Endocrine signaling provides one critical means of physiological communication within an organism. Many endocrine signals exhibit an episodic or pulsatile configuration. In an effort to provide a versatile and statistically based algorithm for investigating the regulation of endocrine pulse signals, we have formulated a computerized algorithm in which a pulse is defined as a statistically significant increase in a "cluster" of hormone values followed by a statistically significant decrease in a second cluster of values. The increase or decrease is judged in relation to the actual experimental error expressed by the replicates in the presumptive nadir and peak data clusters. The program permits the operator to specify the cluster sizes of test peaks and pre- and postpeak nadirs. This method is largely insensitive to unstable base-line hormone concentrations and is not adversely affected by varying pulse amplitudes, widths, or configurations within the endocrine series. In addition, the simple statistical basis for this algorithm renders it minimally dependent on explicit or a priori assumptions about rates of hormone secretion or disappearance. The program has been validated for false-positive errors against a wide range of intraseries coefficients of variation (4-52%). We have illustrated its performance for profiles of luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, adrenocorticotropic hormone, and cortisol and compared these episodic patterns with those of stable serum constituents (total serum protein and calcium), which do not exhibit pulsatile fluctuation.

We undertook a study of the separate and combined effects of age and sex on the pulsatile pattern of GH secretion. The 24-h secretory profile of GH was generated by 20-min sampling in 10 young women (aged 18-33 yr), 10 young men (aged 18-33 yr), 8 postmenopausal women (aged greater than 55 yr), and 8 older men (aged greater than 55 yr). A computer-assisted pulse analysis program was used to assess both total GH secretion, as reflected in the 24-h integrated GH concentration (IGHC), and pulsatile secretion, as denoted by pulse frequency, duration, amplitude, and the fraction of GH secreted in pulses during the 24-h period (FGHP). IGHC was significantly greater in women than in men (P less than 0.025) and greater in the young than in the old (P less than 0.003). The mean pulse amplitude, duration, and FGHP were each greater in the young (P less than 0.006, P less than 0.03, and P less than 0.0001, respectively), but not significantly different between the sexes. The mean pulse frequency was not affected by sex or age. The serum concentration of free estradiol, but not free testosterone, correlated with IGHC (r = 0.46; P less than 0.005), pulse amplitude (r = 0.53; P less than 0.001), and FGHP (r = 0.59; P less than 0.0002). After correcting for the effects of estradiol, neither sex nor age influenced IGHC or mean pulse amplitude, while the effect of age on FGHP was reduced from 81% to 29%. Of the indices of GH secretion, FGHP had the strongest correlation (r = 0.43; P less than 0.006) with somatomedin-C. Somatomedin-C declined significantly with age in both sexes. Our results indicate that sex and age have independent and interrelated effects on GH secretion. These effects can be largely accounted for by corresponding variations in endogenous estradiol levels. These observations suggest an amplifying action of estradiol on the neuroendocrine regulation of pulsatile GH release.