Short-term treatment with bromocriptine improves impaired circadian growth hormone secretion in obese premenopausal women.
BACKGROUND
A profound reduction of spontaneous as well as stimulated GH secretion has been consistently observed in obesity. Dopamine promotes GH release through activation of dopamine D2 receptors (D2Rs). Dopamine D2R availability in the brain is reduced in obese humans in proportion to body adiposity. We hypothesized that impaired dopamine D2R signaling is mechanistically involved in the deficient GH secretion associated with obesity.


OBJECTIVE
To test this hypothesis, we studied the effect of short-term bromocriptine (B) (a D2R agonist) treatment on spontaneous 24-h GH secretion in obese women, while body weight and caloric intake remained constant.


METHODS
This was a prospective, fixed order, cross-over study.


METHODS
The study was performed in the Clinical Research Center at Leiden University Medical Center.


METHODS
There were 18 healthy obese women (body mass index 33.2 +/- 0.6 kg/m2) studied twice in the early follicular phase of their menstrual cycle.


METHODS
Eight days of treatment with B and placebo (Pl) was performed.


METHODS
Blood was collected during 24 h at 10-min intervals for determination of GH concentrations. GH secretion parameters were calculated using deconvolution analysis.


RESULTS
Short-term treatment with B significantly enhanced diurnal GH secretion (Pl 121.4 +/- 16.4 vs. B 155.4 +/- 15.2 microg/liter(volume of distribution).24 h; P = 0.01), whereas IGF-I concentrations remained constant (Pl 22.4 +/- 2.4 vs. B 21.8 +/- 1.6 nmol/liter; P = 0.928).


CONCLUSIONS
Activation of dopamine D2Rs by B favorably affects impaired nyctohemeral GH secretion in obese women. Reduced dopaminergic neuronal signaling might be involved in the pathogenesis of obesity associated hyposomatotropism.
Department of General Internal Medicine, Leiden University Medical Center, RC Leiden, The Netherlands.
Petra
P
Kok
Ferdinand
F
Roelfsema
Marijke
M
Frölich
Johannes
J
van Pelt
A Edo
AE
Meinders
Hanno
H
Pijl
D000328:Adult; D001971:Bromocriptine / Q000627:therapeutic use*; D021081:Chronobiology Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000627:therapeutic use; D005260:Female; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010919:Placebos; D017697:Premenopause / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D018491:Dopamine Agonists; D007328:Insulin; D020738:Leptin; D010919:Placebos; D019382:Human Growth Hormone; D001971:Bromocriptine