Totsuka Y, Nielsen T B, Field J B
Endocrinology. 1983 Sep;113(3):1088-95. doi: 10.1210/endo-113-3-1088.
The stimulation of adenylate cyclase by TSH was decreased 50-60% in crude membranes prepared from homogenates of bovine thyroid slices that had previously been incubated for 2 h with the hormone. The diminished response was not associated with any significant change in the binding capacity or affinity for 125I-labeled TSH. The apparent affinities of the desensitized adenylate cyclase for TSH or GTP were not different from those of the enzyme prepared from thyroid slices that had been incubated without TSH. Decreased adenylate cyclase responses to NaF, cholera toxin, or guanyl-5'-yl-imidodiphosphate were also observed in the desensitized membrane, whereas the enzyme responses to prostaglandin E1, GTP, or forskolin were not decreased. However, desensitization caused no decrease in the cholera toxin-catalyzed ADP ribosylation of the 40,000 mol wt polypeptide guanine nucleotide-binding component of the adenylate cyclase. The desensitized membranes showed basal adenylate cyclase activity similar to that of the control membranes using adenyl-5'-yl-imidodiphosphate as substrate in the absence of a nucleotide-regenerating system. These results suggest that the in vitro TSH-induced desensitization of thyroid adenylate cyclase reflects an alteration in the activation processes of the nucleotide regulatory protein.
在先前已与该激素孵育2小时的牛甲状腺切片匀浆制备的粗制膜中，促甲状腺激素（TSH）对腺苷酸环化酶的刺激作用降低了50 - 60%。反应减弱与对125I标记的TSH的结合能力或亲和力的任何显著变化无关。脱敏的腺苷酸环化酶对TSH或鸟苷三磷酸（GTP）的表观亲和力与从未用TSH孵育的甲状腺切片制备的酶的表观亲和力没有差异。在脱敏的膜中还观察到腺苷酸环化酶对氟化钠（NaF）、霍乱毒素或鸟苷-5'-亚氨基二磷酸的反应降低，而该酶对前列腺素E1、GTP或福斯高林的反应未降低。然而，脱敏并未导致霍乱毒素催化的腺苷酸环化酶40,000道尔顿分子量的鸟嘌呤核苷酸结合多肽成分的ADP核糖基化减少。在不存在核苷酸再生系统的情况下，以腺苷-5'-亚氨基二磷酸为底物时，脱敏的膜显示出与对照膜相似的基础腺苷酸环化酶活性。这些结果表明，体外TSH诱导的甲状腺腺苷酸环化酶脱敏反映了核苷酸调节蛋白激活过程的改变。
