Estradiol supplementation in postmenopausal women attenuates suppression of pulsatile growth hormone secretion by recombinant human insulin-like growth factor type I.
BACKGROUND
Why pulsatile GH secretion declines in estrogen-deficient postmenopausal individuals remains unknown. One possibility is that estrogen not only enhances stimulation by secretagogues but also attenuates negative feedback by systemic IGF-I. SITE: The study took place at an academic medical center.


METHODS
Subjects were healthy postmenopausal women (n=25).


METHODS
The study included randomized assignment to estradiol (n=13) or placebo (n=12) administration for 16 d and randomly ordered administration of 0, 1.0, 1.5, and 2.0 mg/m2 recombinant human IGF-I sc on separate days fasting.


METHODS
Deconvolution analysis of pulsatile and basal GH secretion and approximate entropy (pattern-regularity) analysis were done to quantify feedback effects of IGF-I.


RESULTS
Recombinant human IGF-I injections increased mean and peak serum IGF-I concentrations dose dependently (P<0.001) and suppressed mean GH concentrations (P<0.001), pulsatile GH secretion (P=0.001), and approximate entropy (P<0.001). Decreased GH secretion was due to reduced secretory-burst mass (P=0.005) and frequency (P<0.001) but not basal GH release (P=0.52). Estradiol supplementation lowered endogenous, but did not alter infused, IGF-I concentrations while elevating mean GH concentrations (P=0.012) and stimulating pulsatile (P=0.008) and basal (P<0.001) GH secretion. Estrogen attenuated IGF-I's inhibition of pulsatile GH secretion (P=0.042) but was unable to restore physiological GH pulse frequency or normalize approximate entropy.


CONCLUSIONS
Short-term estrogen replacement in postmenopausal women selectively mutes IGF-I-mediated feedback on pulsatile GH secretion. Disinhibition of negative feedback thus confers a novel mechanism by which estrogen may obviate hyposomatotropism.
Veldhuis
Johannes D
JD
Department of Medicine, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu
Keenan
Daniel M
DM
Bailey
Joy N
JN
Adeniji
Adenborduin
A
Miles
John M
JM
Paulo
Remberto
R
Cosma
Mihaela
M
Soares-Welch
Cacia
C
D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D013006:Growth Hormone / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause; D011994:Recombinant Proteins / Q000097:blood / Q000494:pharmacology
D018972:Insulin-Like Growth Factor Binding Protein 3; D010919:Placebos; D011994:Recombinant Proteins; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone