Huhtaniemi I T, Stewart J M, Channabasavaiah K, Fraser H M, Clayton R N
Mol Cell Endocrinol. 1984 Feb;34(2):127-35. doi: 10.1016/0303-7207(84)90064-9.
Gonadotropin secretion of adult male rats was inhibited by one-week treatment with a GnRH antagonist analogue (N-acetyl-Ala1,D-p-Cl-Phe2,D-Trp3,6-GnRH, Ant.) or a GnRH antiserum (A/S). Since Ant. but not A/S binds to GnRH receptors (R), it was expected that comparison of the two treatment regimes would elucidate a physiological role for testicular GnRH-R. Furthermore, the effect of combined gonadotropin and prolactin deficiency was studied in rats treated with Ant. and bromocriptine (BR). Available pituitary GnRH-R were decreased by both Ant. and A/S (P less than 0.01), but not by BR. Testicular content of free GnRH-R was decreased by Ant. by 70-80% (P less than 0.01), probably owing to occupancy, but A/S and BR had no effect on these binding sites. Serum LH and FSH fell by about 75% with Ant. and A/S treatments (P less than 0.01), and Prl by 90% with BR (P less than 0.01). Intratesticular testosterone (T) decreased significantly with Ant. and A/S treatment (P less than 0.01-0.05), but was unaffected by BR. Only Ant. and BR treatments together, but neither alone, were able to suppress Leydig cell capacity to produce T in vitro. Relative blockade of C21 steroid side-chain cleavage by Ant. and A/S was suggested by elevated progesterone (P) and/or P/T ratios in the serum and testis tissues. Ant. and A/S had no effect on testicular LH and FSH-R, but both decreased testicular Prl-R by about 50% (P less than 0.01-0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
用促性腺激素释放激素(GnRH)拮抗剂类似物(N-乙酰基-Ala1,D-对氯苯丙氨酸2,D-色氨酸3,6-GnRH,Ant.)或GnRH抗血清(A/S)对成年雄性大鼠进行为期一周的治疗,可抑制其促性腺激素分泌。由于Ant.能与GnRH受体(R)结合而A/S不能,因此预期比较这两种治疗方案将阐明睾丸GnRH-R的生理作用。此外,还研究了用Ant.和溴隐亭(BR)治疗的大鼠中促性腺激素和催乳素联合缺乏的影响。Ant.和A/S均可使垂体中可用的GnRH-R减少(P<0.01),但BR无此作用。Ant.使睾丸中游离GnRH-R的含量降低70-80%(P<0.01),这可能是由于受体被占据,而A/S和BR对这些结合位点无影响。Ant.和A/S治疗使血清促黄体生成素(LH)和促卵泡生成素(FSH)下降约75%(P<0.01),BR使催乳素(Prl)下降90%(P<0.01)。Ant.和A/S治疗使睾丸内睾酮(T)显著降低(P<0.01-0.05),但BR对其无影响。只有Ant.和BR联合治疗能够抑制睾丸间质细胞体外产生T的能力,单独使用二者均无此作用。血清和睾丸组织中孕酮(P)升高和/或P/T比值升高提示Ant.和A/S对C21甾体侧链裂解有相对阻断作用。Ant.和A/S对睾丸LH和FSH-R无影响,但二者均使睾丸Prl-R降低约50%(P<0.01-0.05)。(摘要截短于250字)