Stimulation of Alpha-Adrenoceptors Facilitates the Release of Growth Hormone-Releasing Hormone from Rat Hypothalamus in vitro |
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Authors: | S. Tsagarakis Feng Ge L. H. Rees G. M. Besser A. Grossman |
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Affiliation: | Department of Endocrinology, St Bartholomew's Hospital, London EC1A 7BE, UK.;Department of Chemical Endocrinology, St Bartholomew's Hospital, London EC1A 7BE, UK. |
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Abstract: | While extensive evidence suggests that adrenoceptors play an important role in the control of growth hormone in the rat, there are few studies involving the direct measurement of growth hormone-releasing hormone (GHRH). We have therefore developed a radioimmunoassay for rat GHRH, and used it to investigate the modulation of GHRH release by noradrenaline from incubated rat hypothalamus in vitro. The GHRH radioimmunoassay had no significant cross-reactivity with other hypothalamic or GHRH-related peptides, and was sensitive to 4 pg/tube; intra- and interassay coefficients of variation were 6% and 12% respectively. Single incubated rat hypothalami produced a stable and readily measurable output of GHRH in successive 20 min incubations after an initial 60 min preincubation; the release of GHRH was increased in the presence of 56 mM KCI, but did not respond to KCI-depolarization when calcium was excluded from the medium. Stimulated GHRH release was identical to synthetic rat GHRH(1–43) on high-performance liquid chromatography and Sephadex G-75 chromatography. Noradrenaline stimulated GHRH secretion in a dose-dependent manner in the concentration range 10−10— 10−6M, with a plateau in response at 10−7M. Stimulation with noradrenaline 10−7M was blocked by idazoxan 10−5M and attenuated by thymoxamine 10−5M, but was unaffected by timolol 10−5M. Both the α2-adrenoceptor agonist guanfacine, and the α1-adrenoceptor agonist methoxamine, specifically stimulated GHRH secretion. It is concluded that noradrenaline stimulates the release of GHRH at both α1 and α2-adrenoceptors. |
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Keywords: | growth hormone-releasing hormone adrenoceptors noradrenergic guanfacine methoxamine |
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