title: Olfactory dysfunction in humans with deficient guanine nucleotide-binding protein.
abstract: 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.
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism; D004700:Endocrine System Diseases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000172:deficiency*; D006801:Humans; D000857:Olfaction Disorders / Q000209:etiology* / Q000378:metabolism; D011547:Pseudohypoparathyroidism / Q000145:classification / Q000150:complications* / Q000378:metabolism
chemical_list: D000242:Cyclic AMP; D019204:GTP-Binding Proteins