Exogenous growth hormone inhibits growth hormone-releasing factor-induced growth hormone secretion in normal men.

Previous studies from this laboratory and by others in rats, monkeys, and humans support the concept that growth hormone (GH) can regulate its own secretion through an autofeedback mechanism. With the availability of human growth hormone-releasing factor (GRF), the possible existence of such a mechanism was reexplored by examining the effect of exogenous GH on the GH response induced by GRF-44-NH2 in six normal men (mean age, 32.4 yr). In all subjects the plasma GH response evoked by GRF-44-NH2 (1 microgram/kg i.v. bolus) was studied before and after 5 d of placebo (1 ml normal saline i.m. every 12 h), and then before and 12 h after 5 d of biosynthetic methionyl human GH (5 U i.m. every 12 h). The GH response to GRF (maximal increment over time 0 value) was significantly inhibited after GH treatment (0-1.3 vs. 2.3-11.2 ng/ml before treatment, P = 0.05), but was not significantly affected by placebo. This impaired pituitary response to GRF persisted for at least 24 h following exogenous GH treatment in two subjects who underwent further study. Serum somatomedin-C concentrations were significantly increased after 5 d of GH treatment (2.66-5.00 vs. 0.92-1.91 U/ml before treatment, P = less than 0.01). The impaired pituitary response to GRF may be mediated indirectly through somatomedin, somatostatin, by a direct effect of GH on the pituitary somatotropes, or by all of these mechanisms. These data suggest that after GH treatment, the blunted GH response to synthetic GRF is not solely a consequence of the inhibition of hypothalamic GRF secretion.     

胰岛素样生长因子1和成纤维细胞生长因子7与毛乳头细胞的生长

背景:毛乳头细胞凝集性生长与其诱导毛发生长有关.毛乳头细胞分泌的多种生长因子如胰岛素样生长因子1、成纤维细胞生长因子7可能对毛乳头细胞生长具有重要的影响.目的:观察正常人毛乳头细胞的增长与生长方式与胰岛素样生长因子1、成纤维细胞生长因子7的相关性.方法:采用二步酶消化法分离培养毛乳头细胞,免疫组化法和流式细胞仪分别检测两种生长因子在凝集性与非凝集性生长的毛乳头细胞中的表达,MTT法检测2,5～100 μg/L质量浓度胰岛素样生长因子1对人毛乳头细胞增殖的影响.结果与结论:胰岛素样生长因子1与成纤维细胞生长因子7均表达于细胞胞浆,但表达量随时间减弱,其中第3代明显比第9代毛乳头细胞中成纤维细胞生长因子7的表达强烈(P＜0.05).与对照组相比,不同质量浓度胰岛素样生长因子1均有明显促进毛乳头细胞增殖的作用(P＜0.05),其中以2.5 μg/L最为显著.提示毛乳头细胞的凝集性生长状态的改变可能与胰岛素样生长因子1、成纤维细胞生长因子7表达下降有关,胰岛素样生长因子1可明显刺激毛乳头细胞增殖.     

Keratinocyte growth factor

Mucositis occurs in over 90% of patients undergoing stem cell transplantation for hematological malignancies. It is associated with significant morbidity in the form of pain, dysphagia and decreased oral intake, as well as mortality. Palifermin is a recombinant keratinocyte growth factor that has been shown to be effective in decreasing the incidence, severity and duration of mucositis in Phase III trials. Improvement in patient functioning during hematopoietic stem cell transplants has also been reported. This review deals with the preclinical data and the clinical trials that have been carried out with this agent in patients with hematologic malignancies. In addition limited Phase I and II data on solid tumors is available and will be included.