Paracrine regulation of growth hormone secretion by estrogen in women.
BACKGROUND
Paracrine regulation is emerging as a discrete control mechanism in the endocrine system. In hypogonadal men, stimulation of GH secretion by testosterone requires prior aromatization to estradiol, a paracrine effect unmasked by central estrogen receptor blockade with tamoxifen. In hypogonadal women, estrogen replacement via a physiological non-oral route fails to enhance GH secretion, indicating an absence of an endocrine effect. The aim was to investigate whether local estrogens produced from aromatization regulate GH secretion.


METHODS
We conducted an open-label, two-phase, crossover study.


METHODS
We compared the effects on GH secretion of tamoxifen with estradiol valerate in postmenopausal women. Ten women were treated with tamoxifen (10 and 20 mg/d) and estradiol valerate (2 mg/d) via oral route for 2 wk each, with a washout period of at least 6 wk.


METHODS
We measured the GH response to arginine and circulating levels of IGF-I and SHBG, markers of hepatic estrogen effect.


RESULTS
The GH response to arginine was reduced by 10- and 20-mg tamoxifen in a dose-dependent manner and potentiated significantly (P<0.05) by estradiol valerate. Mean IGF-I concentration was reduced significantly with high-dose tamoxifen (P<0.01) and estradiol valerate treatment (P<0.05), whereas mean SHBG levels rose with both (P<0.01).


CONCLUSIONS
Blunted GH response to stimulation occurring in the face of reduced IGF-I feedback inhibition with tamoxifen indicates that GH secretion was suppressed by estrogen receptor antagonism. Because circulating estradiol was unaffected, these data indicate a significant role of local estrogen in the central control of GH secretion. We conclude that aromatase mediates the paracrine control of GH secretion in women.
Birzniece
Vita
V
Garvan Institute of Medical Research, Department of Endocrinology, St. Vincent's Hospital, The University of New South Wales, Sydney, NSW, Australia.
Sata
Akira
A
Sutanto
Surya
S
Ho
Ken K Y
KK
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001120:Arginine / Q000494:pharmacology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D019899:Paracrine Communication / Q000187:drug effects* / Q000502:physiology; D017698:Postmenopause; D011863:Radioimmunoassay; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*
D012738:Sex Hormone-Binding Globulin; D013629:Tamoxifen; D019382:Human Growth Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D001120:Arginine