Control of LH secretory-burst frequency and interpulse-interval regularity in women

1 Departments of Statistics and 2 Internal Medicine and Obstetrics and Gynecology, General Clinical Research Center, University of Virginia, Charlottesville, Virginia 22908; and 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Medical and Graduate Schools of Medicine, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905 Submitted 27 March 2003 ; accepted in final form 23 June 2003 Hypothalamic neurons generate discrete bursts of gonadotropin-releasing hormone (GnRH) and thereby pulses of luteinizing hormone (LH) at randomly timed intervals centered on a probabilistic mean frequency. We tested the hypothesis that physiological mechanisms govern not only the number but also the stochastic dispersion of the GnRH/LH pulse-renewal process in humans; for example, in young women in the early (EF) and late (LF) follicular and midluteal (ML) phases of the menstrual cycle ( n = 18) and in postmenopausal individuals (PM, n = 16). To this end, we quantify stochastic interpulse variability by way of the order-independent, two-parameter Weibull renewal process (Keenan DM and Veldhuis J. Am J Physiol Regul Integr Comp Physiol 281: R1917–R1924, 2001) and the sequence-specific, model-free approximate-entropy statistic (ApEn) (Pincus SM. Proc Natl Acad Sci USA 88: 2297–2301, 1991). Statistical testing unveiled 1 ) reduced probabilistic mean LH secretory-burst frequency (lower of the Weibull distribution) in ML compared with each of EF, LF, and PM ( P < 0.001); 2 ) quantifiably more regular LH interburst-interval sets (elevated of the Weibull density) in PM than in each of EF, LF, and ML ( P < 0.01); 3 ) uniquely prolonged latency to maximal LH secretion within individual secretory bursts in ML ( P < 0.01); and 4 ) comparably mean random, sequential LH interburst-interval and mass values (normalized ApEn) among the distinct hormonal milieus. From these data, we postulate that sex steroids and age determine daily LH secretory-burst number, quantifiable pulse-renewal variability, and secretory-waveform evolution. age; reproduction; human; female; pituitary; hypothalamus; leuteinizing hormone Address for reprint requests and other correspondence: J. D. Veldhuis, Div. of Endocrinology and Metabolism, Dept. of Internal Medicine, Mayo Medical and Graduate Schools of Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN 55905 (E-mail: veldhuis.johannes{at}mayo.edu ).