Substance P receptors in human pituitary: a potential inhibitor of luteinizing hormone secretion.

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.