Biologic activities of growth hormone secretagogues in humans
Biologic activities of growth hormone secretagogues in humans
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DOI：
10.1385/endo:14:1:087
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发表时间：
2001-02-01
期刊：
影响因子：
3.7
通讯作者：
Camanni, F
中科院分区：
文献类型：
--
作者：
Ghigo, E;Arvat, E;Camanni, F
生长激素促分泌剂(GHs)是一类人工合成的多肽和非多肽分子，即使口服给药后仍具有强烈的、剂量依赖的和可重复性的生长激素(GH)释放活性。GHS通过作用于垂体和下丘脑的特定受体(GHS-R)来释放GH。GHS可能作为功能性生长抑素拮抗剂，同时增强CH释放激素(GHRH)分泌神经元的活性。GHS的CH释放效应不受性别的影响，但经历了显着的年龄差异。雌激素在青春期GH对GHS的反应中起主要作用，GHRH活性低下、生长抑素能高活性以及GHS样配体和受体活性降低可能是GHS在衰老过程中GH释放减少的原因。GHS的活性并不完全是CH的特异性。它们轻微的催乳素释放活性可能来自于直接的脑下垂体活动。在生理条件下，GHS的ACTH释放活性依赖于中枢作用；在垂体ACTH分泌肿瘤中对GHS-R的直接作用可能解释了库欣病对GHS的特殊ACTH和皮质醇高反应。GHS在其他中枢和外周内分泌和非内分泌组织中有特定的受体亚型，介导CH非依赖的生物学活动。GHS影响睡眠模式，刺激食物摄取，并有心血管活动。GHS在正常和肿瘤滤泡来源的人甲状腺组织中具有特异性结合，并抑制滤泡来源的肿瘤细胞系的增殖。Ghrelin是一种在胃和其他组织中合成的28个氨基酸的多肽，它的发现为这一领域的研究开辟了新的迷人前景。
Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl molecules with strong, dose-dependent, and reproducible growth hormone (GH)releasing activity even after oral administration. GHSs release GH via actions on specific receptors (GHS-R) at the pituitary and, mainly, at the hypothalamic levels. GHSs likely act as functional somatostatin antagonists and meantime enhance the activity of CH-releasing hormone (GHRH)-secreting neurons. The CH-releasing effect of GHSs is independent of gender but undergoes marked age-related variations. Estrogens play a major role in enhancing the GH response to GHSs at puberty, which GHRH hypoactivity, somatostatinergic hyperactivity and impaired activity of the the putative GHS-like ligand and receptors probably explain the reduced GH-releasing effect of GHSs in aging. The activity of GHSs is not fully specific for CH. Their slight prolactin-releasing activity probably comes from direct pituitary action. In physiological conditions, the ACTH-releasing activity of GHSs is dependent on central actions; a direct action on GHS-R in pituitary ACTH-secreting tumors likely explains the peculiar ACTH and cortisol hyperresponsiveness to GHSs in Cushing disease. GHSs have specific receptor subtypes in other central and peripheral endocrine and nonendocrine tissues mediating CH-independent biologic activities. GHSs influence sleep pattern, stimulate food intake, and have cardiovascular activities. GHs have specific binding in normal and neoplastic follicular derived human thyroid tissue and inhibit the proliferation of follicular-derived neoplastic cell lines. The discovery of ghrelin, a 28 amino acid peptide synthesized in the stomach but also in other tissues, has opened new fascinating perspectives of research in this field.