Hochberg Z, Bick T, Amit T
Department of Pediatrics, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
Proc Soc Exp Biol Med. 1994 Jul;206(3):249-53. doi: 10.3181/00379727-206-43753.
The pulsatile pattern of growth hormone (GH) secretion is synchronized with the GH-receptor (GHR) turnover and the ensuing GH-binding protein (GHBP). We investigated the effect of GH pulse frequency on the turnover of GHR, and tested the theoretical reciprocal impacts of GH, GHR, and GHBP in different species and clinical conditions. Male Sprague-Dawley rats were hypophysectomized (hypox) at 35 days of age. Two groups of 16 rats received a single or two iv injections of 10 micrograms human GH (hGH) at an interval of 45 min. They were killed 45, 90, or 135 min after the single or second injection. A third group of 25 hypox rats were given continuous sc infusion of hGH for 6 days. Liver membranes were prepared for hGH somatogenic binding. A bolus of GH at 45-min intervals expedited GHR turnover, and continuous GH resulted in faster turnover cycles of 90 min. The impact of GHBP on GH bioactivity was then calculated in human serum by a rabbit liver membrane displacement assay. Bioactivity was diminished by GHBP with increasing GH levels up to a point, within the physiological range, where GH bioactivity is gradually restored. Finally, simulation calculation of the bound and free fraction of GH over a typical pulse in man and male rat showed the changing relations of free/bound GH. In man free hormone predominates most of the pulse, whereas in rat free GH comprised a smaller fraction. Thus, the reciprocal effects of GH on GHR turnover and GHBP generation, and that of GHBP on GH t1/2 lead to self-perpetuation of high (mostly free) GH in downregulation of GHR and its turnover with resultant lower GHBP.
生长激素（GH）分泌的脉冲模式与生长激素受体（GHR）的更新以及随之产生的生长激素结合蛋白（GHBP）同步。我们研究了GH脉冲频率对GHR更新的影响，并测试了GH、GHR和GHBP在不同物种和临床条件下理论上的相互影响。35日龄的雄性Sprague-Dawley大鼠接受垂体切除术（hypox）。两组各16只大鼠分别单次或两次静脉注射10微克人GH（hGH），间隔45分钟。在单次或第二次注射后45、90或135分钟将它们处死。第三组25只hypox大鼠连续皮下输注hGH 6天。制备肝细胞膜用于hGH促生长结合试验。每隔45分钟注射一次大剂量GH加快了GHR的更新，持续给予GH则导致90分钟更快的更新周期。然后通过兔肝细胞膜置换试验计算人血清中GHBP对GH生物活性的影响。在生理范围内，随着GH水平升高，GHBP会降低GH生物活性，直到达到某一点时GH生物活性逐渐恢复。最后，对人和雄性大鼠典型脉冲期间GH的结合和游离部分进行模拟计算，显示了游离/结合GH的变化关系。在人身上，游离激素在大多数脉冲期间占主导，而在大鼠中游离GH所占比例较小。因此，GH对GHR更新和GHBP生成的相互作用，以及GHBP对GH半衰期的相互作用，导致在GHR下调及其更新过程中高（大多为游离）GH的自我延续，从而导致GHBP降低。
