To investigate the mechanism by which clonidine stimulates GH-secretion in vivo and in vitro, we studied its interaction with GHRH. In vivo: eight or six normal male subjects were submitted to five protocols: (1) 150 μg clonidine orally followed by 50 μg GHRH 1-44 i.v. 2 h later, (2) 50 μg GHRH 1-44 i.v. followed by 150 μg clonidine orally 2 h later, (3) 150 μg clonidine orally followed by GHRH i.v. 30 min later, (4) 300 μg clonidine orally followed by 50 μg GHRH i.v. 3 h later and (5) 50 μg GHRH i.v. followed by 300 μg clonidine orally 90 min later. In vitro: Rat anterior pituitary cells were coincubated with clonidine (10-11, 10-9, 10-7 and 10-5 M) and GHRH (0.005, 0.05, 10 nM) for 4 h. Results: 150 μg clonidine alone does not stimulate GH-secretion. Furthermore, the GH-increase was not significantly different when GHRH bolus was given before, after or together with clonidine. When 300 μg clonidine was given before GHRH GH-levels were significantly higher (max 28.6 ± 8.0 mU/l) at 90 min, compared to when clonidine was given after GHRH (max 7.8 ± 3.6 mU/l). The GHRH bolus after clonidine led to a significantly lower GH-increase (max 31.6 ± 17.0 mU/l) compared to the GHRH-induced GH-increase (max 47.2 ± 13.0 mU/l) before clonidine. In vitro, clonidine had no stimulatory effect on GNRH-stimulated GH secretion. These findings are compatible with clonidine leading to stimulation of GH by inducing endogenous GHRH release.
|Number of pages||7|
|Publication status||Published - 1989|
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