In @entity75 (before @entity3333 formation) of the @entity342 biosynthetic pathway induced by @entity1 CG (hCG) or LH in the Leydig cell, we initially have optimized the use of @entity6239 to obtain maximal and sustained inhibition of steroidogenesis in vivo and in vitro. @entity6239 inhibited Leydig cell steroidogenesis in vitro at a dose of 100 micrograms/ml. The minimal serum concentration of @entity6239 necessary for maximal inhibition of @entity251 in vivo was also 100 micrograms/ml (1 h after the ip injection of 20 mg @entity6239 ). However, @entity251 levels were normal 12 h later, coincident with a marked fall in the serum @entity6239 levels. The t 1/2 of the circulating @entity6239 was 5 +/- 0.7 h on the first day of treatment but was reduced to 3.0 +/- 0.4 and 2.25 +/- 0.35 h at 2 and 3 days of treatment. At the dose eliciting maximal and sustained @entity134 inhibition (60 mg/day) @entity6239 was able to prevent the @entity53 -dependent late steroidogenic lesion (after @entity3333 formation) induced by 1 microgram hCG, with no effect on the early lesion (before @entity3333 formation) caused by 10 micrograms hCG. The @entity6239 -induced in vivo accumulation of @entity165 in the inner mitochondrial membrane (by 50%) was associated with an increase in the production of @entity251 and @entity3333 by the Leydig cell when subsequently incubated in vitro. Similar increases in the steroidogenic capacity were observed after initial exposure of Leydig cells to @entity6239 in vitro, even after acid wash to remove the surface-bound endogenous LH. The steroidogenic @entity165 was also increased in desensitized Leydig cells (by 50-70%); however, the conversion of @entity165 to @entity3333 was substantially blocked in animals with the early lesion. Our findings define the requirement of increasing high levels of @entity6239 to inhibit @entity165 metabolism and provide a dose schedule suitable for studies on @entity165 availability and inhibition of steroidogenesis in the @entity35 . These results support our proposal that the early lesion observed in desensitized Leydig cells is due to inhibition of the side-chain cleavage activity rather than to a decrease in the amount of metabolically available @entity165 .

Mitochondrial XXXX availability during gonadotropin-induced Leydig cell desensitization.

@entity1 :: ('9606', 'Species') :: ['human'] @entity251 :: ('MESH:D013739', 'Chemical') :: ['testosterone'] @entity75 :: ('MESH:D001927', 'Disease') :: ['order to define the early lesion'] @entity3333 :: ('MESH:D011284', 'Chemical') :: ['pregnenolone'] @entity6239 :: ('MESH:D000616', 'Chemical') :: ['Aminoglutethimide', 'aminoglutethimide'] @entity53 :: ('MESH:D004958', 'Chemical') :: ['estradiol'] @entity134 :: ('CHEBI:35341', 'Chemical') :: ['steroid'] @entity342 :: ('CHEBI:50113', 'Chemical') :: ['androgen'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol']
@entity165 :: (MESH:D002784,Chemical) :: ['cholesterol']
