hCG投与に対するラット睾丸の自己調節機構

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Occupancy of luteinizing hormone (LH) /human chorionic gonadotropin (hCG) receptors in testes by LH or hCG is followed by stimulation of 3' : 5'-cyclic AMP (cAMP) production and testosterone synthesis. However, recently a sustained loss of testicular LH/hCG receptors after systemic administration of LH or hCG has been observed. Therefore we studied the functional relations between negative regulation of LH/hCG receptors and desensitization of cAMP and steroidogenic responses in the testes of rats treated with exogenous gonadotropin. Adult male rats (200-250gr) were orchiectomized everyday for a week after an intraperitoneal injection of 20 or 200IU of hCG. The LH/hCG receptors in the testes were determined by incubating 50mg testis slice with 125I-hCG in the absence or presence of hCG. The effects of hCG pretreatment on cAMP and testosterone responses to the in vitro addition of hCG were also investigated. The specific binding of 125I-hCG to LH/hCG receptors dropped rapidly to undetectable level at 24hr after 2001U hCG, remained undetectable for 3 days and began to recover at 4 days. After 20IU hCG, the specific binding of 125I-hCG did not decline up to 24hr, then fell to 44-68% at 2 days, and began to recover at 3 or 4 days. Scatchard analysis showed that the reduced binding of 125 125I-hCG was due to a reduction in the number of receptor sites without any change in affinity. These findings demonstrate that the hCG-induced change in testicular LH/hCG receptor is characterized by a progressive and dose-related loss of the receptors. Pretreatment with both 20 and 2001U of hCG caused a marked increase in basal testosterone production in vitro at 24hr, but the testosterone responses to the addition of hCG in vitro were minimal at 24hr and recovered at 2 and 3 days after 20 and 200IU of hCG, respectively. Thereafter the testosterone responses increased 3 to 6 folds above those of intact rat testis. hCG-induced cAMP production in vitro was inhibited markedly at 24hr after 20 and 200IU hCG injection. Then the cAMP responses to hCG recovered gradually and were the same as those of the control after 4 days when testosterone responses were still high. This marked disparity between the recoveries of cAMP and testosterone responses after hCG treatment suggests that the testosterone synthetic enzymes located beyond cAMP formation are activated as a result of direct and delayed hCG action. Another interesting point is that both testosterone and cAMP responses to hCG at 24hr after 20IU hCG were reduced to 11-31% of the control without a reduction in LH/ hCG receptors. This finding indicates that the initial block in steroidogenic responses to a small amount of hCG is not an immediate consequence of receptor loss, but must be located in the steps between LH/hCG receptor and cAMP formation. These studies have shown that the responses of target cells after hCG injection undergo a series of changes; the desensitization and recovery of testis function. The earliest change seems to be rapid loss of cAMP response to hCG and then the dose-related loss of the free hCG receptors occurs. The elevated testosterone response to hCG is the late effect of hCG.

hCG投与に対するラット睾丸の自己調節機構

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