Abstract
The aim of the present investigation was to lesion the noradrenergic system and to measure the effect on growth hormone (GH) secretion following peripheral administration of α2- and β-adrenoceptor agonists. Direct injection of these agonists into the paraventricular nucleus of the hypothalamus (PVN) and its effect on GH secretion were also investigated. Systemic administration of N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4, 60 mg/kg, injected i.p. 10 days prior to experimentation) significantly decreased the noradrenaline (NA) content of the hippocampus, frontal cortex and hypothalamus but had no effect on the dopamine (DA) or serotonin (5-HT) content of these areas. Bilateral injection of 6-hydroxydopamine (6-OHDA, 10 μg/μl, 14 days prior to experimentation) into the medial forebrain bundle (MFB) caused a greater reduction of NA and also decreased the DA and 5-HT content of the hypothalamus. Analysis of the PVN of the hypothalami of rats following 6-OHDA lesion of the MFB showed significantly decreased NA and 5-HT content. Neither DSP4 treatment nor 6-OHDA lesion of the MFB affected the clonidine (250 μg/kg, i.p.) induced stimulation of GH secretion. Injection of isoproterenol (1 mg/kg, i.p.) had varying effects on GH secretion. It stimulated GH release in control rats but not in DSP4 or MFB lesioned rats. Direct injection of clonidine (0.1 μg/μl) into the PVN significantly stimulated GH secretion, whereas injection of isoproterenol (2.5 μg/μl) into the PVN did not affect GH levels when compared to controls. The results of the present study do not support the hypothesis that hypoactivity of the central noradrenergic system may be the cause of the blunted GH response to clonidine observed in depressed patients.
Similar content being viewed by others
References
Lesch, K. P., and Rupprecht, R. 1989. Psychoneuroendocrine research in depression II. Hormonal responses to releasing hormones as a probe for hypothalamic-pituitary-end organ dysfunction. J Neural Transm 75:179–194.
Terry, L. C., and Martin, J. B. 1981. The effects of lateral hypothalamic medial forebrain stimulation and somatostatin antiserum on pulsatile growth hormone secretion in freely behaving rats: Evidence for a dual regulatory mechanism. Endocrinology 109:622–627.
Tuomisto, J. and Männisto, P. 1985. Neurotransmitter regulation of anterior pituitary hormones. Pharmacol Rev 37:249–1738.
Müller, E. E. 1987. Neural control of somatotropic function. Physiol Reviews 67:962–1053.
Krulich, L., Mayfield, M. A., Steele, M. K., McMillen, B. A., McCann, S. M. and Koenig, J. I. 1982. Differential effects of pharmacological manipulations of central α1- and α2-adrenergic receptors on the secretion of thyrotropin and growth hormone in male rats. Endocrinology 110:796–804.
Krieg, R. J., Johnson, J. H. and Adler, R. A. 1989. Growth hormone (GH) secretion in the pituitary-grafted male rat: In vivo effects of GH-releasing hormone and isoproterenol and in vitro release by individual somatotropes. Endocrinology 125:2273–2278.
Krieg, R. J., Perkins, S. N., Johnson, J. H., Rogers, J. P., Arimura, A., and Cronin, M. J. 1988. β-Adrenergic stimulation of growth hormone (GH) release in vivo, and subsequent inhibition of GH-releasing factor-induced GH secretion. Endocrinology 122:531–537.
Lesch, K-P., Laux, G., Erb, A., Pfüller, H., and Beckmann, H. 1987. Growth hormone (GH) responses to GH-releasing hormone in depression: Correlation with GH release following clonidine. Psychiat Res 25:301–310.
Niewenhuys, R., Geeraedts, L. M. G., and Veening, J. G. 1982. The medial forebrain bundle of the rat I. General introduction. J Comp Neurol 206:49–295.
Swanson, L. W., Sawchenko, P. E., and Lind, R. W. 1986. Regulation of multiple peptides in CRF parvocellular neurosecretory neurons: Implications for the stress response. Prog in Brain Res 68:169–190.
Ishikawa, K., Katakami, H., and Frohman, L. A. 1987. Neuroanatomic localization of the inhibitory effect of TRH on growth hormone secretion. Am J Physiol 253:E354-E359.
Checkley, S., and Arendt, J. 1984. Pharmacoendocrine studies of GH., PRL and Melatonin in patients with affective illness. Pages 165–190,in Brown, G. M., Koslow, S. and S. Reichlin (eds.), Neuroendocrinology and Psychiatric Disorder. Raven Press, New York.
Siever, L. J., and Uhde, T. W. 1984. New studies and perspectives on the noradrenergic receptor system in depression: Effects of the α2-adrenergic agonist clonidine. Biol Psychiatry 19:131–156.
Siever, L. J. and Davis, K. L. 1984. Dysregulation of the noradrenergic system in depression. Psychopharmacol Bull 20:500–504.
Amsterdam, J. D., Maislin, G., Skolnick, B., Berwish, N., and Winokur, A. 1989. Multiple hormone responses to clonidine administration in depressed patients and healthy volunteers. Biol Psychiatry 26:265–278.
Eriksson, E., and Modigh, K. 1984. Depression, α2-receptors and sex hormones: Neuroendocrine studies in the rat. Pages 161–178,in Usdin, E., Äsberg, M., Bertilsson, L. and SjÖgvist, F. (eds.), Frontiers in biochemical and pharmacological research in depression. Raven Press, New York.
Terry, L. C. 1984. Catecholamine regulation of growth hormone and thyrotropin in mood disorders. Pages 237–254,in Brown, G. M., Koslow, S., and Reichlin, S. (eds.), Neuroendocrinology and Psychiatric Disorder. Raven Press, New York.
Pellegrino, L. J., Pellegrino, A. S. and Cushman, A. J. 1979. A stereotaxic atlas of the rat brain. 2nd Ed. Plenum Press, New York.
Paxinos, G., and Watson, C. 1986. The rat brain in stereotaxic coordinates. 2nd Ed. Academic Press, New York.
Harmse, P. G., and Ojeda, S. R. 1974. A rapid and simple procedure for chronic cannulation of the rat jugular vein. J Applied Physiol 36:391–392.
Tannenbaum, G. S., and Ling, N. 1984. The interrelationship of growth hormone (GH)-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion. Endocrinology 115:1952–1957.
Palkovits, M., and Brownstein, M. J. 1988. Maps and guide to microdissection of the rat brain. Elsevier, NY.
Russell, V. A., Lamm, M. C. L., de Villiers, A. S., Taljaard, J. J. F., Chalton, D. O. 1985. Effects of combined administration of L-tryptophan and tricyclic antidepressants on alpha- and beta-adrenoceptors and monoamine levels in the rat brain. Neurochem Res 10:1661–1671.
Jaffer, A., Searson, A., Russell, V. A., and Taljaard, J. J. F. 1990. The effect of selective noradrenergic denervation on thyrotropin secretion in the rat. Neurochem Res 15:13–16.
Jaffer, A., Daniels, W. M. U., Russell, V. A. and Taljaard, J. J. F. 1990. The effect of medial forebrain bundle lesion on thyrotropin secretion in the rat. Neurochem Res 16:577–581.
Jonsson, G., Hallmam, H., Ponzio, F., and Ross, S. 1981. DSP4 N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine a useful denervation tool forcentral and peripheral noradrenaline neurons. Eur J Pharmacol 72:173–188.
Lookingland, K. J., Chapin, D. S., McKay, D. W., and Moore, K. E. 1986. Comparative effects of the neurotoxins N-chloroethyl-N-2-bromobenzylamine hydrochloride (DSP4) and 6-hydroxy-dopamine on hypothalamic noradrenergic, dopaminergic and 5-hydroxytryptaminergic neurons in the male rat. Brain Res 365:228–234.
Jaffer, A., Russell, V. A., and Taljaard, J. J. F. 1987. Noradrenergic and dopaminergic modulation of thyrotropin secretion in the rat. Brain Res 404:267–272.
Miki, N. Ono, M., and Shizume, K. 1984. Evidence that opiatergic α-adrenergic mechanisms stimulate rat growth hormone via growth hormone releasing factor (GRF). Endocrinology 114:1950–1952.
Kabayama, Y., Kato, Y., Murakami, Y., Tanaka, H., and Imura, H. 1986. Stimulation by alpha-adrenergic mechanisms of the secretion of growth hormone-releasing factor (GRF) from perifused rat hypothalamus. Endocrinology 119:432–434.
Willoughby, J. O., and Day, T. A. 1981. Central catecholamine depletion: Effects on physiological growth hormone and prolactin secretion. Neuroendocrinol 32:65–69.
Söderpalm, B., Andersson, L., Carlsson, M., Modigh, K., and Eriksson, E. 1987. Serotonergic influence on the growth hormone response to clonidine in rat. J Neural Transm 69:105–114.
Huang, X. Y., and McCann, S. M. 1983. Effect of β-adrenergic drugs on LH, FSH and growth hormone (GH) secretion in conscious, ovariectomized rats (41732). Proc Soc Exp Biol and Med 174:244–248.
Bluet-Pajot, M. T., Schaub, C., and Nassiet, J. 1978. Growth hormone response to hypoglycemia under gamma-hydroxybutyrate narco-analgesia in the rat. Neuroendocrinol 26:141–149.
Bluet-Pajot, M. T., Durand, D., Mounier, F., Schaub, C., and Kordon, C. 1982. Interaction of β-adrenergic agonists and antagonists with the stimulation of growth hormone release induced by clonidine or by morphine in the rat. J Endocrinol 94:327–331.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jaffer, A., Daniels, W.M.U., Russell, V.A. et al. Effects of α2- and β-adrenoceptor agonists on growth hormone secretion following lesion of the noradrenergic system of the rat. Neurochem Res 17, 1255–1260 (1992). https://doi.org/10.1007/BF00968409
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00968409