Lanzi R, Tannenbaum G S
Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
Endocrinology. 1992 Apr;130(4):1822-8. doi: 10.1210/endo.130.4.1347739.
Exogenous GH is known to exert a negative feedback effect on its own responsiveness to GH-releasing factor (GRF); however, the mechanism is not known. In the present study we examined the time course of effects of a single sc administration of recombinant human (rh) GH on GH responsiveness to GRF and investigated the possible involvement of somatostatin (SRIF) in this response. Free-moving adult male rats were administered 200 micrograms rhGH, sc, at 0800 h and subsequently challenged with 1 microgram GRF-(1-29)NH2, iv, at times of spontaneous peaks (1100 and 1500 h) and troughs (1300 h) in GH secretion during a 6-h (1000-1600 h) sampling period. H2O-injected control rats exhibited the typical cyclic responsiveness to GRF stimulation, with GRF-induced GH release significantly greater during peak compared to trough periods of the GH rhythm. Pretreatment with rhGH 3 h before GRF injection markedly inhibited the GH response to GRF at a peak time [integrated GH release over 30 min, 1135 +/- 271 vs. 6372 +/- 1185 ng/ml.30 min in H2O-injected controls (mean +/- SE); P less than 0.01]. In striking contrast, 5 h after rhGH administration, there was a 6-fold augmentation of GH responsiveness to GRF compared to that in H2O-injected controls at a trough time (7032 +/- 1622 vs. 1128 +/- 216 ng/ml.30 min; P less than 0.01). High GH responsiveness to GRF was preserved 7 h after rhGH injection. Passive immunization of rhGH-treated rats with SRIF antiserum reversed the rhGH-induced blunted GH response at 3 h (7985 +/- 366 vs. 1705 +/- 431 ng/ml.30 min in rhGH-treated control rats given normal sheep serum; P less than 0.01) and completely restored GH responsiveness to levels as high as those in H2O-injected controls. These results demonstrate that 1) a single sc injection of rhGH markedly attenuates GH responsiveness to GRF acutely for about 3 h, but subsequently enhances somatotroph sensitivity to the stimulatory actions of GRF; and 2) the short term blunting of GRF-induced GH release by rhGH is due at least in part to increased release of endogenous SRIF. The subsequent potentiation of GH responsiveness to GRF is probably due to a SRIF-mediated build-up of pituitary GH stores in a readily releasable pool. Such a mechanism of GH autofeedback may play a physiological role in the genesis of pulsatile GH secretion.
已知外源性生长激素（GH）对其自身对生长激素释放因子（GRF）的反应性产生负反馈作用；然而，其机制尚不清楚。在本研究中，我们检测了单次皮下注射重组人生长激素（rhGH）对生长激素对生长激素释放因子反应性的影响时间进程，并研究了生长抑素（SRIF）在该反应中可能的作用。自由活动的成年雄性大鼠在0800时皮下注射200微克rhGH，随后在6小时（1000 - 1600时）采样期间，在生长激素分泌的自发峰值（1100和1500时）和谷值（1300时）时静脉注射1微克GRF - (1 - 29)NH₂进行激发试验。注射水的对照大鼠对GRF刺激表现出典型的周期性反应性，与生长激素节律的谷值期相比，GRF诱导的生长激素释放在峰值期明显更大。在GRF注射前3小时用rhGH预处理，在峰值时间显著抑制了生长激素对GRF的反应[30分钟内的整合生长激素释放量，注射水的对照大鼠为1135 ± 271 vs. 6372 ± 1185 ng/ml·30分钟（平均值±标准误）；P < 0.01]。与之形成鲜明对比的是，rhGH给药5小时后，与注射水的对照大鼠在谷值时间相比，生长激素对GRF的反应性增强了6倍（7032 ± 1622 vs. 1128 ± 216 ng/ml·30分钟；P < 0.01）。rhGH注射7小时后，对GRF的高反应性得以保留。用生长抑素抗血清对rhGH处理的大鼠进行被动免疫，可逆转rhGH在3小时诱导的生长激素反应减弱（给予正常绵羊血清的rhGH处理对照大鼠为7985 ± 366 vs. 1705 ± 431 ng/ml·30分钟；P < 0.01），并将生长激素反应性完全恢复到与注射水对照大鼠一样高的水平。这些结果表明：1）单次皮下注射rhGH在约3小时内急性显著减弱生长激素对GRF的反应性，但随后增强了生长激素细胞对GRF刺激作用的敏感性；2）rhGH对GRF诱导的生长激素释放的短期减弱至少部分是由于内源性生长抑素释放增加。随后生长激素对GRF反应性的增强可能是由于生长抑素介导的垂体生长激素储备在易于释放的池中积累。这种生长激素自身反馈机制可能在脉冲式生长激素分泌的发生中起生理作用。
