Interaction of clonidine and GHRH on GH secretion in vivo and in vitro.
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 micrograms clonidine orally followed by 50 micrograms GHRH 1-44 i.v. 2 h later, (2) 50 micrograms GHRH 1-44 i.v. followed by 150 micrograms clonidine orally 2 h later, (3) 150 micrograms clonidine orally followed by GHRH i.v. 30 min later, (4) 300 micrograms clonidine orally followed by 50 micrograms GHRH i.v. 3 h later and (5) 50 micrograms GHRH i.v. followed by 300 micrograms 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 micrograms 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 micrograms 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 GHRH-stimulated GH secretion. These findings are compatible with clonidine leading to stimulation of GH by inducing endogenous GHRH release.
Alba-Roth
J
J
Medizinische Klinik Innenstadt, University of Munich, FR Germany.
Losa
M
M
Spiess
Y
Y
Schopohl
J
J
Müller
O A
OA
von Werder
K
K
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology*; D004347:Drug Interactions; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism; D051381:Rats
D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D003000:Clonidine