Estrogen elevates the peak overnight production rate of acylated ghrelin.
BACKGROUND
Acylated ghrelin is the putatively bioactive GH secretagogue.


OBJECTIVE
Estradiol (E2) stimulates the synthesis rather than inhibits the metabolic clearance of acylated ghrelin.


METHODS
The study took place at an academic medical center.


METHODS
Healthy postmenopausal women participated.


METHODS
Interventions included prospectively randomized, double-blind separate-day iv infusions of saline or five graded doses of ghrelin in estrogen-deficient (n=12) and E2-supplemented (n=8) women.


RESULTS
Metabolic clearance rate (MCR), volume of distribution, half-life, and secretion rate of acylated ghrelin were assessed.


RESULTS
In pilot iv bolus ghrelin infusions, the median half-lives of acylated and total ghrelin were 21 and 36 min (P<0.01), MCRs 58 and 8.1 liters/kg.d (P<0.01), and volumes of distribution of 1.0 and 0.32 liters/kg (P<0.01), respectively. Transdermal E2 supplementation for 3 wk increased peak nighttime acylated ghrelin concentrations from 99+/-12 to 141+/-34 pg/ml (P=0.039). Exposure to E2 did not alter the linear relationships between 1) plasma acylated ghrelin concentration and ghrelin infusion rate (638+/-12 slope units), 2) MCR of acylated ghrelin and ghrelin infusion rate (10+/-2.5 slope units), and 3) MCR and plasma concentration of acylated ghrelin (0.017+/-0.004 slope units). These data predict peak nighttime production rates of acylated ghrelin of 3.8+/-0.9 (E2) and 1.9+/-0.2 (no E2) ng/kg.min (P=0.039).


CONCLUSIONS
Acylated ghrelin has a multifold larger distribution volume and MCR than total ghrelin. An estrogenic milieu augments synthesis and/or acylation of ghrelin peptide without altering its MCR.
Paulo
Remberto C
RC
Department of Pediatrics, Endocrine Research Unit, Clinical Translational Research Center, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester, Minnesota 55901, USA.
Brundage
Richard
R
Cosma
Mihaela
M
Mielke
Kristi L
KL
Bowers
Cyril Y
CY
Veldhuis
Johannes D
JD
D000215:Acylation; D000328:Adult; D016903:Drug Monitoring; D002149:Energy Intake; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D054439:Ghrelin / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; 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; D007986:Luteinizing Hormone / Q000097:blood; D008657:Metabolic Clearance Rate; D011388:Prolactin / Q000097:blood; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D055815:Young Adult
D054439:Ghrelin; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone