Exp Clin Endocrinol Diabetes 2003; 111(6): 335-340
DOI: 10.1055/s-2003-42723
Article

J. A. Barth Verlag in Georg Thieme Verlag Stuttgart · New York

The Role of GabaA Receptors in the Neural Systems of the Ventromedial Hypothalamus-Nucleus Infundibular Region in the Control of GnRH Release in Ewes during Follicular Phase

D. Tomaszewska-Zaremba 1 , K. Mateusiak 1 , F. Przekop 1
  • 1The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Jabłonna, Poland
Further Information

Publication History

Received: July 17, 2002 First decision: November 24, 2002

Accepted: March 3, 2003

Publication Date:
01 October 2003 (online)

Abstract

To examine the role of the GABAA receptor mediating systems in the control of gonadotropin releasing hormone (GnRH) release from the ventromedial-infundibular region (VEN/NI) of the hypothalamus of ewes during the follicular phase of the estrous cycle, the extracellular concentrations of GnRH, β-endorphin (B-END), noradrenaline (NE), dopamine (DA), and their metabolites MHPG, DOPAC and concentration of luteinizing hormone (LH) in blood plasma were quantified during local stimulation or blockade of GABAA receptors with muscimol and bicuculline, respectively. Stimulation of GABAA receptors attenuated GnRH and LH release, increased β-endorphin outflow and dopaminergic activity but had no evident effect on noradrenergic activity. Blockade of GABAA receptors decreased β-endorphin release but had no evident effect on the extracellular concentration of GnRH, LH levels in the blood and catecholaminergic activity. It is suggested that suppression of GnRH/LH release under muscimol treatment may result from activation of GABAA receptors on GnRH nerve terminals and through GABAA receptor mechanism activated β-endorphinergic and dopaminergic neurons in the VEN/NI. Lack of changes in NE and MHPG concentration during stimulation or blockade of GABAA receptors suggests, that during the follicular phase of the estrous cycle the noradrenergic system in the VEN/NI is not involved in the control of GnRH/LH release by GABA.

References

  • 1 Anderson R, Mitchell R. Effect of GABA receptor agonists on [3H] dopamine release from median eminence and pituitary neuromediate lobe.  Eur J Pharmacol. 1985;  115 109-112
  • 2 Anderson S T, Walsh J P, Tillet Y, Clarke I J, Curlevis J D. Dopaminergic input to the ventromedial hypothalamus facilitates the estrogen-induced luteinizing hormone surge in ewes.  Neuroendocrinology. 2001;  73 91-101
  • 3 Barraclough C, Wise P. The role of catecholamines in the regulation of pituitary luteinizing hormone and follicle stimulating hormone secretion.  Endocrine Rev. 1982;  3 91-119
  • 4 Bilger M, Heger S, Brann D W, Paredes A, Ojeda S R. A conditional tetracycline - regulated increase in gamma amino butyric acid production near luteinizing hormone releasing hormone nerve terminals disrups estrous cyclicity in the rat.  Endocrinology. 2001;  142 2102-2114
  • 5 Bourguignon J P, Gérard A, Purnelle G, Czajkowski V, Yamanaka C, Lemaitre M, Rigo J M, Moonen G, Franchimont P. Duality of glutamatergic and gabaergic control of pulsatile GnRH secretion by rat hypothalamic explants: I. Effects of antisense digodeoxynucleotides using explants including or excluding the preoptic area.  J Neuroendocrinology. 1997;  9 183-191
  • 6 Chomicka L K, Woliñska-Witort E, Przekop F. Release of LHRH, β-endorphin and dopamine by the nucleus infundibularis-median eminence during the estrous cycle in the ewe.  Eur J Endocrinol. 1994;  130 (Supp 2) 43
  • 7 Conover C D, Kuljis R O, Rabii J, Advis J P. Β-endorphin regulation of luteinizing hormone-releasing hormone at median eminence in ewes: immunocytochemical and physiological evidence.  Neuroendocrinology. 1993;  57 1182-1195
  • 8 Curlevis J D, Naylor A M, Rhind S M, Mc Neilly A S. Effect of beta-endorphin on pulsatile luteinizing hormone and prolactin secretion during the follicular phase in the ewe.  J Neuroendocrinol. 1991;  3 123-127
  • 9 Domański E, Chomicka L K, Ostrowska A, Gajewska A, Mateusiak K. Release of luteinizing hormone-releasing hormone, β-endorphin and noradrenaline by the nucleus infundibularis/median eminence during periovulatory period in sheep.  Neuroendocrinology. 1991;  54 151-158
  • 10 Domański E, Gajewska A, Kochman H, Masiukiewicz E, Rzeszotarska B, Kochman K. Production of antibody specific against mammalian LHRH decapeptide.  Endocrinol Pol. 1994;  45 147-153
  • 11 Donoso A O, Löpez F J, Negro-Vilar A. Cross-talk between excitatory and inhibitory amino acids in the regulation of luteinizing hormone-releasing hormone secretion.  Endocrinology. 1992;  131 1559-1561
  • 12 Feleder C, Jarry H, Leonhardt S, Wuttke W, Moguilevsky J A. The gabaergic control of gonadotropin-releasing hormone secretion in male rats during sexual maturation involves effects on hypothalamic excitatory and inhibitory amino acid systems.  Neuroendocrinology. 1996;  64 305-312
  • 13 Ferreira S A, Scott C J, Kuehl D C, Jackson G L. Differential regulation of luteinizing hormone release by γ-aminobutyric acid receptor subtypes in the arcuate-ventromedial region of the castrated ram.  Endocrinology. 1996;  137 3453-3460
  • 14 Fiber J M, Etgen A M. GABA augments basal and electrically stimulated 3H-noradrenaline release in hypothalamic, preoptic area and cortical slices of the female rats.  Neurochem Int. 1997;  3 769-780
  • 15 Fiber J M, Etgen A M. Evidence that GABA augmentation of norepinephrine release is mediated by interneurons.  Brain Res. 1998;  790 329-333
  • 16 Goodman R L, Robinson J E, Kendrick K M, Dyer R G. Is the inhibitory action of estradiol on luteinizing hormone pulse frequency in anestrous ewes mediated by noradrenergic neurons in the preoptic area?.  Neuroendocrinology. 1995;  61 284-292
  • 17 Hales T G, Sanderson M J, Charles A C. GABA has excitatory actions on GnRH-secreting immortalized hypothalamic (GT1 - 7) neurons.  Neuroendocrinology. 1994;  59 297-308
  • 18 Herbison A E, Dyer R G. Effect on luteinizing hormone secretion of GABA receptor modulation in the preoptic area of the rat brain.  Neuroendocrinology. 1991;  53 317-323
  • 19 Herbison A E. Estrogen regulation of GABA transmission in the rat preoptic area.  Brain Res Bull. 1997;  44 321-326
  • 20 Herbison A E. Multimodal influence of estrogen upon gonadotropin-releasing hormone neurons.  Endocrine Rev. 1998;  19 302-330
  • 21 Horvath T L, Naftolin F, Leranth C. Luteinizing hormone-releasing hormone and gamma-aminobutyric acid neurons in the medial preoptic area are synaptic targets of dopamine axons originating in anterior periventricular areas.  J Neuroendocrinology. 1993;  5 71-79
  • 22 Jarry H, Leonhardt S, Wuttke W. Gamma-aminobutyric acid neurons in the preoptic/anterior hypothalamic area are synchronize the phasic activity of the gonadotropin-releasing hormone pulse generator in ovariectomized rats.  Neuroendocrinology. 1991;  53 261-267
  • 23 Jarry H, Perschl A, Wuttke W. Further evidence that preoptic anterior hypothalamic GABAergic neurons are part of the GnRH pulse generator.  Acta Endocrinol. 1998;  118 573-579
  • 24 Leonhardt S, Seong J Y, Kim K, Thorun Y, Wuttke W. Activation of central GABA-A but not GABA-B receptors rapidly reduces pituitary LH release and GnRH gene expression in the preoptic/anterior hypothalamic area of ovariectomized rats.  Neuroendocrinology. 1995;  61 655-662
  • 25 Leonhardt S, Böning B, Luft H, Wuttke W, Jarry H. Activation of gene expression of the γ-aminobutyric acid rather than the glutamatergic system in the preoptic area during the preovulatory gonadotropin surge of the rat.  Neuroendocrinology. 2000;  71 8-15
  • 26 Leshin L S, Malven P V. Radioimmunoassay for β-endorphin (lipotropin) in unextracted plasma from sheep.  Domestic Animal Endocrinol. 1984;  1 175-188
  • 27 Martinez de la Escalera G, Choi A LH, Weiner R J. Biphasic gabaergic regulation of GnRH secretion in GT1 cell lines.  Neuroendocrinology. 1994;  59 420-425
  • 28 Merriam G R, Wachter K W. Algorithms for the study of episodic hormone secretion.  (Endocrinol Metab 6) Am J Physiol. 1982;  243 E310-E318
  • 29 Navarro C E, Cabrera R J, Donoso A O. Interaction between glutamate and GABA on 3H - noradrenaline release from rat hypothalamus.  Brain Res Bull. 1995;  37 119-122
  • 30 Nikolarakis K E, Loeffler J-PH, Almeida O FX, Herz A. Pre- and postsynaptic actions of GABA on the release of hypothalamic gonadotropin-releasing hormone (GnRH).  Brain Res Bull. 1988;  21 677-683
  • 31 Przekop F, Mateusiak K, Stupnicka E, Romanowicz K, Domañski E. Suppressive effect of β-endorphin on the secretion of cortisol under stress conditions in sheep.  Exp Clin Endocrinol. 1990;  95 307-314
  • 32 Robinson J E, Kendrick K M, Lambart C E. Changes in the release of gamma-aminobutyric acid and catecholamines in the preoptic/septal area prior to and during the preovulatory surge of luteinizing hormone in the ewe.  J Neuroendocrinology. 1991;  3 393-399
  • 33 Robinson J E, Kendrick K M. Inhibition of luteinizing hormone secretion in the ewe by progesterone: associated changes in the release of gamma-aminobutyric acid and noradrenaline in the preoptic area as measured by intracranial microdialysis.  J Neuroendocrinology. 1992;  4 231-236
  • 34 Robinson J E. Gamma amino-butyric acid and the control of GnRH secretion in sheep.  J Reprod Fertil Supp.. 1995;  49 221-230
  • 35 Scott C J, Clarke I J. Inhibition of luteinizing hormone secretion in ovariectomized ewes during the breeding season by γ-aminobutyric acid (GABA) is mediated by GABA-A receptors, but not GABA-B receptors.  Endocrinology. 1993 a;  132 1789-1796
  • 36 Scott C J, Clarke I J. Evidence that changes in the function of the subtypes of the receptors for γ-aminobutyric acid may be involved in the seasonal changes in the negative-feedback effects of estrogen on gonadotropin-releasing hormone secretion and plasma luteinizing hormone levels in the ewe.  Endocrinology. 1993 b;  133 2904-2912
  • 37 Sin J A, Skynner M J, Pape J R, Herbison A E. Late postnatal reorganization of GABA receptor signalling in native GnRH neurons.  Eur J Neurosci. 2000;  12 3497-3504
  • 38 Stupnicki R, Madej A. Radioimmunoassay of LH in blood plasma of farm animals.  Endokrinologie. 1976;  68 6-13
  • 39 Taniyama K, Niwa M, Kataoka Y, Yamashita K. Activation of protein kinase C suppresses the gamma-aminobutyric acid β receptor-mediated inhibition of vesicular release of noradrenaline and acetylocholine.  J Neurochem. 1992;  58 1239-1245
  • 40 Tomaszewska-Zaremba D, Przekop F, Mateusiak K. The involvement of GABAA receptors in the control of GnRH and β-endorphin release, and catecholaminergic activity in the ventromedial-infundibular region of hypothalamus in anestrous ewes.  J Physiol Pharmacol. 2001;  52 489-500
  • 41 Traczyk W, Przekop F. Methods of investigation of the function of the hypothalamus and hypophysis in chronic experiments in sheep.  Acta Physiol Pol. 1963;  14 217-226
  • 42 Viguie C, Caraty A, Locatelli A, Malpaux B. Regulation of luteinizing hormone-releasing hormone (LHRH) secretion by melatonin in the ewe. Simultaneous delayed increase in LHRH and luteininzing hormone pulse secretion.  Biol Reprod. 1995;  52 1114-1120
  • 43 Wagner E J, Goudreau J L, Moore K E, Lookingland K J. GABAergic regulation of tuberoinfundibular dopaminergic neurons in the male rat.  Brain Res. 1994;  659 194-200
  • 44 Welento J, Steyn S, Milart Z. Observation on the stereotaxic configuration of the hypothalamus nuclei in sheep.  Anat Anz. 1969;  124 1-27

Ph. D. D. Tomaszewska-Zaremba

Polish Academy of Sciences
The Kielanowski Institute of Animal Physiology and Nutrition

05-110 Jabłonna

Poland

Phone: + 48227824422

Fax: + 48 2 27 74 20 38

Email: d_tomaszewska@poczta.onet.pl