Skip to main content
Log in

Direct actions of serotonin on gonadotropin-II and growth hormone release from goldfish pituitary cells: interactions with gonadotropin-releasing hormone and dopamine and further evaluation of serotonin receptor specificity

  • Published:
Fish Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

In this study, the direct actions of serotonin (5HT) on gonadotropin (GTH)-II and growth hormone (GH) release in the goldfish were tested at the pituitary cell level. 5HT (10 nM - 10 µM) stimulated GTH-II but inhibited GH release from perifused goldfish pituitary cells in a dose-dependent manner. The minimal effective dose of 5HT tested to suppress basal GH secretion (10 nM) was 10-fold lower than that to stimulate GTH-II release (100 nM). The GTH-II releasing effect of 5HT was abolished by repeated 5HT treatment (10 µM) whereas the corresponding inhibition on GH release was unaffected. These results suggest that 5HT receptors on goldfish gonadotrophs and somatotrophs exhibit intrinsic differences in terms of sensitivity to stimulation and resistance to desensitization. Salmon GTH-releasing hormone (sGnRH, 100 nM) stimulated GTH-II and GH release from goldfish pituitary cells. The GTH-II releasing action of sGnRH was unaffected by simultaneous treatment of 5HT (1 µM). However, the corresponding GH response to sGnRH (100 nM) was inhibited. In the goldfish, dopamine is known to stimulate GH release through activation of pituitary D1 receptors. In the present study, the GH-releasing action of dopamine (1 µM) and the D1 agonist SKF38393 (1 µM) was significantly reduced by 5HT (1 µM). To examine the receptor specificity of 5HT action, the effects of 5HT1 and 5HT2 analogs on GTH-II and GH release were tested in goldfish pituitary cells. The 5HT1 agonist 8OH DPAT (0.1 and 1µM) and 5HT2 agonist α methyl 5HT (0.1 1µM) mimicked the GTH-II releasing effect of 5HT. The 5HT1 agonist 8OH DPAT (0.1 and 1µM) also stimulated GH release but the 5HT2 agonist α methyl 5HT (0.1 and 1µM) was inhibitory to basal GH secretion. In addition, 5HT (1µM) -stimulated GTH-II release was abolished by the 5HT1 antagonist methiothepin (10µM) and 5HT2 antagonist mianserin (10µM). Similarly, the inhibitory action of 5HT (1µM) on basal GH release was blocked by the 5HT2 antagonist mianserin (10µM). The 5HT1 antagonist methiothepin (10µM) was not effective in this regard. These results, taken together, indicate that 5HT exerts its regulatory actions on GTH-II and GH release in the goldfish directly at the pituitary cell level, probably through interactions with other regulators including sGnRH and dopamine. The GTH-II releasing action of 5HT is mediated through 5HT2 and possibly 5HT1 receptors. The inhibition of 5HT on basal GH release is mediated through 5HT2 receptors only. Apparently, 5HT1 receptors are not involved in this inhibitory action. In this study, a paradoxical stimulatory component of 5HT on GH release by activating 5HT1 receptors is also implicated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Armario, A. Marti, O., Gavalda, A. and Lopez-Calderon, A. 1993. Evidence for the involvement of serotonin in acute stress-induced release of luteinizing hormone in the male rat. Brain Res. Bull. 31: 29–31.

    Article  PubMed  Google Scholar 

  • Bagdy, G., Calogero, A.E., Murphy, D.L. and Szemeredi, K. 1989. Serotonin agonists cause parallel activation of the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis in conscious rats. Endocrinology 125: 2664–2669.

    PubMed  Google Scholar 

  • Bendotti, C., Tarizzo, G., Fumagalli, F., Baldessari, S. and Samanin, R. 1993. Increased expression of preproneuropeptide Y and preprosomatostatin mRNA in striatum after selective serotonergic lesions in rats. Neurosci. Lett. 160: 197–200.

    Article  PubMed  Google Scholar 

  • Calogero, A.E., Bernardini, R., Margioris, A.N., Bagdy, G., Gallucci, W.T., Munson, P.J., Tamarkin, L., Tomai, T.P., Brady, L., Gold, P.W. and Chrousos, G.P. 1989. Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by explanted rat hypothalami. Peptides 10: 189–193.

    Article  PubMed  Google Scholar 

  • Chang, J.P., Cook, H., Freedman, G.L., Wiggs, A.J., Somoza, G.M., De Leeuw, R. and Peter, R.E. 1990. Use of a pituitary cell dispersion method and primary culture system for the studies of gonadotropin-releasing hormone action in the goldfish, Carassius auratus. I. Initial morphological, static, and cell column perifusion studies. Gen. Comp. Endocrinol. 77: 256–273

    PubMed  Google Scholar 

  • De Los Frailes, M.T., Cacicedo, L., Lorenzo, M.J., Tolon, R.M., Fernandez, G. and Sanchez Franco, F. 1993. Neurotransmitter regulation of somatostatin secretion by fetal rat cerebral cortical cells in culture. J. Endocrinol. Invest. 16: 661–668.

    PubMed  Google Scholar 

  • Dow, R.C., Williams, B.C., Bennie, J., Carroll and Fink, G. 1994. A central 5HT2 receptor mechanism plays a key role in the proestrous surge of luteinizing hormone in the rat. Psychoneuroendocrinology 19: 395–399.

    Article  PubMed  Google Scholar 

  • Ekstrom, P. and Van Veen, T. 1984. Distribution of 5-hydroxytryptamine (serotonin) in the brain of the teleost, Gasterosteus aculeatus L. J. Comp. Neurol. 226: 307–320.

    PubMed  Google Scholar 

  • Frankenhuis-Van Den Heuvel, T.H.M. and Nieuwenhuys, R. 1984. Distribution of serotonin immunoreactivity in the diencephalon and mesencephalon of the trout, Salmo gairdneri. Anat. Embryol. 169: 193–204.

    Article  PubMed  Google Scholar 

  • Glaser, T., Dompert, W.U., Schuurman, T., Spencer Jr., D.J. and Traber, J. 1987. Differential pharmacology of the novel 5-HT receptor ligands 8-hydroxy DPAT, Bay 1531, and ipsapirone. In Brain 5-HT Receptors. pp. 106–125. Edited by C.T. Dourish, S. Ahlenius, and P.H. Hutson. Ellis Horwood, Chichester.

    Google Scholar 

  • Habibi, H.R. 1991a. Desensitization to native molecular forms of gonadotropin-releasing hormone in the goldfish pituitary: dependence on pulse frequency and concentration. Gen. Comp. Endocrinol. 84: 205–217.

    Google Scholar 

  • Habibi, H.R. 1991b. Homologous desensitization of gonadotropin-releasing hormone (GnRH) receptors in the goldfish pituitary: effects of native GnRH peptides and a synthetic GnRH antagonist. Biol. Reprod. 44: 275–283.

    PubMed  Google Scholar 

  • Holloway, A.C., Sheridan, M.A. and Leatherland, J.F. 1997. Estradiol inhibits plasma somatostatin 14 (SRIF-14) levels and inhibits the response of somatotrophic cells to SRIF-14 challenge in vitro in rainbow trout, Oncorhynchus mykiss. Gen. Comp. Endocrinol. 106:407–414.

    Article  PubMed  Google Scholar 

  • Hoyer, D., Clarke, D.E., Fozard, J.R., Hartig, P.R. Martin, G.R., Mylecharane, E.J., Saxena, P.R. and Humphrey, P.P.A. 1994. International union of pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol. Rev. 46, 157–203.

    PubMed  Google Scholar 

  • Humphrey, P.P.A., Hartig, P. and Hoyer, D. 1993. A proposed new nomenclature for 5-HT receptors. TIPS 14: 233–236.

    PubMed  Google Scholar 

  • Kacsoh, B., Toth, B.E. and Crosvenor, C.E. 1993. Neuroendocrine control of immuno-reactive growth hormone and bioactive prolactin secretion in neonatal rats: Ontogeny and interactions between the serotonergic, cholinergic, and alpha-adrenergic systems. Neuroendocrinology 57: 195–203.

    PubMed  Google Scholar 

  • Kah, O., Anglade, I., Lepretre, E., Dubourg, P. and De Monbrison, D. 1993. The reproductive brain in fish. Fish Physiol. Biochem. 11: 85–98.

    Google Scholar 

  • Kah, O. and Chambolle, P. 1983. Serotonin in the brain of the gold-fish, Carassius auratus: an immunohistochemical study. Cell Tiss. Res. 234: 319–333.

    Article  Google Scholar 

  • Khan, I.A. and Thomas, P. 1992. Stimulatory effects of serotonin on maturational gonadotropin release in the Atlantic croaker, Micropogonias undulatus. Gen. Comp. Endocrinol. 88: 388–396.

    PubMed  Google Scholar 

  • Khan, I.A. and Thomas, P. 1993. Immunocytochemical localization of serotonin and gonadotropin-releasing hormone in the brain and pituitary gland of the Atlantic croaker Micropogonias undulatus. Gen. Comp. Endocrinol. 91: 167–180.

    Article  PubMed  Google Scholar 

  • Lacau-Mengido, I.M., Libertun, C. and Becu-Villalobos, D. 1996. Different serotonin receptor types participate in 5-hydroxytryptophan-induced gonadotropins and prolactin release in the female infantile rat. Neuroendocrinology 63: 415–421.

    PubMed  Google Scholar 

  • Le Coore, S. and Chemineau, P. 1993. Control of photoperiodic inhibition of luteinizing hormone secretion by dopaminergic and serotonergic systems in ovariectomized Ile-de-France ewes supplemented with oestradiol. J. Repr. Fert. 97: 367–373.

    Google Scholar 

  • Leysen, J.E., Awouters, F., Kennis, L., Laduron, P.M., Vanderberk, J. and Janssen, P.A.J. 1981. Receptor binding profile of R41468, a novel antagonist at 5-HT2 receptors. Life Sci. 28: 1015–1022.

    Article  PubMed  Google Scholar 

  • Leung, M.Y., Chang, J.P., Chow, B.K.C. and Wong, A.O.L. 1997. Pituitary adenylate cyclase-activating polypeptide (PACAP) functions as a novel growth hormone (GH)-releasing factor in the goldfish. Program and Abstracts, the XIII Int. Congr. Comp. Endocrinol., Abstract (accepted).

  • Lopez, F., Gonzalez, D. and Aguilar, E. 1986. Serotonin stimulates GH secretion through a direct pituitary action: studies in hypophysectomized autografted animals and in perifused pituitaries. Acta Endocrinol. 113: 317–322.

    PubMed  Google Scholar 

  • Marchant, T.A., Chang, J.P., Nahorniak, C.S. and Peter, R.E. 1989. Evidence that gonadotropin-releasing hormone also functions as a growth hormone-releasing factor in the goldfish. Endocrinology 124: 2509–2518.

    PubMed  Google Scholar 

  • Marchant, T.A., Fraser, R.A., Andrews, P.C. and Peter, R.E. 1987. The influence of mammalian and teleost somatostatins on the secretion of growth hormone from goldfish (Carassius auratus L.) pituitary fragments in vitro. Regul. Pept. 17, 41–52.

    Article  PubMed  Google Scholar 

  • Margolis-Kazan, H., Halpern-Sebold, L. and Schreibman, M. 1985. Immunocytochemical localization of serotonin in the brain and pituitary gland of the platyfish, Xiphophorus maculatus. Cell Tiss. Res. 240: 311–314.

    Google Scholar 

  • Munoz-Acedo, G., Lopez-Sanudo, S. and Arilla, E. 1993. Effect of serotonin axon injury on the somatostinergic system in rat frontoparietal cortex. Life Sci. 52: 803–809.

    Article  PubMed  Google Scholar 

  • Murakami, T., Kato, Y., Kabayama, Y., Tojo, K., Inoue, T. and Imura, H. 1986. Involvement of growth hormone (GH)-releasing factor in GH secretion induced by serotonergic mechanisms in conscious rats. Endocrinology 119: 1089–1092.

    PubMed  Google Scholar 

  • Murthy, C.K. and Peter, R.E. 1994. Functional evidence regarding receptor subtypes mediating the actions of native gonadotropinreleasing hormone (GnRH) in goldfish, Carassius auratus. Gen. Comp. Endocrinol. 94: 78–91.

    Article  PubMed  Google Scholar 

  • Peter, R.E., Nahorniak, C.S., Chang, J.P. and Crim, L.W. 1984. Gonadotropin release from the pars distalis of goldfish, Carassius auratus, transplanted besides the brain or into brain ventricle: Additional evidence for gonadotropin-release inhibitory factor. Gen. Comp. Endocrinol. 55, 337–346.

    PubMed  Google Scholar 

  • Peter, R.E., Chang, J.P., Nahorniak, C.S., Omeljaniuk, R.J., Sokolowska, M., Shih, S.H. and Billard, R. 1986. Interactions of catecholamines and GnRH in regulation of gonadotropin secretion in teleost fish. Recent Progr. Horm. Res. 42: 513–548.

    PubMed  Google Scholar 

  • Peter, R.E., Yu, K.L., Marchant, T.A. and Rosenblum, P.M. 1990. Direct neural regulation of the teleost adenohypophysis. J. Exp. Zool. (Suppl)4: 84–89.

    Google Scholar 

  • Pinilla, L., Ranchal, A., Aguilar, R. and Aguilar, E. 1994. Role of the serotonergic system in the control of gonadotropin secretion in prepubertal male rats. Eur. J. Endocrinol. 130: 617–624.

    PubMed  Google Scholar 

  • Rodriguez, M., Feleder, C., Szwarcfarb, B., Scacchi, P., Arias, P. and Moguilevsky, J. 1994. Mediobasal hypothalamic perifusion with serotonin inhibits steroid-stimulated LH secretion: Assessment with the push-pull technique. Neuroendocrinol. Lett. 16: 121–129.

    Google Scholar 

  • Saligaut, C., Salbert, G., Bailhache, T., Bennani, S. and Jego, P. 1992. Serotonin and dopamine turnover in the female rainbow trout (Oncorhynchus mykiss) brain and pituitary: Changes during the annual reproductive cycle. Gen. Comp. Endocrinol. 85: 261–268.

    PubMed  Google Scholar 

  • Senthilkumaran, B. and Joy, K.P. 1993. Annual variations in hypothalamic serotonin and monoamine oxidase in the catfish Heteropneustes fossilis with a note on brain regional differences of day-night variations in gonadal preparatory phase. Gen. Comp. Endocrinol. 90: 372–382.

    Article  PubMed  Google Scholar 

  • Somoza, G.M. and Peter, R.E. 1991. Effects of serotonin on gonadotropin and growth hormone release from in vitro perifused goldfish pituitary fragments. Gen. Comp. Endocrinol. 82: 103–110.

    PubMed  Google Scholar 

  • Somoza, G.M., Yu, K.L. and Peter, R.E. 1988. Serotonin stimulates gonadotropin release in female and male goldfish, Carassius auratus L. Gen. Comp. Endocrinol. 72: 374–382.

    PubMed  Google Scholar 

  • Tepavcevic, D., Giljevic, Z., Korsic, M., Halimi, S., Suchanek, E., Jelic, T., Aganovic, I., Kozic, B. and Plavsic, V. 1994. Effects of ritanserin, a novel serotonin-S—2 receptor antagonist, on the secretion of pituitary hormones in normal humans. J. Endocrinol. Inves. 17: 1–5.

    Google Scholar 

  • Van der Kar, L.D. and Brownfield, M.S. 1993. serotonergic neurons and neuroendocrine function. NIPS 8: 202–207.

    Google Scholar 

  • Vitale, M.L., Parisi, M.N., Chiocchio, S.R. and Tramezzani, J.H. 1986. Serotonin induces gonadotrophin release through stimulation of LH-releasing hormone release from the median eminence. J. Endocrinol. 111: 309–315.

    PubMed  Google Scholar 

  • Wehrenberg, W.B., Wiviott, S.D., Voltz, D.M. and Giustina, A. 1992. Pyridostigmine-mediated growth hormone release: Evidence for somatostatin involvement. Endocrinology 130: 1445–1450.

    Article  PubMed  Google Scholar 

  • Whisnant, C.S. and Goodman, R.L. 1990. Further evidence that serotonin mediates the steroid-independent inhibition of luteinizing hormone secretion in anestrous ewes. Biol. Reprod. 42: 656–661

    PubMed  Google Scholar 

  • Wong, A.O.L., Chang, J.P. and Peter, R.E. 1991. Dopamine stimulates growth hormone release from the pituitary of the goldfish through dopamine D1 receptors. In Program and Abstracts, the 73rd Ann. Meeting Endocr. Soc., p. 416 (Abstract #1541).

  • Wong, A.O.L., Chang, J.P. and Peter, R.E. 1992. Dopamine stimulates growth hormone release from the pituitary of gold-fish, Carassius auratus, through the dopamine D1 receptors. Endocrinology 130, 1201–1210.

    Article  PubMed  Google Scholar 

  • Wong, A.O.L., Leung, M.Y., Murthy, C.K., Chang, J.P. and Peter, R.E. (1995). Effects of norepinephrine on growth hormone release from the pituitary of goldfish, Carassius auratus. Ann. Sci. Meeting Soc. Study of Endocrinology, Metabolism, and Reproduction. Publication No. 10, p. 5.

  • Yu, K.L., Rosenblum, P.M. and Peter, R.E. 1991. In vitro release of gonadotropin-releasing hormone from the brain preopticanterior hypothalamus region and pituitary of female goldfish. Gen. Comp. Endocrinol. 81: 256–267.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wong, A., Murphy, C., Chang, J. et al. Direct actions of serotonin on gonadotropin-II and growth hormone release from goldfish pituitary cells: interactions with gonadotropin-releasing hormone and dopamine and further evaluation of serotonin receptor specificity. Fish Physiology and Biochemistry 19, 23–34 (1998). https://doi.org/10.1023/A:1007713622603

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007713622603

Navigation