[The role of gonadotropins, cyclic AMP, 22-R-OH-cholesterol and cofactors in regulating endocrine functions of the Leydig cells in rats. III. Mechanisms responsible for "desensitization" of the Leydig cells of rats caused by high doses of hCG].

Two groups of rats (a control group and the group examined) were administered intraperitoneally supraphysiological doses of hCG in order to induce a "down regulation" effect on the level of receptors LH and to achieve the desensibilization of Leydig cells. The authors tried to find out at which stage of sequence of changes from receptor stimulation to hormone production there appears a state of cellular resistance to further stimulation. Sections of the nucleus were incubated with various substances influencing steridogenesis (LH, hCG, dbcAMP, 22-R-OH-cholesterol, NAD + NADP + G-6-P + G-6-PDH). An index of the influence of the above substances on the synthesis of androgens were amounts of pregnenolon as the first and testosterone as the final stage of hormonal changes marked radioimmunologically in nucleus homogenates and incubating media. It was shown that the resistance of Leydig cells to further stimulation in the group of animals that were given high doses of hCG is the result of enzymatic blocks in testosterone synthesis. The first block is "late" block of 17 alpha-hydroxylase and 17-20 desmolase, disturbing transforming of 21-carbon steriods into 19-carbon androgens. When the dose of hCG increases, there appears the second block, the so called "early" block, disturbing mitochondrial synthesis of pregnenolon. It was found that exogenic cofactors are in a position, at least partially, to restore the activity of blocked enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)