title: Regulation of complex pulsatile and rhythmic neuroendocrine systems: the male gonadal axis as a prototype.
abstract: Hormone-secreting glands communicate via intermittent (pulsatile or rhythmic) signal exchange. Signals act upon target glands via implicit (not directly observable) stimulatory and inhibitory dose-response functions. Time delays operate, since secreted hormones do not arrive at or act on responsive cells instantaneously. Neuroendocrine systems are unique examples, therefore, of intermittent time-delayed dose-dependent homeostatic ensembles. Investigating such ensembles thus requires estimating secretion from plasma concentrations, recognizing biological time-delays and reconstructing unobserved feedforward (agonist) and feedback (antagonist) dose-response interfaces as illustrated primarily for the GnRH-LH-T-axis, and secondarily for the corticotropic and somatotropic axes. In this manner, each neuroendocrine system is viewed as a whole, rather than the sum of individual parts.
authors.affiliation: Department of Medicine, Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, Minnesota, United States of America. veldhuis.johannes@mayo.edu <veldhuis.johannes@mayo.edu>
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Keenan
authors.forename: Steven M
authors.initials: SM
authors.lastname: Pincus
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006066:Gonads / Q000502:physiology*; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D010913:Pituitary-Adrenal System / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013269:Stochastic Processes; D013739:Testosterone / Q000378:metabolism
chemical_list: D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006854:Hydrocortisone