Serotonin pp 431-444 | Cite as

Role of Serotonin in the Hypothalamic Regulation of Pituitary Function

  • Ray W. Fuller
  • James A. Clemens
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 133)


One function of serotonin neurons in brain appears to be control of pituitary hormone secretion. The anterior lobe of the pituitary gland secretes adrenocorticotropic hormone (ACTH), prolactin, growth hormone, thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH); the secretion of these hormones is governed by releasing factors and in some cases by release-inhibiting factors from the hypothalamus. Regulation of the secretion of these factors apparently involves complex neural circuitry, but serotonin neurons seem to represent one link in the control mechanisms for most if not all of these pituitary hormones. We will review briefly some of the more recent pharmacologic evidence supporting such a role of serotonin neurons, focusing primarily on ACTH and prolactin, the two hormones of major interest in our laboratories.


Growth Hormone Luteinizing Hormone Dorsal Raphe Nucleus Serum Prolactin Pituitary Function 


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  1. Arendash, G. W., and Gallo, R. V., 1978, Serotonin involvement in the inhibition of episodic luteinizing hormone release during electrical stimulation of the midbrain dorsal raphe nucleus in ovariectomized rats, Endocrinol., 102:1199.CrossRefGoogle Scholar
  2. Arnold, M. A., and Fernstrom, J. D., 1978, Serotonin receptor antagonists block a natural, short term surge in serum growth hormone levels, Endocrinol., 103:1159.CrossRefGoogle Scholar
  3. Breese, G. R., Vogel, R. A., Kuhn, C. M., Mailman, R. B., Mueller, R. A., and Schanberg, S. M., 1978, Behavioral and prolactin responses to 5-hydroxytryptophan in rats treated Curing development with 5,7-dihydroxytryptamine, Brain Res., 155:263.PubMedCrossRefGoogle Scholar
  4. Chambers, J. W., and Brown, G. M., 1976, Neurotransmitter regulation of growth hormone and ACTH in the rhesus monkey. Effects of biogenic amines, Endocrinol., 98:420.CrossRefGoogle Scholar
  5. Clemens, J. A., Bennett, D. R., and Fuller, R. W., 1979, The effect of a tryptophan-free diet on prolactin and corticosterone release by serotonergic stimuli, Horm. Metabol. Res., in press.Google Scholar
  6. Clemens, J. A., Roush, M. E., and Fuller, R. W., 1978, Evidence that serotonin neurons stimulate secretion of prolactin releasing factor, Life Sci., 22:2209.PubMedCrossRefGoogle Scholar
  7. Clemens, J. A., Sawyer, B. D., and Cerimele, B., 1977, Further evidence that serotonin is a neurotransmitter involved in the control of prolactin secretion, Endocrinol., 100:692.CrossRefGoogle Scholar
  8. Cocchi, D., Gil-Ad, I., Panerai, A. E., Locatelli, V., and Muller, E. E., 1977, Effect of 5-hydroxytryptophan on prolactin and growth hormone release in the infant rat: evidence for different neurotransmitter mediation, Neuroendocrinol. 24:1.CrossRefGoogle Scholar
  9. Di Renzo, G.F., Quattrone, A., Schettini, G., and Preziosi, P., 1978, Effect of quipazine and fenfluramine, two serotonin-like drugs, on TSH secretion in basal and cold stimulated conditions in the rat, Life Sci., 24:498.Google Scholar
  10. Di Renzo, G. F., Quattrone, A., Schettini, G., and Preziosi, P., 1979, Effect of selective lesioning of secretion-containing neurons on the TSH-inhibiting action of d-fenfluramine in male rats, Life Sci., 24:489.PubMedCrossRefGoogle Scholar
  11. Dorsa, D. M., and Connors, M. H., 1979, Canine growth hormone responsiveness during pentobarbital anesthesia: a method for evaluating serotoninergic stimulatory action, Endocrinol., 104:101.CrossRefGoogle Scholar
  12. Eden, S., Bolle, P., and Modigh, K., 1979, Monoaminergic control of episodic growth hormone secretion in the rat: effects of reserpine, a-methyl-p-tyrosine, p-chlorophenylalanine, and haloperidol, Endocrinol., 105:523.CrossRefGoogle Scholar
  13. Fuller, R. W., and Clemens, J. A., 1979, 1-(m-Trifluoromethylphenyl)-piperazine, a serotonin agonist, increases serum corticosterone and prolactin concentration in rats. IRCS Med. Sci., 7:106.Google Scholar
  14. Fuller, R. W., Clemens, J. A., Slater, I. H., and Rathbun, R. C., 1978c, Neuroendocrine and behavioral studies with fluoxetine, an inhibitor of serotonin uptake in brain, In: “Neuropsychopharmacology: Proceedings of the Tenth Congress of the Collegium Internationale Neuro-Psychopharmacologicum,” P. Deniker, C. Radouco-Thomas and A. Villeneuve, ed., Pergamon Press, New York.Google Scholar
  15. Fuller, R. W., and Hemrick, S. K., 1978, Selective in vivo inhibition of monoamine oxidase in rat tissues by N- 2(o-chlorophenoxy)-ethyl]-cyclopropylamine, Proc. Soc. Exp. Biol. Med., 158:323.PubMedGoogle Scholar
  16. Fuller, R. W., Perry, K. W., and Molloy, B. B., 1975, Effect of 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine on the depletion of brain serotonin by 4-chloroamphetamine, J. Pharmacol. Exp. Ther., 193:796.Google Scholar
  17. Fuller, R. W., Schaffer, R. J., Roush, B. W., and Molloy, B. B., 1972, Drug disposition as a factor in the lowering of brain serotonin by chloroamphetamines in the rat, Biochem. Pharmacol., 21:1413.PubMedCrossRefGoogle Scholar
  18. Fuller, R. W., and Snoddy, H. D., 1977, Elevation of plasma corticosterone by swim stress and insulin-induced hypoglycemia in control and fluoxetine-pretreated rats, Endocr. Res. Commun., 4:11.PubMedCrossRefGoogle Scholar
  19. Fuller, R. W., and Snoddy, H. D., 1979, The effects of metergoline and other serotonin receptor antagonists on serum corticosterone in rats, Endocrinol. in press.Google Scholar
  20. Fuller, R. W., Snoddy, H. D., and Clemens, J. A., 1978a, The effect of quipazine, a serotonin receptor agonist, on serum corticosterone in rats, Endocr. Res. Commun., 5:161.CrossRefGoogle Scholar
  21. Fuller, R. W., Snoddy, H. D., and Hemrick, S. K., 1978b, Effects of fenfluramine and norfenfluramine on brain serotonin metabolism in rats, Proc. Soc. Exp. Biol. Med 157:202.Google Scholar
  22. Fuller, R. W., Snoddy, H. D., and Molloy, B. B., 1976, Pharmacologic evidence for a serotonin neural pathway involved in hypothalamus-pituitary-adrenal function in rats, Life Sci., 19:337.PubMedCrossRefGoogle Scholar
  23. Fuller, R. W., Snoddy, H. D., and Molloy, B. B., 1975, Potentiation of the L-5-hydroxytryptophan-induced elevation of plasma corticosterone levels in rats by a specific inhibitor of serotonin uptake, Res. Commun. Chem. Pathol. Pharmacol., 10:193.PubMedGoogle Scholar
  24. Jones, M. T., Hillhouse, E. W., and Burden, J., 1976, Effect of various putative neurotransmitters on the secretion of corticotrophin-releasing hormone from the rat hypothalamus in vitro - a model of the neurotransmitters involved, J. Endocrinol., 69:1.PubMedCrossRefGoogle Scholar
  25. Jordan, D., Poncet, C., Mornex, R., and Ponsin, G., 1978, Participation of serotonin in thyrotropin release. I. Evidence for the action of serotonin on thyrotropin releasing hormone release, Endocrinol. 103:414.CrossRefGoogle Scholar
  26. Kamberi, I. A., Mical, R. S., and Porter, J. C., 1970, Effect of anterior pituitary perfusion and intraventricular injection of catecholamines and indoleamines on LH release, Endocrinol., 87:1.CrossRefGoogle Scholar
  27. Kordon, C., and Glowinski, J., 1972, Role of hypothalamic monoaminergic neurons in the gonadotrophin release-regulating mechanisms, Neuropharmacol., 11:153.CrossRefGoogle Scholar
  28. Krulich, L., Vijayan, E., Coppings, R. J., Giachetti, A., McCann, S. M., and Mayfield, M. A., 1979, On the role of the central serotoninergic system in the regulation of the secretion of thyrotropin and prolactin: thyrotropin-inhibiting and prolactin-releasing effects of 5-hydroxytryptamine and quipazine in the male rat, Endocrinol. 105:276.CrossRefGoogle Scholar
  29. Marsden, C. A., Conti, J., Strope, E., Curzon, G., and Adams, R. N., 1979, Monitoring 5-hydroxytryptamine release in the brain of the freely moving unanesthetized rat using in vivo voltammetry, Brain Res., 171:85.PubMedCrossRefGoogle Scholar
  30. Martin, J. B., Durand, D., Gurd, W., Faille, G., Audet, J., and Brazeau, P., 1978, Neuropharmacological regulation of episodic growth hormone and prolactin secretion in the rat, Endocrinol. 102:106.CrossRefGoogle Scholar
  31. Meltzer, H. Y., Fang, V. S., Paul, S. M., and Kaluskar, R., 1976, Effect of quipazine on rat plasma prolactin levels, Life Sci., 19:1073.PubMedCrossRefGoogle Scholar
  32. Meltzer, H. Y., Fessler, R. G., Simonovic, M., and Fang, V. S., 1978, Stimulation of rat prolactin secretion by indolealkylamine hallucinogens, Psychopharmacol., 56:255.CrossRefGoogle Scholar
  33. Meyer, D. C., 1978, Hypothalamic and raphe serotonergic systems in ovulation control, Endocrinol., 103:1067.CrossRefGoogle Scholar
  34. Morgan, W. W., and Herbert, D. C., 1978, Elevation of serum prolactin levels after the inhibition of serotonin uptake, Endocrinol., 103:1016.CrossRefGoogle Scholar
  35. Okada, F., Saito, Y., Fujieda, T., and Yamashita, I., 1972, Monoamine changes in the brain of rats injected with L-5-hydroxytryptophan, Nature, 238:355.PubMedCrossRefGoogle Scholar
  36. Placheta, P., Singer, E., Kriwanek, W., and Hertting, G., 1976, Mepiprazole, a new psychotropic drug: effects on uptake and retention of monoamines in rat brain synaptosomes, Psychopharmacol., 48:295.CrossRefGoogle Scholar
  37. Popova, N. K., Maslova, L. N., and Naumenko, E. V., 1972, Serotonin and the regulation of the pituitary-adrenal system after deafferentation of the hypothalamus, Brain Res., 47:61.PubMedCrossRefGoogle Scholar
  38. Puhringer, W., Wirz-Justice, A., and Lancranjan, I., 1976, Mood elevation and pituitary stimulation after i.v. 1–5-HTP in normal subjects: evidence for a common serotoninergic mechanism, Neurosci. Letters, 2:349.CrossRefGoogle Scholar
  39. Rowland, D., Steele, M., and Moltz, H., 1978, Serotonergic mediation of the suckling-induced release of prolactin in the lactating rat, Neuroendocrinol., 26:8.CrossRefGoogle Scholar
  40. Ruzsas, C., Jozsa, R., and Mess, B., 1979, Inhibitory role of brain stem serotoninergic neuron system on thyroid function in rat, Endocrinol. Exp., 13:9.PubMedGoogle Scholar
  41. Sanders-Bush, E., and Steranka, L. R., 1978, Immediate and long-term effects of p-chloroamphetamine on brain amines, Ann. N.Y., Acad. Sci., 305:208.CrossRefGoogle Scholar
  42. Smythe, G. A., 1977, The role of serotonin and dopamine in hypothalamic-pituitary function, Clin. Endocrinol., 7:325.CrossRefGoogle Scholar
  43. Solem, J. H., and Brinck-Johnsen, T., 1965, An evaluation of a method for determination of free corticosteroids in minute quantities of mouse plasma, Scand. J. Clin. Lab. Invest., 17, Suppl. 80:1.Google Scholar
  44. Trulson, M. E., and Jacobs, B. L., 1976, Behavioral evidence for the rapid release of CNS serotonin by PCA and fenfluramine, Eur. J. Pharmacol. 36:149.PubMedCrossRefGoogle Scholar
  45. Weiner, R. E., and Ganong, W. F., 1978, Role of brain monoamines and histamine in regulation of anterior pituitary secretion, Physiol. Rev., 58:905.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Ray W. Fuller
    • 1
  • James A. Clemens
    • 1
  1. 1.The Lilly Research LaboratoriesEli Lilly and CompanyIndianapolisUSA

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