Clark R G, Robinson I C
Nature. 1985;314(6008):281-3. doi: 10.1038/314281a0.
The discovery of human pancreatic growth hormone releasing factors (GHRFs) and subsequent characterization of human hypothalamic GHRF has led to studies on the role of these peptides in stimulating growth hormone (GH) release, and attempts to use GHRF peptides to increase growth rates in short children are already underway. However, there is no experimental evidence in animals that exogenous GHRF promotes growth in vivo. Although anaesthetized rats release GH reproducibly in response to GHRF injections, the responses in conscious male rats are much more variable, perhaps because of their highly episodic endogenous GH secretory pattern. In contrast, female rats secrete GH in a more continuous pattern and respond reproducibly to repeated injections of GHRF. We report here that it is possible to establish a 'male' type of GH secretory pattern in normal female rats by long-term pulsatile intravenous (i.v.) infusions of the active human GHRF fragment GHRF (1-29)NH2. We found that this treatment accelerates growth and increases pituitary GH content, whereas continuous infusions of this GHRF fragment at the same daily dose are ineffective. Pulsatile, but not continuous GHRF also stimulates growth in animals made GHRF-deficient by neonatal monosodium glutamate treatment. Thus exogenous GHRF will stimulate growth in both GHRF-deficient and normal animals provided it is administered in an appropriate pattern.
人类胰腺生长激素释放因子（GHRFs）的发现以及随后对人类下丘脑GHRF的特性描述，引发了对这些肽在刺激生长激素（GH）释放中作用的研究，并且利用GHRF肽提高矮小儿童生长速率的尝试已经在进行中。然而，在动物实验中，尚无证据表明外源性GHRF能在体内促进生长。尽管麻醉大鼠对注射GHRF可重复性地释放GH，但清醒雄性大鼠的反应变化更大，这可能是由于其高度间歇性的内源性GH分泌模式。相比之下，雌性大鼠以更持续的模式分泌GH，并且对重复注射GHRF有可重复性反应。我们在此报告，通过长期脉冲式静脉内（i.v.）输注活性人GHRF片段GHRF（1 - 29）NH₂，有可能在正常雌性大鼠中建立一种“雄性”类型的GH分泌模式。我们发现这种治疗可加速生长并增加垂体GH含量，而以相同日剂量持续输注该GHRF片段则无效。脉冲式而非连续式GHRF也能刺激因新生期谷氨酸单钠处理而导致GHRF缺乏的动物生长。因此，外源性GHRF只要以适当模式给药，就能在GHRF缺乏和正常动物中刺激生长。
