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Short-Term Treatment with Bromocriptine Improves Impaired Circadian Growth Hormone Secretion in Obese Premenopausal Women

Departments of General Internal Medicine (P.K., A.E.M.), of Endocrinology and Metabolic Diseases (F.R., H.P.), and of Clinical Chemistry (M.F., J.v.P.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands

Address all correspondence and requests for reprints to: Professor H. Pijl, M.D., Ph.D., Leiden University Medical Center, Department of Internal Medicine (C4-83), P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: h.pijl{at}lumc.nl.

Context: 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.

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

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

Participants: 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.

Intervention(s): Eight days of treatment with B and placebo (Pl) was performed.

Main Outcome Measure(s): 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 µg/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.