Estradiol potentiates ghrelin-stimulated pulsatile growth hormone secretion in postmenopausal women.
BACKGROUND
Ghrelin and an estrogen-rich milieu individually amplify pulsatile GH secretion by increasing the amount of hormone released per burst. However, how these distinct agonists interact in controlling pulsatile GH output is not known.


OBJECTIVE
The objective of the study was to test the hypothesis that elevated estradiol (E(2)) concentrations potentiate hypothalamo-pituitary responses to a near-physiological ghrelin stimulus.


METHODS
This was a double-blind, placebo-controlled, prospectively randomized, parallel-cohort study.


METHODS
The study was conducted at an academic medical center.


METHODS
Twenty-one postmenopausal women participated in the study.


METHODS
Eleven subjects received placebo (Pl) and 10 others E(2) transdermally in escalating doses over 3 wk to mimic late follicular-phase E(2) concentrations. Saline or a submaximally stimulatory amount of ghrelin (0.3 microg/kg) was infused iv on separate randomly ordered mornings fasting after 17-21 d of Pl or E(2) administration.


RESULTS
Outcomes included serum concentrations of E(2), ghrelin, GH, IGF-I, IGF binding protein (IGFBP)-1 and IGFBP-3, and the estimated mass and waveform of stimulated GH secretory bursts.


RESULTS
Administration of E(2) yielded late follicular-phase E(2) concentrations. Compared with Pl, E(2) did not alter ghrelin concentrations but reduced IGF-I and IGFBP-3 and elevated IGFBP-1 concentrations. Compared with saline, ghrelin infusion amplified pulsatile GH secretion by 7.1-fold (P < 0.01). The effect of E(2) alone was 2.0-fold placebo and that of combined ghrelin/E(2) 10.4-fold (P < 0.01). Ghrelin and E(2) accelerated initial GH release individually but nonadditively by more than 2-fold (P < 0.01).


CONCLUSIONS
Estrogen augments ghrelin's near-physiological stimulation of pulsatile GH secretion and mimics ghrelin's acceleration of initial GH release. Thus, we hypothesize that estrogen and a GH secretagogue act via independent as well as convergent mechanisms.
Veldhuis
Johannes D
JD
Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu
Keenan
Daniel M
DM
Iranmanesh
Ali
A
Mielke
Kristi
K
Miles
John M
JM
Bowers
Cyril Y
CY
D000368:Aged; D015331:Cohort Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D054439:Ghrelin; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D036361:Peptide Hormones / Q000097:blood / Q000494:pharmacology*; D017698:Postmenopause / Q000187:drug effects / Q000502:physiology*
D054439:Ghrelin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D036361:Peptide Hormones; D019382:Human Growth Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I