Bromocriptine reduces augmented thyrotropin secretion in obese premenopausal women.
BACKGROUND
Diurnal TSH secretion is enhanced in obese premenopausal women. Dopamine inhibits TSH secretion through activation of dopamine D(2) receptors (D(2)R). Dopamine D(2)R availability in the brain is reduced in obese humans in proportion to body adiposity. We hypothesized that deficient dopamine D(2)R signaling is involved in the enhanced TSH secretion associated with obesity.


OBJECTIVE
The effect of short-term bromocriptine treatment on spontaneous TSH secretion in obese women was studied while body weight and caloric intake remained constant.


METHODS
We conducted a prospective, fixed-order, crossover study in a Clinical Research Center.


METHODS
Seventeen obese women (body mass index, 33.2 +/- 0.6 kg/m(2)) were studied twice in the early follicular phase of their menstrual cycle.


METHODS
Subjects were treated for 8 d with placebo and bromocriptine.


METHODS
Blood was collected for 24 h at 10-min intervals, and TSH and leptin were analyzed with deconvolution and correlation techniques, approximate entropy, and cosine regression.


RESULTS
Bromocriptine reduced 24-h TSH secretion (placebo, 29.8 +/- 4.6 mU/liter . 24 h, vs. bromocriptine, 22.4 +/- 3.7 mU/liter . 24 h; P = 0.001), whereas free T(4) and total T(3) concentrations did not change. Bromocriptine administration reduced the mesor and amplitude of the 24-h rhythm without resetting the phase. The regularity of the subordinate TSH pattern and synchrony between leptin and TSH were unaffected by bromocriptine.


CONCLUSIONS
Activation of dopamine D(2)R by bromocriptine reverses enhanced diurnal TSH secretion in obese women. Thus, reduced dopaminergic neuronal signaling might be involved in the perturbation of the thyrotrope hormonal axis in obese premenopausal women.
Kok
Petra
P
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Roelfsema
Ferdinand
F
Frölich
Marijke
M
van Pelt
Johannes
J
Meinders
A Edo
AE
Pijl
Hanno
H
D001971:Bromocriptine / Q000494:pharmacology / Q000627:therapeutic use*; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D002149:Energy Intake; D005260:Female; D006207:Half-Life; D006801:Humans; D020738:Leptin / Q000097:blood; D009765:Obesity / Q000097:blood* / Q000188:drug therapy; D010919:Placebos; D017697:Premenopause / Q000187:drug effects / Q000502:physiology*; D011674:Pulse; D013972:Thyrotropin / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*
D020738:Leptin; D010919:Placebos; D001971:Bromocriptine; D013972:Thyrotropin