Pong S S, Chaung L Y, Dean D C, Nargund R P, Patchett A A, Smith R G
Department of Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Mol Endocrinol. 1996 Jan;10(1):57-61. doi: 10.1210/mend.10.1.8838145.
The potential application of small molecules in GH therapy has recently become a topic of increasing interest. The spiroindoline MK-0677, the benzolactam L-692,429, and the peptides, GHRP-6 and hexarelin, have been shown to possess potent and selective GH-secretory activity in several species including human. Moreover, these synthetic GH secretagogues act on a signal transduction pathway distinct from that of GHRH. A specific high affinity binding site in porcine and rat anterior pituitary membranes that mediates the activity of these secretagogues has now been identified. The binding affinity of these structurally diverse secretagogues is tightly correlated with GH-secretory activity. The binding is Mg(2+)-dependent, is inhibited by GTP-gamma-S, and is not displaced by GHRH and somatostatin. The receptor is distinct from that for GHRH and has the properties of a new G-protein-coupled receptor. It is speculated that these GH secretagogues mimic an unidentified natural hormone that regulates GH secretion in concert with GHRH and somatostatin.
小分子在生长激素（GH）治疗中的潜在应用近来已成为一个愈发受关注的话题。螺吲哚啉MK - 0677、苯并内酰胺L - 692,429以及肽类GHRP - 6和六元瑞林，已被证明在包括人类在内的多个物种中具有强大且选择性的GH分泌活性。此外，这些合成的GH促分泌剂作用于一条与生长激素释放激素（GHRH）不同的信号转导途径。现已在猪和大鼠的垂体前叶膜中鉴定出一个介导这些促分泌剂活性的特异性高亲和力结合位点。这些结构各异的促分泌剂的结合亲和力与GH分泌活性紧密相关。该结合依赖Mg(2+)，受GTP - γ - S抑制，且不会被GHRH和生长抑素取代。该受体与GHRH的受体不同，具有新型G蛋白偶联受体的特性。据推测，这些GH促分泌剂模拟了一种尚未明确的天然激素，该激素与GHRH和生长抑素协同调节GH分泌。
