone 17-alpha-hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D000446:Aldehyde-Lyases