Administration of low dose pulsatile gonadotropin-releasing hormone (GnRH) to GnRH-deficient men regulates free alpha-subunit secretion

Abstract

Although pharmacological doses of GnRH and TRH stimulate free alpha-subunit (alpha-subunit) secretion from the pituitary, little is known about the pattern and control of alpha-subunit release under physiological circumstances. Euthyroid men with idiopathic hypogonadotropic hypogonadism, a condition of deficient GnRH release, provide a unique opportunity to study alpha-subunit secretion before and during administration of a physiological regimen of GnRH administration. Before GnRH therapy, six euthyroid IHH men with normal endogenous TSH secretion had circulating alpha-subunit levels close to or below assay detection limits, with a mean level less than 0.5 ng/ml. During 12-42 weeks of physiological GnRH replacement, serum alpha-subunit concentrations rose to a mean value of 2.07 +/- 0.3 (+/- SEM) ng/ml (P less than 0.01). After GnRH administration, alpha-subunit was released in a pulsatile pattern following each dose of GnRH and mirrored the secretory pattern of LH. Increases in serum alpha-subunit concentrations during GnRH administration were closely correlated with increases in LH (r = 0.91; P less than 0.01), but not FSH (r = 0.24; P = NS), levels. In addition, a situation in which LH secretion was clearly predominant and FSH levels were barely detectable was created by increasing the frequency of GnRH administration to every 30 min. In this circumstance, free alpha-subunit concentrations increased in conjunction with LH levels in the face of decreased FSH levels. We conclude that replacement of GnRH regulates both the level and pattern of alpha-subunit secretion in GnRH-deficient men, and that there is tight correlation of alpha-subunit with LH, but not with FSH, secretion.