Veldhuis Johannes D, Bowers Cyril Y
Division of Endocrinology and Metabolism, Department of Internal Medicine, General Clinical Research Center, Mayo Medical and Graduate School of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Endocrine. 2003 Oct;22(1):25-40. doi: 10.1385/ENDO:22:1:25.
Technical, genetic, and clinical developments have unveiled a burgeoning array of novel effectors of GH secretion. The present appraisal of central neuroregulatory components of the somatotropic axis highlights a simplifying concept of ensemble control by the final common peptides, GH-releasing hormone (GHRH), GH-releasing peptide(s) (GHRP, ghrelin), and somatostatin. These potent signals act individually, antagonistically, and synergistically to direct pulsatile GH secretion. GHRH, GHRP/ghrelin, and somatostatin further adapt to autonegative feedback by GH and IGF-I. Estradiol modulates the impact of each of the primary peptidyl inputs; viz.: (i) enhances submaximally effective feedforward by discrete pulses of (injected) recombinant human GHRH-1,44-amide (as defined by increased agonistic potency and pituitary sensitivity); (ii) potentiates the submaximally stimulatory effects of GHRP-2, a hexapeptidyl mimetic of ghrelin; (iii) blunts dose-dependent inhibition of fasting GH secretion by somatostatin- 14; and (iv) relieves rhGH-enforced negative feedback on GHRP-2 (but not on basal, exercise, or GHRH)-stimulated GH secretion. The foregoing estrogenic activities collectively augment GH secretory burst mass by amplifying feedforward (via both GHRH and GHRP) and attenuating feedback (imposed by somatostatin and GH). Whether testosterone fully mimics the foregoing mechanistic actions of estradiol is not known. In conclusion, the present conceptual platform of tri-peptide-directed feedforward and GH/IGF-I-mediated feedback should aid in unraveling some of the complex regulatory dynamics targeted by sex-steroid hormones.
技术、遗传学及临床方面的进展揭示了一系列新兴的生长激素（GH）分泌效应器。目前对生长激素轴中枢神经调节成分的评估突出了一种简化的概念，即由最终的共同肽类——生长激素释放激素（GHRH）、生长激素释放肽（GHRP，胃饥饿素）和生长抑素进行整体控制。这些强效信号分别、拮抗及协同作用，以指导GH的脉冲式分泌。GHRH、GHRP/胃饥饿素和生长抑素还会通过GH和胰岛素样生长因子-I（IGF-I）进行自身负反馈调节。雌二醇调节每种主要肽类输入的影响，即：（i）通过（注射的）重组人GHRH-1,44-酰胺的离散脉冲增强次最大有效前馈（定义为激动剂效力和垂体敏感性增加）；（ii）增强GHRP-2（一种胃饥饿素的六肽模拟物）的次最大刺激作用；（iii）减弱生长抑素-14对空腹GH分泌的剂量依赖性抑制；以及（iv）减轻重组人生长激素（rhGH）对GHRP-2（但不对基础、运动或GHRH）刺激的GH分泌施加的负反馈。上述雌激素活性通过放大前馈（通过GHRH和GHRP两者）和减弱反馈（由生长抑素和GH施加）共同增加GH分泌脉冲量。睾酮是否完全模拟雌二醇的上述机制作用尚不清楚。总之，目前由三肽导向的前馈和GH/IGF-I介导的反馈的概念平台应有助于阐明性甾体激素所针对的一些复杂调节动态。
