OESTROGEN INDUCED LEYDIG CELL REFRACTORINESS TO GONADOTROPHIN STIMULATION

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Abstract
In vivo administration of estradiol to male rats modifies plasma LH [lutropin], FSH [follitropin] and testosterone levels, c[cyclic]AMP and testosterone production and DNA synthesis in isolated interstitial cells. Injection of estradiol benzoate (E2B) i.m. at the dose of 1 or 100 .mu.g/day for 6 days induced a 5- and 10-fold decrease in plasma testosterone, respectively, and a 2-fold decrease in plasma LH and FSH. Plasma testosterone was already significantly decreased 2 h after the E2B injection at which point the plasma LH and FSH levels were not yet significantly decreased. In vivo steroidogenic responsiveness to hCG [human chorionic gonadotropin] evaluated by plasma and testicular contents was already significantly lower than that of controls 2 h following estradiol administration. Thereafter response to hCG progressively decreased during the 6 days of 1 or 100 .mu.g estradiol treatment, reaching 30 and 10%, respectively, of that of controls on the last day. The testicular cAMP content 2 h after hCG injection was significantly higher in estradiol treated animals than in controls after 24 h. The number of hCG binding sites in isolated Leydig cells decreased to approximately 50% of that of controls on days 3 to 6 following E2B treatment. In vitro testosterone production by isolated interstitial cells, either under basal conditions or under stimulation by hCG or N6O2 dibutyryl-cAMP (DbcAMP), was lowered as early as 2 h following E2B injection. From 1 to 6 days following E2B administration, testosterone secretion, in response to both stimuli, was approximately 4 times lower than that of the control animals. By the 2nd day of estrogen treatment, basal and hCG induced in vitro cAMP production by interstitial cells was significantly higher than controls despite a significant decrease in the number of binding sites. The incorporation of thymidine into interstitial cells DNA were decreased following 2 days of estrogen administration. The conversion of pregnenolone to testosterone was unchanged. These inhibitory effects of estradiol were not overcome by simultaneous hCG administration. The rapid inhibitory action of estradiol on interstitial cell function, steroidogenesis, and DNA synthesis, apparently occurs at the testicular level. Changes observed in gonadotropin receptors sites or in plasma LH levels may have a long term effect on the steroidogenic refractoriness to hCG. This refractoriness is primarily related to an abnormality of some step of steroidogenesis beyond cAMP formation.

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