Harvey S
Department of Physiology, University of Alberta, Edmonton, Canada.
J Endocrinol. 1993 Apr;137(1):35-42. doi: 10.1677/joe.0.1370035.
Benzodiazepines are pharmacological agents widely used for their anxiolytic and anticonvulsant properties. However, as these drugs are known to antagonize the binding and action of thyrotrophin-releasing hormone (TRH) in pituitary tissue, the possibility that they may modulate GH secretion was investigated in domestic fowl, in which TRH is a GH-releasing factor. Chlordiazepoxide (an antagonist of central-type benzodiazepine receptors) had no significant effect on the basal release of GH from incubated chicken pituitary glands, but at concentrations > 10 mumol/l chlordiazepoxide suppressed somatotroph responsiveness and sensitivity to TRH stimulation. At this concentration, chlordiazepoxide competitively displaced the binding of [3H]3-methyl-histidine2-TRH ([3H]MeTRH) to chicken pituitary membranes. The prior incubation of pituitary glands with chlordiazepoxide had no significant effect on the number of [3H]MeTRH-binding sites, which were also unaffected by the administration of chlordiazepoxide in vivo. However, contrary to its effects in vitro, chlordiazepoxide reduced basal GH secretion in vivo, whilst potentiating the GH response to systemic TRH challenge. These results demonstrate benzodiazepine antagonism of TRH-binding sites in domestic fowl and a biphasic modulation of GH secretion, which may be mediated through opposing actions at pituitary and central sites.
苯二氮䓬类药物是因其抗焦虑和抗惊厥特性而被广泛使用的药理剂。然而，由于已知这些药物会拮抗垂体组织中促甲状腺激素释放激素（TRH）的结合和作用，因此在家禽中研究了它们调节生长激素（GH）分泌的可能性，在家禽中TRH是一种生长激素释放因子。氯氮卓（一种中枢型苯二氮䓬受体拮抗剂）对孵育的鸡垂体腺中GH的基础释放没有显著影响，但在浓度>10μmol/L时，氯氮卓抑制了生长激素细胞对TRH刺激的反应性和敏感性。在此浓度下，氯氮卓竞争性地取代了[3H]3-甲基组氨酸2-TRH（[3H]MeTRH）与鸡垂体膜的结合。垂体腺预先与氯氮卓孵育对[3H]MeTRH结合位点的数量没有显著影响，体内给予氯氮卓也不影响这些位点。然而，与它在体外的作用相反，氯氮卓在体内降低了基础GH分泌，同时增强了GH对全身性TRH刺激的反应。这些结果证明了苯二氮䓬类药物在家禽中对TRH结合位点的拮抗作用以及对GH分泌的双相调节，这可能是通过在垂体和中枢位点的相反作用介导的。
