Nature of Alpha Subunit Secretion in Men: Circadian Rhythms, Pulsatile Release and Secretory Profiles

Abstract

Alpha subunit complements LH as a marker of the activity of the hypothalamic GnRH pulse generator. To characterize episodes of alpha subunit release and to determine if a circadian pattern of alpha subunit secretion is present in man, spontaneous alpha subunit pulsatility was analyzed in six healthy young men by blood sampling every 5 min for 24 h. The resulting alpha subunit concentration time series were analyzed by two statistically based independent peak detection methods, and subjected to Fourier transformation to assess underlying circadian rhythms. Cross-correlation analyses and multiple parameter deconvolution were used to estimate the concordance of spontaneous and exogenous GnRH-stimulated LH and alpha subunit secretion. These analyses revealed that two independent discrete peak detection algorithms yielded similar estimates of spontaneous alpha subunit pulse frequency, namely, 21 +/- 1.1 (Cluster) and 21 +/- 1.5 (Detect) alpha subunit peaks/24 h. Sampling intensity markedly influenced the estimate of endogenous alpha subunit pulse frequency, inasmuch as estimates from 5-min sampling were significantly greater than those of 10-min or 20-min sampling. Fourier transformation unmasked a significant circadian alpha subunit rhythm in all six men, with maximal concentrations at 0836 h and an average amplitude of 28% of the 24-hr mean hormone concentration. Cross-correlation analysis of spontaneous glycoprotein release revealed that serum LH and alpha subunit concentrations were highly cross-correlated when considered simultaneously, but not at various lags. Finally, deconvolution analysis of exogenous GnRH-stimulated glycoprotein release disclosed distinct half-times of alpha subunit and LH clearance with virtually simultaneous underlying secretory bursts. These data indicate that human alpha subunit is secreted in both a circadian and a discrete pulsatile fashion at a pulse frequency that is significantly underestimated at conventional sampling rates. The approximately hourly alpha subunit interpulse interval (68 +/- 4.6 min) is similar to that reported earlier for LH in peripheral blood and for testosterone in gonadal vein blood in healthy men. Moreover, cross-correlation analysis of endogenous GnRH-driven alpha subunit and deconvolution analysis of exogenous GnRH-stimulated alpha subunit and LH secretion suggest that these glycoproteins are secreted virtually simultaneously, but have significantly different endogenous clearance properties. The remarkably similar in vivo pulse frequencies for alpha subunit, LH, and testosterone in man suggest that the release of these three hormones is coordinately regulated.