Direct inhibition of testicular steroidogenesis and gonadotrophin receptor levels by [(imBzl)-D-His6, Pro9-NEt]GnRH and [D-Trp6, Pro9-NEt]GnRH, potent agonists of GnRH

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Abstract
The effects of [(imBzl)-D-His6, Pro9-NEt]GnRH [gonadotropin releasing hormone] and [D-Trp6, Pro9-NEt]GnRH on testicular function in rats was evaluated. In adult rats the administration of 0.01, 0.1 or 10 .mu.g of either agonist induced rapid increases in serum LH [lutropin], FSH and testosterone (T) levels which started to decline within several hours. Both agonists caused a decrease in testicular LH and FSH receptor concentrations. The testicular FSH receptor concentration started to decline earlier than the LH receptor concentration, but both reached their lowest levels by day 2 after the administration of the agonists. The recovery of FSH receptor content was slower than that of LH. The extrapituitary effects of the 2 agonists were investigated in immature hypophysectomized animals. Administration of hCG [human chorionic gonadotropin] (5 IU daily) to hypophysectomized rats for 5 days caused an increase in serum T levels. Concomitant administration of either of the agonists (10 .mu.g) inhibited the steroidogenic action of hCG. Administration of the agonists alone caused a reduction in testicular LH receptor concentration in hypophysectomized rats. Treatment of the hypophysectomized rats for 0-4 days suggested that the direct antitesticular action of the agonists requires 1-2 days to become evident.

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