Abstract
Many reports indicate that serotonin plays a role in the regulation of the hypothalamo-pituitary-adrenocortical axis. The present study was designed to elucidate whether the activation of the central serotonergic pathway enhances adrenocorticotropin and corticosterone secretion, and if so, whether the CRH and vasopressin neuronal systems could be mediating this effect. Intraperitoneal administration of a low dose of L-5-hydroxytryptophan (an aromatic L-amino acid precursor of serotonin synthesis; 20 mg/kg bw, 30 minutes before the sacrifice) in rats pretreated with pargyline (a brain mononoamine oxidase inhibitor, which enhances monoamine activity; 75 mg/Kg bw, 16 hours before the sacrifice) and carbidopa (a peripheral active inhibitor of the decarboxylation of aromatic L-amino acids, which would permit more monoamine precursor to be available to the brain; 50 mg/Kg bw, 90 minutes before the sacrifice) increased ACTH and corticosterone secretion in plasma. Such an effect was partially blocked by metergoline (a serotonin type-1 and -2 receptor blocker; 1 mg/Kg bw, 90 minutes before the sacrifice), but not by spiperone (a serotonin type-2 and dopamine receptor antagonist; 0.5 mg/Kg bw, 90 minutes before the sacrifice). The activation of the central serotonergic system enhanced the CRH content in the median eminence, whereas it decreased the content of this neuropeptide in the medial basal hypothalamus. These effects were fully abolished by metergoline, but not by spiperone pretreatment. The activation of the serotonergic pathway did not influence the vaso-pressinergic neuronal system. In vitro experiments using hypothalamic-median eminence fragments incubated with serotonin solutions indicate that this monoamine possesses a CRH releasing effect at concentrations of 1 μM or more. The CRH secreta-gogue activity of serotonin (1 μM) was completely blocked by metergoline (1 μM) but not by spiperone (1 μM). Conversely, serotonin did not induce a significant release of vasopressin at any of the concentrations assayed. These studies strongly suggest that the enhanced pituitary-adrenocortical function after the activation of the central serotonergic pathway could be due, at least in part, through the stimulation of the CRH but not the vasopressinergic neuronal system.
Similar content being viewed by others
References
Fuller R.W., Snoddy H.D. Effect of serotonin-releasing drugs on serum corti-costerone concentration in rats. Neuroendocrinology 31: 96, 1980.
Fuller R.W. Serotonergic stimulation of pituitary-adrenocortical function in rats. Neuroendocrinology 32: 118, 1981.
Rees L.H., Cook D.M., Kendall J.W., Allen C.F., Kramer R.M., Ratcliffe J.G., Knight R.A. A radioimmunoassay for rat plasma ACTH. Endocrinology 89: 254, 1971.
Mueller G.P., Twohy C.P., Chen H.T., Advis J.P., Meites J. Effects of L-tryptophan and restrain stress on hypothalamic and brain serotonin turnover, and pituitary TSH and prolactin release in rats. Life Sci. 18: 715, 1976.
Krieger D.T., Rizzo F. Serotonin mediation of circadian periodicity of plasma 17-hydroxycorticosteroids. Am. J. Physiol. 217: 1703, 1969.
Krieger D.T., Lauria M. Effectiveness of cyproheptadine in decreasing plasma ACTH in Nelson’s syndrome. J. Clin. Endocrinol. Metab. 43: 1179, 1976.
Spinedi E., Negro-Vilar A. Serotonin and adrenocorticotropin (ACTH) release: direct effects at the anterior pituitary level and potentiation of arginine vasopressin-induced ACTH release. Endocrinology 112: 1217, 1983.
Holmes M.C., DiRenzo G., Beckford U., Gillhman B., Jones M.T. Role of serotonin in the control of secretion of corti-cotrophin releasing factor. J. Endocrinol. 93: 151, 1982.
Telegdy G., Kardos M. Site of action of 5-hydroxytryptamine on the hy-pothalamo-pituitary-adrenal system in vitro. Acta Physiol. Acad. Sci. Hung. 46: 253, 1975.
Spinedi E., Rodriguez G. Angiotensin II and adrenocorticotropin release: mediation by endogenous corticotropin-releasing factor. Endocrinology 119: 1397, 1986.
Spinedi E., Negro-Vilar A. Angiotensin II and ACTH release: site of action and potency relative to corticotropin-releasing factor and vasopressin. Neuroendocrinology 37: 446, 1983.
Spinedi E., Giacomini M., Jacquier M-C., Gaillard R.C. Changes in the hypothalamo-corticotrope axis after bilateral adrenalectomy: evidence for a median eminence site of glucocorticoid action. Neuroendocrinology 53: 160, 1991.
Spinedi E., Aguado L., Chisari A., Cerrizo D. Monosodium-glutamate-induced hypothalamic dysfunction. Brain Dysfunction 1: 154, 1988.
Zar J.H. Biostatistical Analysis. Prentice-Hall, Englewood Cliffs, New Jersey, 1974.
Buckingham J.C. The influence of corticosteroids on the secretion of corticotropin and its hypothalamic releasing hormone. J. Physiol. 286: 331, 1979.
Sato T., Sato M., Shinsako J., Dallman M.F. Corticosterone-induced changes in hypothalamic corticotropin-releasing factor (CRF) content after stress. Endocrinology 97: 265, 1975.
Murakami K., Akana S., Dallman M.F., Ganong W.F. Correlation between the stress-induced corticotropin-releasing hormone content of the median eminence and hypothalamus and adrenocorticotropic hormone secretion. Neuroendocrinology 49: 233, 1989.
Fuller R.W., Snoddy H.D., Molloy B.B. Pharmacologic evidence for a serotonin neural pathway involved in hypothalamus-pituitary-adrenal function in rats. Life Sci. 19: 337, 1976.
Okada F., Saito Y., Fujieda T., Yamashita I. Monoamine changes in the brain of rats injected with L-5-hydroxytryptophan. Nature 238: 355, 1972.
Johnston C.A., Spinedi E., Negro-Vilar A. Aromatic L-amino acid decarboxylase activity in the rat median eminence, neurointermediate lobe and anterior lobe of the pituitary. Physiological and pharmacological implications for pituitary regulation. Neuroendocrinology 39: 54, 1984.
Bagdy G., Calogero A.E., Murphy D.L., Szemeredi K. Serotonin agonists cause parallel activation of the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis in conscious rats. Endocrinology 125: 2664, 1989.
Lesch K-P., Sohnle K., Poten B., Schoellnhammer G., Rupprecht R., Schulte H.M. Corticotropin and Cortisol secretion after central 5-hydroxytryptamine-1A (5-HT1A) receptor activation: effects of 5-HT receptor and β-adrenoceptor antagonists. J. Clin. Endocrinol. Metab. 70: 670, 1990.
Zimmermann H., Kaplan S.L., Ganong W.F. Evidence that the effects of 5-hydroxytryptophan on the secretion of ACTH and growth hormone in dogs are not mediated by central release of serotonin. Neuroendocrinology 34: 27, 1982.
Calogero A.E., Bernardini R., Margioris A.N., Bagdy G., Galluci W.T., Munson P.J., Tamarkin L., Tomai T.P., Brady L., Gold P.W., Chrousos G.P. Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by ex-planted rat hypothalami. Peptides 10: 189, 1989.
Calogero A.E., Bagdy G., Szemeredi K., Tartaglia M.E., Gold P.W., Chrousos G.P. Mechanisms of serotonin receptor agonist-induced activation of the hypothalamic-pituitary-adrenal axis in the rat.. Endocrinology 126: 1888, 1990.
Yehuda R., Meyer J.S. A role for serotonin in the hypothalamic-pituitary-adrenal response to insulin stress. Neuroendocrinology 38: 25, 1984.
Guillaume V., Grino M., Conte-Devolx B., Boudouresque F., Oliver C. Corticotropin-releasing factor increases in rat hypophysial portal blood during insulin-induced hypoglycemia. Neuroendocrinology 49: 676, 1989.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Spinedi, E., Gaillard, R.C. Stimulation of the hypothalamo-pituitary-adrenocortical axis by the central serotonergic pathway: involvement of endogenous corticotropin-releasing hormone but not vasopressin. J Endocrinol Invest 14, 551–557 (1991). https://doi.org/10.1007/BF03346866
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03346866