Séguin C, Bélanger A, Labrie F, Hansel W
Endocrinology. 1982 Feb;110(2):524-30. doi: 10.1210/endo-110-2-524.
Is it well known that LHRH agonists can inhibit testicular functions by gonadal desensitization secondary to endogenous LH release and that a direct action at the gonadal level has also been demonstrated. Since an excess of anti-LH serum can be used, as an alternative to hypophysectomy, to neutralize the influence of endogenous LH release, the relative importance of the testis and pituitary gland in the inhibitory effect of a LHRH agonist, [D-Ser-(TBU)6,des-Gly-NH210]LHRH ethylamide (Buserelin), was studied on gonadal gonadotropin receptors in intact adult male rats treated with equine anti-LH or normal horse serum (NHS). A single administration of increasing doses (1-100 ng) of Buserelin leads to a progressive inhibition of testicular LH and PRL receptor levels by 70% and 40%, respectively, in animals injected with NHS. Treatment with the anti-LH serum completely prevents this inhibitory effect of a single dose of the LHRH agonist. After two successive injections of Buserelin in NHS-treated animals, testicular LH receptors are reduced by 70% and 80% with the 100- and 500-ng doses, respectively, while testicular PRL receptors are inhibited by 40-60%. In animals treated with the anti-LH serum, the inhibition of testicular LH receptors is reduced by only 18% (100 ng Buserelin) and 55% (500 ng Buserelin), while the inhibitory effect on PRL receptors is abolished. The present data show that endogenous LH release induced by a single injection of a LHRH agonist plays an essential role in the loss of testicular LH receptors measured 2 days later. Moreover, upon repeated injection of the LHRH agonist, neutralization of endogenous LH release by an anti-LH serum markedly reduces the inhibitory effect of the LHRH agonist on LH receptors, while it completely prevents the effect on PRL receptors, suggesting that the inhibitory effect of the LHRH agonist in the male rat is predominantly due to endogenous LH release rather than to a direct action of the peptide at the testicular level.
众所周知，促黄体生成素释放激素（LHRH）激动剂可通过内源性促黄体生成素（LH）释放继发的性腺脱敏作用抑制睾丸功能，并且在性腺水平的直接作用也已得到证实。由于过量的抗LH血清可用于替代垂体切除术来中和内源性LH释放的影响，因此研究了在完整成年雄性大鼠中，LHRH激动剂[D-丝氨酸-（叔丁基）6，去甘氨酸-NH210]LHRH乙酰胺（布舍瑞林）对性腺促性腺激素受体的抑制作用中，睾丸和垂体的相对重要性，这些大鼠用马抗LH或正常马血清（NHS）处理。在注射NHS的动物中，单次给予递增剂量（1-100 ng）的布舍瑞林分别导致睾丸LH和催乳素（PRL）受体水平逐渐抑制70%和40%。用抗LH血清治疗可完全阻止单剂量LHRH激动剂的这种抑制作用。在NHS处理的动物中连续两次注射布舍瑞林后，100 ng和500 ng剂量的睾丸LH受体分别减少70%和80%，而睾丸PRL受体被抑制40%-60%。在用抗LH血清处理的动物中，睾丸LH受体的抑制仅减少18%（100 ng布舍瑞林）和55%（500 ng布舍瑞林），而对PRL受体的抑制作用则被消除。目前的数据表明，单次注射LHRH激动剂诱导的内源性LH释放在2天后测量的睾丸LH受体丧失中起重要作用。此外，重复注射LHRH激动剂时，抗LH血清对内源性LH释放的中和作用显著降低了LHRH激动剂对LH受体的抑制作用，而它完全阻止了对PRL受体的作用，这表明LHRH激动剂在雄性大鼠中的抑制作用主要归因于内源性LH释放，而不是该肽在睾丸水平的直接作用。
