Weinstock R S, Wright H N, Spiegel A M, Levine M A, Moses A M
Nature. 1986;322(6080):635-6. doi: 10.1038/322635a0.
The guanine nucleotide-binding stimulatory protein (Gs) couples hormone-receptor interaction to the activation of adenylate cyclase and the generation of cyclic AMP. Studies using frog neuroepithelium indicate that the sense of smell is mediated by a Gs-adenylate cyclase system, and this prompted us to test olfaction in the only known model of Gs deficiency in the animal kingdom, Gs-deficient (type 1a) pseudohypoparathyroidism (PHP), which occurs in humans. Such patients are resistant to the cAMP-mediated actions of several hormones. (Although Henkin has reported disturbances in the sense of smell in six patients with PHP, currently available biochemical measurements such as the cAMP response to parathyroid hormone (PTH) and determination of Gs activity were not reported and olfactory testing was limited.) In the present study, we found that all Gs-deficient patients had impaired olfaction when compared with PHP patients who had normal Gs activity (type 1b PHP, in which patients are resistant only to the action of PTH in the kidney). This is the first evidence of human olfactory impairment which can be related to Gs deficiency and suggests that Gs-deficient PHP patients may be resistant to cAMP-mediated actions in other non-endocrine systems.
鸟嘌呤核苷酸结合刺激蛋白（Gs）将激素 - 受体相互作用与腺苷酸环化酶的激活及环磷酸腺苷（cAMP）的生成偶联起来。对青蛙神经上皮的研究表明，嗅觉是由Gs - 腺苷酸环化酶系统介导的，这促使我们在动物界唯一已知的Gs缺乏模型——人类发生的Gs缺乏（1a型）假性甲状旁腺功能减退症（PHP）中测试嗅觉。这类患者对几种激素的cAMP介导作用具有抗性。（尽管亨金曾报道6例PHP患者存在嗅觉障碍，但未报告目前可用的生化测量结果，如对甲状旁腺激素（PTH）的cAMP反应及Gs活性测定，且嗅觉测试有限。）在本研究中，我们发现，与具有正常Gs活性的PHP患者（1b型PHP，这类患者仅对PTH在肾脏中的作用有抗性）相比，所有Gs缺乏的患者均存在嗅觉受损。这是人类嗅觉障碍与Gs缺乏相关的首个证据，表明Gs缺乏的PHP患者可能对其他非内分泌系统中cAMP介导的作用具有抗性。
