title: Control of LH secretory-burst frequency and interpulse-interval regularity in women.
abstract: 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 lambda 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 gamma 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.
authors.affiliation: Department of Statistics, General Clinical Research Center, University of Virginia, Charlottesville, 22908, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Keenan
authors.forename: William S
authors.initials: WS
authors.lastname: Evans
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D005498:Follicular Phase; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D008183:Luteal Phase; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008433:Mathematics; D010507:Periodicity; D017697:Premenopause
chemical_list: D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone