Bromocriptine improves GH levels in Obesity

J Clin Endocrinol Metab. 2008 Sep;93(9):3455-61

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.

-------

The figure really shows what's going on here, so I omitted the rest of the abstract. You can see that giving bromcriptine restored the pulsatile secretion of growth hormone in these obese patients. Basal GH secretion was not enhanced and also IGF-1 levels were not significantly changed.

Interestingly, other studies have been done looking at the effects of bromocriptine on other parameters. Theses studies showed that 24-hour glucose, insulin, and leptin levels were significantly reduced, whereas FFAs were enhanced after bromocriptine treatment.

See also:
J Clin Endocrinol Metab. 2006 Aug;91(8):3236-40.
Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1038-43.

Can we preserve muscle wasting in another way?

GH is very expensive. Another way to give growth hormone is to provide an orally based releasing agent. This is an article demonstrating the concept and clinical application.

"Dietary energy restriction induces a predictable catabolic response in normal subjects (4, 5). This loss of nitrogen is associated with a decrease in insulin-like growth factor-I (IGF-I) and an increase in GH (19, 20), suggesting GH resistance. However, the resistance is not absolute, because administration of exogenous GH will effect an increase in IGF-I and increase nitrogen retention (4, 5). Because MK-677 is a potent GH secretagogue, the present study was undertaken to determine whether MK-677 could reverse the catabolic response to dietary energy restriction in healthy volunteers. "

Abstract:

MK-677, an Orally Active Growth Hormone Secretagogue, Reverses Diet-Induced Catabolism1
M. G. Murphy, L. M. Plunkett, B. J. Gertz, W. He, J. Wittreich, W. M. Polvino2 and D. R. Clemmons
The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 2 320-325Copyright © 1998 by The Endocrine Society

The reversal of diet-induced negative nitrogen balance by GH suggests a possible therapeutic role for GH treatment in catabolic patients. A double-blind, randomized, placebo-controlled, two-period, cross-over study was designed to investigate whether MK-677, an orally active nonpeptide mimic of GH-releasing peptide, can reverse diet-induced protein catabolism. Eight healthy volunteers (ages 24–39 yr) were calorically restricted (18 kcal/kg·day) for two 14-day periods. During the last 7 days of each diet period, subjects received either oral MK-677 25 mg or placebo once daily. There was a 14- to 21-day washout interval between periods. During the first week of caloric restriction (i.e. diet alone), daily nitrogen losses were similar for both treatment groups (mean ± SE; MK-677 group -2.67 ± 0.40 g/day vs. placebo group -2.83 ± 0.26 g/day). During the second week (diet and study drug), mean daily nitrogen balance was 0.31 ± 0.21 g/day in the MK-677 treatment group compared with -1.48 ± 0.21 g/day in the placebo group

In conclusion:
MK-677 reverses diet-induced nitrogen wasting, suggesting that if these short-term anabolic effects are maintained in patients who are catabolic because of certain acute or chronic disease states, it may be useful in treating catabolic conditions.