[125I]hGH Metabolism in Acromegaly: Effects of Chronic Treatment with 2-BR-α-Ergocryptine

Abstract
To assess the effects of 2-Br-α-ergocryptine (CB-154 Sandoz) on hGH metabolism, six acromegalic women were studied before and after 2 months of treatment with 10 mg bromocriptine/day. GH kinetics were evaluated by noncompartmental analysis of the plasma disappearance curve of immunoprecipitable [125I]human GH after pulse administration of the labeled hormone. MCR was increased in all acromegalics after treatment; the difference between the means [153 ± 11 vs. 200 ± 16 ml/min · m2 (mean ± SE)] was highly significant. Secretion rate (SR), measured as the product of MCR by integrated 12-h concentration, was decreased in four patients after treatment, while it was slightly increased in the other two. No change was found after treatment, either in initial distribution volume [2.0 ±0.1 before (B) vs. 2.1 ± 0.1 liters/m2 after (A)] or total distribution volume [5.0 ± 0.3 (B) vs. 5.4 ± 0.4 liters/m2 (A)]. Diffusion of GH from the intravascular pool, measured as reentry rate, was unchanged with treatment [66 ± 4 (B) vs. 76 ± 11 ml/min m2 (A)]. In conclusion, our study shows that in acromegaly, bromocriptine lowers plasma GH levels in two ways: 1) by increasing the MCR of the hormone, and 2) by reducing the SR. The mechanisms by which bromocriptine increased MCR of the GH are also suggested on the basis of kinetic results; like dopamine, bromocriptine could induce a redistribution of blood flows to different organs, thus resulting in a net increase of blood flow to the liver and kidneys which are the major catabolic sites of GH.