Painson J C, Tannenbaum G S
Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
Endocrinology. 1991 Jun;128(6):2858-66. doi: 10.1210/endo-128-6-2858.
A striking sexual dimorphism exists in the pattern of GH secretion and rate of somatic growth; however, the mechanism(s) mediating this sex difference is unknown. To elucidate the physiological roles of the hypothalamic neuropeptides, somatostatin (SRIF) and GRF, and their interrelation, in generating the sexually dimorphic GH secretory pattern we examined: 1) GH responsiveness to exogenous GRF and 2) the effects of immunoneutralization of endogenous SRIF and GRF on GH secretory dynamics, in free-moving male and female rats. In males, the GH response to 1 microgram rat(r)GRF(1-29)NH2 iv was significantly greater at peak compared to trough times of GH secretion (925.2 +/- 250.8 vs. 95.6 +/- 27.8 ng/ml; P less than 0.02), the latter known to be due to antagonization by the cyclic increased release of endogenous SRIF. In contrast, females failed to exhibit a time-dependent difference in GH responsiveness to GRF. Passive immunization with a specific antiserum to SRIF in males resulted in significant elevation of GH nadir levels but had no effect on GH peak amplitude. In contrast, immunoneutralization of endogenous SRIF in females caused a marked augmentation of plasma GH levels at all time points; there was a significant increase in GH peak amplitude (171.3 +/- 39.9 vs. 67.5 +/- 11.3 ng/ml; P less than 0.05), GH nadir (18.3 +/- 2.7 vs. 5.8 +/- 1.1 ng/ml; P less than 0.01) and mean 6-h plasma GH level (78.7 +/- 4.1 vs. 33.1 +/- 5.8 ng/ml; P less than 0.001), compared to normal sheep serum-treated controls. These results indicate that the pattern of hypothalamic SRIF secretion in females does not follow the male-like ultradian rhythm. Passive immunization with a specific antiserum to GRF obliterated spontaneous GH pulses in both sexes. Moreover, in females, anti-GRF serum attenuated GH nadir levels (4.3 +/- 1.7 vs. 21.4 +/- 3.5 ng/ml; P less than 0.01) indicating a physiological role for GRF in maintaining the elevated basal GH level of females, in addition to its important role in generating the episodic GH pulses. Taken together, these findings provide support for the hypothesis that, in female rats, the pattern of hypothalamic SRIF secretion into hypophyseal portal blood is continuous, rather than cyclical, as in the male; whereas in the case of GRF secretion, in addition to steady-state release which occurs at a higher level in females than males, there is also episodic GRF bursting which does not follow a specific rhythm, as in the male.(ABSTRACT TRUNCATED AT 400 WORDS)
生长激素（GH）分泌模式和体细胞生长速率存在显著的性别差异；然而，介导这种性别差异的机制尚不清楚。为了阐明下丘脑神经肽——生长抑素（SRIF）和生长激素释放因子（GRF）的生理作用及其相互关系，在自由活动的雄性和雌性大鼠中，我们研究了：1）GH对外源性GRF的反应性；2）内源性SRIF和GRF的免疫中和对GH分泌动力学的影响。在雄性大鼠中，静脉注射1微克大鼠（r）GRF（1-29）NH2后，GH分泌高峰时的反应显著大于低谷时（925.2±250.8对95.6±27.8纳克/毫升；P<0.02），已知后者是由于内源性SRIF循环性增加释放的拮抗作用。相比之下，雌性大鼠对GRF的GH反应性未表现出时间依赖性差异。用针对SRIF的特异性抗血清对雄性大鼠进行被动免疫，导致GH最低点水平显著升高，但对GH峰值幅度无影响。相反，对雌性大鼠内源性SRIF进行免疫中和，导致所有时间点血浆GH水平显著升高；GH峰值幅度显著增加（171.3±39.9对67.5±11.3纳克/毫升；P<0.05），GH最低点（18.3±2.7对5.8±1.1纳克/毫升；P<0.01）以及6小时平均血浆GH水平（78.7±4.1对33.1±5.8纳克/毫升；P<0.001），与正常绵羊血清处理的对照组相比。这些结果表明，雌性大鼠下丘脑SRIF分泌模式不遵循雄性样的超日节律。用针对GRF的特异性抗血清进行被动免疫消除了两性的自发性GH脉冲。此外，在雌性大鼠中，抗GRF血清降低了GH最低点水平（4.3±1.7对21.4±3.5纳克/毫升；P<0.01），表明GRF除了在产生间歇性GH脉冲中起重要作用外，在维持雌性大鼠基础GH水平升高方面也具有生理作用。综上所述，这些发现支持了以下假设：在雌性大鼠中，下丘脑SRIF分泌到垂体门脉血中的模式是持续的，而不是像雄性那样呈周期性；而对于GRF分泌，除了在雌性中比雄性更高水平的稳态释放外，还存在不遵循特定节律的间歇性GRF爆发，如同雄性一样。（摘要截短至400字）
