Estrogen supplementation selectively enhances hypothalamo-pituitary sensitivity to ghrelin in postmenopausal women.
BACKGROUND
Sex-steroid hormones amplify pulsatile GH secretion by unknown mechanisms. Ghrelin is the most potent natural GH secretagogue discovered to date. A plausible unifying postulate is that estradiol (E(2)) enhances hypothalamo-pituitary sensitivity to ghrelin (a physiological effect). The hypothesis is relevant to understanding the basis of hyposomatotropism in aging and other relatively hypogonadal states.


OBJECTIVE
Our objective was to test the hypothesis that E(2) supplementation potentiates ghrelin's stimulation of pulsatile GH secretion.


METHODS
The study was conducted at an academic medical center.


METHODS
Healthy postmenopausal women (n = 20) were included in the study.


METHODS
Separate-day iv infusions of saline vs. five graded doses of ghrelin were performed in volunteers prospectively randomly assigned to receive (n = 8) or not receive (n = 12) transdermal E(2) for 21 d were performed.


METHODS
GH secretion was estimated by deconvolution analysis and abdominal visceral fat mass determined by computerized axial tomography were calculated.


RESULTS
E(2) supplementation augmented ghrelin's stimulation of basal (nonpulsatile) GH secretion by 3.6-fold (P = 0.022), increased GH responses to low-dose ghrelin by 2.9-fold (P = 0.035), did not alter ghrelin efficacy, and elicited more regular patterns of acylated ghrelin concentrations during saline infusion (P = 0.033). Abdominal visceral fat negatively determined responses to ghrelin (R = -0.346; P < 0.005).


CONCLUSIONS
Transdermal E(2) supplementation potentiates GH secretion stimulated by physiological but not pharmacological concentrations of acylated ghrelin, and concomitantly regularizes patterns of bioactive ghrelin secretion in postmenopausal women. Accordingly, the estrogen milieu appears to control sensitivity of the hypothalamopituitary unit to acylated ghrelin.
Kok
Petra
P
Department of Internal Medicine, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, Minnesota 55905, USA.
Paulo
Remberto C
RC
Cosma
Mihaela
M
Mielke
Kristi L
KL
Miles
John M
JM
Bowers
Cyril Y
CY
Veldhuis
Johannes D
JD
D002940:Circadian Rhythm / Q000187:drug effects; D004351:Drug Resistance / Q000187:drug effects*; D004357:Drug Synergism; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D054439:Ghrelin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D009928:Organ Specificity / Q000187:drug effects; D017698:Postmenopause / Q000187:drug effects* / Q000378:metabolism
D054439:Ghrelin; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone