title: Actions of estrogen on pulsatile, nyctohemeral, and entropic modes of growth hormone secretion.
abstract: The neuroendocrine mechanisms by which estradiol drives growth hormone (GH) secretion in the human are poorly defined. Here we investigate estrogen's specific regulation of the 24-h pulsatile, nyctohemeral, and entropic modes of GH secretion in healthy postmenopausal women. Volunteers (n = 9) received randomly ordered placebo versus estradiol-17beta (1 mg micronized steroid twice daily orally) treatment for 7-10 days and underwent blood sampling at 10-min intervals for 24 h to capture GH release profiles quantitated in a high-sensitivity chemiluminescence assay. Pulsatile GH secretion was appraised via deconvolution analysis, nyctohemeral GH rhythms by cosinor analysis, and the orderliness of GH release patterns via the approximate entropy statistic. Mean (+/-SE) 24-h serum GH concentrations approximately doubled on estrogen treatment (viz., from 0.31 +/- 0.03 to 0.51 +/- 0.07 microgram/l; P = 0.033). Concomitantly, serum insulin-like growth factor-I (IGF-I), luteinizing hormone, and follicle-stimulating hormone concentrations fell, whereas thyroid-stimulating hormone and prolactin levels rose (P < 0.01). The specific neuroendocrine action of estradiol included 1) a twofold amplified mass of GH secreted per burst, with no significant changes in basal GH release, half-life, pulse frequency, or duration; 2) an augmented amplitude and mesor of the 24-h rhythm in GH release, with no alteration in acrophase; and 3) greater disorderliness of GH release (higher approximate entropy). These distinctive and dynamic reactions to estrogen are consistent with partial withdrawal of IGF-I's negative feedback and/or accentuated central drive to GH secretion.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine and National Science Foundation Center for Biological Timing, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
authors.forename: N
authors.initials: N
authors.lastname: Shah
authors.forename: W S
authors.initials: WS
authors.lastname: Evans
authors.forename: J D
authors.initials: JD
authors.lastname: Veldhuis
mesh_terms: D000368:Aged; D002940:Circadian Rhythm / Q000502:physiology*; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause; D011673:Pulsatile Flow
chemical_list: D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone