Actions of estrogen on pulsatile, nyctohemeral, and entropic modes of growth hormone secretion.
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.
Shah
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N
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.
Evans
W S
WS
Veldhuis
J D
JD
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
D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone