The potential role of the neurotransmitter γ-aminobutyric acid (GABA) in the control of the secretion of the two pituitary fish gonadotropins (GTH-1 and GTH-2) was investigated in male and female rainbow trout (Oncorhynchus mykiss). The presence of glutamate decarboxylase-positive fibers in the neurohypophyseal digitations adjacent to the gonadotropic cells was demonstrated by means of double immunohistochemistry, providing a morphofunctional support for potential GABA-gonadotropin interactions in both sexes. In spermiating males, in vivo treatment with GABA did not affect basal gonadotropin release, but stimulated GTH-1 release when coadministered with a gonadotropin-releasing hormone analogue (GnRHa), and potentiated GnRHa-stimulated GTH-2 release. In vitro, using dispersed pituitary cells, GABA stimulated basal GTH-1 and GTH-2 secretion, in a dose-dependent manner, and potentiated salmon GnRH effect on both hormones. In mature females, GABA induced in vivo a strong elevation of plasma GTH-2 levels after 2– 6 h of injection, but had no effect in vitro. GABA treatment in vivo was also stimulatory in recrudescent females, slightly increasing plasma GTH-2 levels in both saline- and GnRHa-treated fish (GnRHa alone has no effect at this stage). Immature fish were unresponsive to GABA/GnRHa treatments but, after steroid implantation [testosterone (T) or estradiol] for 13 days, injection of GABA stimulated GTH-2 release in vivo (also GTH-1 slightly in T-implanted fish). In conclusion, GABA has an overall stimulatory action on GTH-1 and GTH-2 secretion in rainbow trout, which depends on the sex and the reproductive stage of the fish. The stimulatory action of GABA might be exerted, at least in part, directly onto the gonadotropes, as it stimulates basal and GnRH-induced GTH-1 and GTH-2 secretion from dispersed pituitary cells.

Keywords:
=γ-Aminobutyric acid, Glutamate decarboxylase, Gonadotropins, Reproduction, Fish
1.
Wagner S, Castel M, Gainer H, Yarom Y: GABA in the mammalian suprachiasmatic nucleus and its role in diurnal rhythmicity. Nature 1997;387:598–603.
2.
Mugnaini E, Oertel WG: An atlas of the distribution of GABAergic neurons and terminals in the rat CNS as revealed by GAD immunohistochemistry; in Björklund A, Hökfelt T (eds): Handbook of Chemical Neuroanatomy. Amsterdam, Elsevier, 1985, vol 4, pp 436–622.
3.
Decavel C, van den Pol AN: GABA: A dominant neurotransmitter in the hypothalamus. J Comp Neurol 1990;302:1019–1037.
4.
Tillakaratne NJK, Tobin AJ, Houser CR: Comparative localization of mRNAs encoding two forms of glutamic acid decarboxylase with nonradioactive in situ hybridization methods. J Comp Neurol 1993;331:339–362.
5.
McCarthy MM, Kaufman LC, Brooks PJ, Pfaff DW, Schwartz-Giblin S: Estrogen modulation of mRNA levels for the two forms of glutamic acid decarboxylase (GAD) in female rat brain. J Comp Neurol 1995;360:685–697.
6.
McCann SM, Vijayan E, Negro-Vilar A, Mizunuma H, Mangat H: Gamma-aminobutyric acid (GABA), a modulator of anterior pituitary hormone secretion by hypothalamic and pituitary action. Psychoneuroendocrinology 1984;9:97–106.
7.
Donoso AO, Seltzer AM, Navarro CE, Cabrera RJ, Lopez FJ, Negro-Vilar A: Regulation of luteinizing hormone-releasing hormone and luteinizing hormone secretion by hypothalamic amino-acids. Braz J Med Biol Res 1994;27:921–932.
8.
McCann SM, Rettori V: The role of gamma-aminobutyric acid in the control of anterior pituitary hormone secretion; in Squires RF (ed): Gaba and Benzodiazepin Receptors. Boca Raton, CRC Press, 1988, vol 1, pp 123–134.
9.
Virmani MA, Stojilkovic SS, Catt KJ: Stimulation of luteinizing hormone release by γ-aminobutyric acid (GABA) agonists: Mediation by GABAA-type receptors and activation of chloride and voltage sensitive calcium channels. Endocrinology 1990;126:2499–2505.
10.
Flugge G, Oertel WH, Wuttke W: Evidence for estrogen receptive GABAergic neurons in the preoptic/anterior hypothalamic area of the rat brain. Neuroendocrinology 1986;43:1–5.
11.
Herbison AE, Robinson JE, Skinner DC: Distribution of estrogen receptor-immunoreactive cells in the preoptic area of the ewe: Co-localization with glutamic acid decarboxylase but not luteinizing hormone-releasing hormone. Neuroendocrinology 1993;57:751–759.
12.
Leranth CS, Mac Lusky NJ, Sakamoto H, Shanabrough M, Naftolin F: Glutamic acid decarboxylase-containing axons synapse on LR-RH neurons in the rat medial preoptic area. Neuroendocrinology 1985;40:536–539.
13.
Kah O, Anglade I, Leprêtre E, Dubourg P, de Monbrison D: The reproductive brain in fish. Fish Physiol Biochem 1993;11:85–98.
14.
Trudeau VL: Neuroendocrine regulation of gonadotrophin II release and gonadal growth in the goldfish, Carassius auratus. Rev Reprod 1997;2:55–68.
15.
Kah O, Trudeau VL, Sloley BD, Chang JP, Dubourg P, Yu KL, Peter RE: Influence of GABA on gonadotropin release in the goldfish. Neuroendocrinology 1992;55:396–404.
16.
Trudeau VL, Sloley BD, Peter RE: Testosterone enhances GABA and taurine but not N-methyl-D-L-aspartate stimulation of gonadotropin secretion in the goldfish: Possible sex steroid feedback mechanisms. J Neuroendocrinol 1993;5:129–136.
17.
Trudeau VL, Sloley BD, Peter RE: GABA stimulation of gonadotropin secretion in the goldfish: Involvement of GABAA receptors, dopamine, and sex steroids. Am J Physiol 1993;265:R348–R355.
18.
Kah O, Dubourg P, Martinoli MG, Rabhi M, Gonnet F, Geffard M, Calas A: Central GABAergic innervation of the pituitary in goldfish: An autoradiographic and immunocytochemical study at the electron microscope level. Gen Comp Endocrinol 1987;67:324–332.
19.
Kawauchi H, Suzuki K, Itoh H, Swanson P, Naito N, Nagahama Y, Nozaki M, Nakai Y, Itoh S: The duality of teleost gonadotropins. Fish Physiol Biochem 1989;7:29–38.
20.
Swanson P: Salmon gonadotropins: Reconciling old and new ideas; in Scott AP, Sumpter JP, Kime DE, Rolfe MS (eds): Reproductive Physiology of Fish: Proceeding of the Fourth International Symposium, Sheffield, 1991, pp 2–7.
21.
Quérat B: Molecular evolution of the glycoprotein hormones in vertebrates; in Favey KG, Peter RE, Tobe SS (eds): Perspectives in Comparative Endocrinology. Ottawa, National Research Council of Canada, 1994, pp 27–35.
22.
Naito N, Hyodo S, Okumoto N, Urano A, Nakai Y: Differential production and regulation of gonadotropins (GTH I and GTH II) in the pituitary gland of rainbow trout, Oncorhynchus mykiss, during ovarian development. Cell Tissue Res 1991;266:457–467.
23.
Prat F, Sumpter JP, Tyler CR: Validation of radioimmunoassays for two salmon gonadotropin (GtH I and GtH II) and their plasma concentrations throughout the reproductive cycle in male and female rainbow trout (Oncorhynchus mykiss). Biol Reprod 1996;54:1375–1382.
24.
Govoroun MS, Huet JC, Pernollet JC, Breton B: Use of immobilized metal ion affinity chromatography and dye-ligand chromatography for the separation and purification of rainbow trout pituitary gonadotropins, GTH I and GTH II. J Chromatogr 1997;698:35–46.
25.
Shu S, Ju G, Fan L: The glucose oxidase-DAB-nickel method in peroxidase histochemistry of the nervous system. Neurosci Lett 1988;85:169–171.
26.
Khan IA, Thomas P: Neuroendocrine control of gonadotropin II release in the Atlantic croaker: Involvement of gamma-aminobutyric acid; in Goetz FW, Thomas P (eds): Reproductive Physiology of Fish: Proceeding of the Fifth International Symposium, Austin, Tex., 1995, p 73.
27.
Médina M, Reperant J, Dufour S, Ward R, Le Belle N, Miceli D: The distribution of GABA-immunoreactive neurons in the brain of the silver eel (Anguilla anguilla L.). Anat Embryol (Berl) 1994;189:25–39.
28.
Peter RE, Yu KL, Marchant TA, Rosenblum PM: Direct neural regulation of the teleost adenohypophysis. J Exp Zool 1990;4:84–89.
29.
Navas JM, Anglade I, Bailhache T, Pakdel F, Breton B, Jégo P, Kah O: Do gonadotrophin-releasing hormone neurons express estrogen receptors in the rainbow trout? A double immunohistochemical study. J Comp Neurol 1995;363:461–474.
30.
Erlander MG, Tillakaratne NJK, Feldblum S: Patel N, Tobin AJ: Two genes encode distinct glutamate decarboxylases. Neuron 1991;7:91–100.
31.
Bu DF, Erlander M, Hiltz BC, Tillakaratne NJK, Kaufman DL, Wagner-Mc Pherson CB, Evan GA, Tobin AJ: Two human glutamate decarboxylases, 65 kDa GAD and 67 kDa GAD, are each encoded by a single gene. Proc Natl Acad Sci USA 1992;89:2115–2119.
32.
Anglade I, Zandbergen AM, Kah O: Origin of the pituitary innervation in the goldfish. Cell Tissue Res 1993;273:345–355.
33.
Holmqvist BI, Ekström P: Hypophysiotrophic systems in the brain of the Atlantic salmon: Neuronal innervation of the pituitary and the origin of pituitary dopamine and nonapeptides identified by means of combined carbocyanine tract tracing and immunocytochemistry. J Chem Neuroanat 1995;8:122–145.
34.
Scott AP, Sumpter JP, Hardiman PA: Hormone changes during ovulation in the rainbow trout. Gen Comp Endocrinol 1983;49:128–134.
35.
Fostier A, Jalabert B, Billard R, Breton B, Zohar Y: The gonadal steroids; in Hoar WS, Randal DJ (eds): Fish Physiology. New York, Academic Press, 1983, vol 9A, pp 277–372.
36.
Linard B: Sécretion d’hormone gonadotrope et rétrocontrôles stéroïdiens chez la truite arc-en-ciel (Oncorhynchus mykiss): rôle des systèmes catécholaminergiques centraux; PhD thesis, University of Rennes 1, 1996, No 1444, pp 1–119.
37.
Linard B, Bennani S, Saligaut C: Involvement of estradiol in a catecholamine inhibitory tone of gonadotropin release in the rainbow trout (Oncorhynchus mykiss). Gen Comp Endocrinol 1995;99:192–196.
38.
Linard B, Anglade I, Navas JM, Corio M, Jego P, Saligaut C, Kah O: Coexistence of tyrosine hydroxylase- and estrogen receptor-immunoreactivity in a subset of neurons in the preoptic region of the rainbow trout. Neuroendocrinology 1996;63:156–165.
39.
Saligaut C, Linard B, Kah O, Breton B, Govorun M: Release of pituitary gonadotrophins GtH I and GtH II in the rainbow trout: Modulation by estradiol and catecholamines. Gen Comp Endocrinol 1998;109:302–309.
40.
Brustle O, Pilgrim C, Gaymann W, Reisert I: Abundant GABAergic innervation of rat posterior pituitary revealed by inhibition of GABA-transaminase. Cell Tissue Res 1988;251:59–64.
41.
Sloley BD, Kah O, Trudeau VL, Dulka JG, Peter RE: Amino acid neurotransmitter and dopamine in brain and pituitary of the goldfish: Involvement in the regulation of gonadotropin secretion. J Neurochem 1992;58:2254–2262.
42.
Sloley BD, Trudeau VL, D’Antonio M, Peter RE: Persistent elevation of tissue GABA and serum gonadotropin concentrations by GABA transaminase inhibition in goldfish. Endocr J 1994;2:385–391.
43.
Roelants I, Epler P, Mikolojczyk T, Breton B, Bieniarz K, Ollevier F: A presumptive role for GABA in the stimulatory effects of desGly10, (D-Ala6)-LHRH-ethylamide and pimozide on the gonadotropin release in carp. Life Sci 1990;47:1801–1812.
44.
Mollard P, Kah O: Cytosolic free calcium responses to GnRH in individual gonadotrophs from the goldfish pituitary. Cell Calcium 1996;20:415–424.
45.
Blazquez M, Bosma PT, Chang JP, Docherty V, Trudeau VL: γ-Aminobutyric acid upregulates the expression of a novel secretogranin-II mRNA in the goldfish pituitary. Endocrinology, in press.
46.
Fischer-Colbrie R, Laslop A, Kirchmair R: Secretogranin II: Molecular properties, regulation of biosynthesis and processing to the neuropeptide secretoneurin. Prog Neurobiol 1995;46:49–70.
47.
Fraser EJ, Blázquez M, Yoshiura Y, Kobayashi M, Docherty K, Trudeau VL: Regulation of GTH-IIβ mRNA expression in the pituitary by temperature, GnRH and GABA; in Proceedings of the 19th Conference of European Comparative Endocrinologists, Nijmegen, 1998, p 24.
48.
Wuttke W, Jarry H, Flugge G: GABA is a neurotransmitter of estrogen-receptive neurons in the central nervous system; in McCann SM, Weiner R (eds): Integrative Neuroendocrinology: Molecular, Cellular and Clinical Aspects. Basel, Karger, 1987, pp 70–79.
49.
Thind KK, Goldsmith PC: Expression of estrogen receptors in glutamate and GABA neurons of the pubertal female monkey hypothalamus. Neuroendocrinology 1997;65:314–324.
50.
Nielson DA, Shapiro DJ: Insights into hormonal control of messenger RNA stability. Mol Endocrinol 1990;4:953–957.
1999
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.