Wormald P J, Millar R P, Kerdelhué B
Department of Chemical Pathology, University of Cape Town Medical School, Republic of South Africa.
J Clin Endocrinol Metab. 1989 Sep;69(3):612-5. doi: 10.1210/jcem-69-3-612.
Specific saturable high affinity receptors for substance-P (SP) are present in human pituitaries obtained post-mortem. The human pituitary SP receptor bound SP and two of its analogs, [D-Tyr0]SP and [D-Tyr0,Nor,Leu11]SP, with similar affinities (Kd, 1.76 X 10(-8), 3.53 X 10(-8), and 1.93 X 10(-8) mol/L, respectively). The fragments SP-(3-11) and SP-(7-10) had lower affinities for the receptor than SP (Kd, 9.24 X 10(-8) and 2.86 X 10(-7) mol/L, respectively). SP-(5-8) and SP-(1-4) were poorly bound by the receptor (Kd, greater than 10(-6) mol/L). The progressive decrease in binding with the removal of amino acid residues from the N- or C-termini of the molecule is similar to that observed in the rat. GnRH and TRH did not compete for the SP-binding sites. SP was able to inhibit GnRH-stimulated LH secretion from cultured human pituitary cells in a dose-dependent manner, while having no effect on GnRH-stimulated FSH secretion. Basal release of TSH, PRL, GH, and ACTH was unaffected by SP. These findings suggest that SP may have a physiological role in the regulation of LH secretion in man.
在死后获得的人垂体中存在P物质（SP）的特异性可饱和高亲和力受体。人垂体SP受体与SP及其两种类似物[D-Tyr0]SP和[D-Tyr0,Nor,Leu11]SP结合，亲和力相似（解离常数Kd分别为1.76×10⁻⁸、3.53×10⁻⁸和1.93×10⁻⁸mol/L）。片段SP-(3-11)和SP-(7-10)对该受体的亲和力低于SP（解离常数Kd分别为9.24×10⁻⁸和2.86×10⁻⁷mol/L）。SP-(5-8)和SP-(1-4)与该受体的结合较弱（解离常数Kd大于10⁻⁶mol/L）。随着分子N端或C端氨基酸残基的去除，结合逐渐减少，这与在大鼠中观察到的情况相似。促性腺激素释放激素（GnRH）和促甲状腺激素释放激素（TRH）不竞争SP结合位点。SP能够以剂量依赖的方式抑制培养的人垂体细胞中GnRH刺激的促黄体生成素（LH）分泌，而对GnRH刺激的促卵泡生成素（FSH）分泌没有影响。促甲状腺激素（TSH）、催乳素（PRL）、生长激素（GH）和促肾上腺皮质激素（ACTH）的基础释放不受SP影响。这些发现表明，SP可能在人类LH分泌的调节中具有生理作用。
