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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Jan 4;91(1):395–399. doi: 10.1073/pnas.91.1.395

gamma-Aminobutyric acid is an inhibitory neurotransmitter restricting the release of luteinizing hormone-releasing hormone before the onset of puberty.

D Mitsushima 1, D L Hei 1, E Terasawa 1
PMCID: PMC42954  PMID: 8278400

Abstract

To test the hypothesis that the pubertal increase in luteinizing hormone-releasing hormone (LHRH) release is withheld by a dominant inhibitory neuronal system, the role of gamma-aminobutyric acid (GABA), a known inhibitory neurotransmitter, in the control of LHRH release was examined in conscious female monkeys at the prepubertal and pubertal stages using a push-pull perfusion method. GABA, bicuculline (a GABAA receptor blocker), and 2-hydroxysaclofen (a GABAB receptor blocker) were directly infused into the stalk-median eminence while perfusates were collected for LHRH determination. Bicuculline, but not saclofen, induced a large and prompt increase in LHRH release in prepubertal monkeys, whereas it stimulated LHRH release slightly in pubertal monkeys. In contrast, GABA suppressed LHRH release in pubertal, but not prepubertal, monkeys. These differential effects of GABA and the GABA antagonist on LHRH release in the two developmental stages were due to an age factor rather than to the steroid hormonal background. Moreover, GABA release in the stalk-median eminence of prepubertal monkeys was much higher than that in pubertal monkeys. Thus, the results suggest that in the prepubertal period there is a powerful GABA inhibition of the LHRH neurosecretory system: infusions of GABAA, but not GABAB, antagonists stimulate LHRH release by removal of the endogenous GABA inhibition, whereas exogenous GABA is ineffective because of high endogenous GABA levels. The decrease of this tonic inhibition may be a key factor for the onset of puberty in non-human primates.

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Selected References

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  1. Akema T., Chiba A., Kimura F. On the relationship between noradrenergic stimulatory and GABAergic inhibitory systems in the control of luteinizing hormone secretion in female rats. Neuroendocrinology. 1990 Dec;52(6):566–572. doi: 10.1159/000125645. [DOI] [PubMed] [Google Scholar]
  2. Benson D. L., Isackson P. J., Hendry S. H., Jones E. G. Differential gene expression for glutamic acid decarboxylase and type II calcium-calmodulin-dependent protein kinase in basal ganglia, thalamus, and hypothalamus of the monkey. J Neurosci. 1991 Jun;11(6):1540–1564. doi: 10.1523/JNEUROSCI.11-06-01540.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bourdelais A., Kalivas P. W. High sensitivity HPLC assay for GABA in brain dialysis studies. J Neurosci Methods. 1991 Sep;39(2):115–121. doi: 10.1016/0165-0270(91)90077-d. [DOI] [PubMed] [Google Scholar]
  4. Chongthammakun S., Claypool L. E., Terasawa E. Ovariectomy increases in vivo luteinizing hormone-releasing hormone release in pubertal, but not prepubertal, female rhesus monkeys. J Neuroendocrinol. 1993 Feb;5(1):41–50. doi: 10.1111/j.1365-2826.1993.tb00362.x. [DOI] [PubMed] [Google Scholar]
  5. Chongthammakun S., Terasawa E. Negative feedback effects of estrogen on luteinizing hormone-releasing hormone release occur in pubertal, but not prepubertal, ovariectomized female rhesus monkeys. Endocrinology. 1993 Feb;132(2):735–743. doi: 10.1210/endo.132.2.8425492. [DOI] [PubMed] [Google Scholar]
  6. Claypool L. E., Watanabe G., Terasawa E. Effects of electrical stimulation of the medial basal hypothalamus on the in vivo release of luteinizing hormone-releasing hormone in the prepubertal and peripubertal female monkey. Endocrinology. 1990 Dec;127(6):3014–3022. doi: 10.1210/endo-127-6-3014. [DOI] [PubMed] [Google Scholar]
  7. Conte F. A., Grumbach M. M., Kaplan S. L., Reiter E. O. Correlation of luteinizing hormone-releasing factor-induced luteinizing hormone and follicle-stimulating hormone release from infancy to 19 years with the changing pattern of gonadotropin secretion in agonadal patients: relation to the restraint of puberty. J Clin Endocrinol Metab. 1980 Jan;50(1):163–168. doi: 10.1210/jcem-50-1-163. [DOI] [PubMed] [Google Scholar]
  8. Fuchs E., Mansky T., Stock K. W., Vijayan E., Wuttke W. Involvement of catecholamines and glutamate in GABAergic mechanism regulatory to luteinizing hormone and prolactin secretion. Neuroendocrinology. 1984 Jun;38(6):484–489. doi: 10.1159/000123937. [DOI] [PubMed] [Google Scholar]
  9. Gay V. L., Plant T. M. N-methyl-D,L-aspartate elicits hypothalamic gonadotropin-releasing hormone release in prepubertal male rhesus monkeys (Macaca mulatta). Endocrinology. 1987 Jun;120(6):2289–2296. doi: 10.1210/endo-120-6-2289. [DOI] [PubMed] [Google Scholar]
  10. Gearing M., Terasawa E. Luteinizing hormone releasing hormone (LHRH) neuroterminals mapped using the push-pull perfusion method in the rhesus monkey. Brain Res Bull. 1988 Jul;21(1):117–121. doi: 10.1016/0361-9230(88)90126-8. [DOI] [PubMed] [Google Scholar]
  11. Gore A. C., Mitsushima D., Terasawa E. A possible role of neuropeptide Y in the control of the onset of puberty in female rhesus monkeys. Neuroendocrinology. 1993 Jul;58(1):23–34. doi: 10.1159/000126508. [DOI] [PubMed] [Google Scholar]
  12. Gore A. C., Terasawa E. A role for norepinephrine in the control of puberty in the female rhesus monkey, Macaca mulatta. Endocrinology. 1991 Dec;129(6):3009–3017. doi: 10.1210/endo-129-6-3009. [DOI] [PubMed] [Google Scholar]
  13. Jarry H., Leonhardt S., Wuttke W. Gamma-aminobutyric acid neurons in the preoptic/anterior hypothalamic area synchronize the phasic activity of the gonadotropin-releasing hormone pulse generator in ovariectomized rats. Neuroendocrinology. 1991 Mar;53(3):261–267. doi: 10.1159/000125727. [DOI] [PubMed] [Google Scholar]
  14. Leranth C., MacLusky N. J., Sakamoto H., Shanabrough M., Naftolin F. Glutamic acid decarboxylase-containing axons synapse on LHRH neurons in the rat medial preoptic area. Neuroendocrinology. 1985 Jun;40(6):536–539. doi: 10.1159/000124127. [DOI] [PubMed] [Google Scholar]
  15. Masotto C., Negro-Vilar A. Activation of gamma-aminobutyric acid B-receptors abolishes naloxone-stimulated luteinizing hormone release. Endocrinology. 1987 Dec;121(6):2251–2255. doi: 10.1210/endo-121-6-2251. [DOI] [PubMed] [Google Scholar]
  16. Plant T. M. A study of the role of the postnatal testes in determining the ontogeny of gonadotropin secretion in the male rhesus monkey (Macaca mulatta). Endocrinology. 1985 Apr;116(4):1341–1350. doi: 10.1210/endo-116-4-1341. [DOI] [PubMed] [Google Scholar]
  17. Plant T. M., Gay V. L., Marshall G. R., Arslan M. Puberty in monkeys is triggered by chemical stimulation of the hypothalamus. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2506–2510. doi: 10.1073/pnas.86.7.2506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Reiter E. O., Grumbach M. M. Neuroendocrine control mechanisms and the onset of puberty. Annu Rev Physiol. 1982;44:595–613. doi: 10.1146/annurev.ph.44.030182.003115. [DOI] [PubMed] [Google Scholar]
  19. Silverman A. J., Antunes J. L., Abrams G. M., Nilaver G., Thau R., Robinson J. A., Ferin M., Krey L. C. The luteinizing hormone-releasing hormone pathways in rhesus (Macaca mulatta) and pigtailed (Macaca nemestrina) monkeys: new observations on thick, unembedded sections. J Comp Neurol. 1982 Nov 1;211(3):309–317. doi: 10.1002/cne.902110309. [DOI] [PubMed] [Google Scholar]
  20. Terasawa E., Bridson W. E., Nass T. E., Noonan J. J., Dierschke D. J. Developmental changes in the luteinizing hormone secretory pattern in peripubertal female rhesus monkeys: comparisons between gonadally intact and ovariectomized animals. Endocrinology. 1984 Dec;115(6):2233–2240. doi: 10.1210/endo-115-6-2233. [DOI] [PubMed] [Google Scholar]
  21. Terasawa E., Krook C., Hei D. L., Gearing M., Schultz N. J., Davis G. A. Norepinephrine is a possible neurotransmitter stimulating pulsatile release of luteinizing hormone-releasing hormone in the rhesus monkey. Endocrinology. 1988 Oct;123(4):1808–1816. doi: 10.1210/endo-123-4-1808. [DOI] [PubMed] [Google Scholar]
  22. Terasawa E., Noonan J. J., Nass T. E., Loose M. D. Posterior hypothalamic lesions advance the onset of puberty in the female rhesus monkey. Endocrinology. 1984 Dec;115(6):2241–2250. doi: 10.1210/endo-115-6-2241. [DOI] [PubMed] [Google Scholar]
  23. Thind K. K., Goldsmith P. C. GABAergic and catecholaminergic synaptic interactions in the macaque hypothalamus: double label immunostaining with peroxidase-antiperoxidase and colloidal gold. Brain Res. 1986 Sep 24;383(1-2):215–227. doi: 10.1016/0006-8993(86)90021-1. [DOI] [PubMed] [Google Scholar]
  24. Urbanski H. F., Ojeda S. R. Activation of luteinizing hormone-releasing hormone release advances the onset of female puberty. Neuroendocrinology. 1987 Sep;46(3):273–276. doi: 10.1159/000124831. [DOI] [PubMed] [Google Scholar]
  25. Watanabe G., Terasawa E. In vivo release of luteinizing hormone releasing hormone increases with puberty in the female rhesus monkey. Endocrinology. 1989 Jul;125(1):92–99. doi: 10.1210/endo-125-1-92. [DOI] [PubMed] [Google Scholar]
  26. Wildt L., Marshall G., Knobil E. Experimental induction of puberty in the infantile female rhesus monkey. Science. 1980 Mar 21;207(4437):1373–1375. doi: 10.1126/science.6986658. [DOI] [PubMed] [Google Scholar]
  27. Winter J. S., Faiman C. Serum gonadotropin in concentrations in agonadal children and adults. J Clin Endocrinol Metab. 1972 Oct;35(4):561–564. doi: 10.1210/jcem-35-4-561. [DOI] [PubMed] [Google Scholar]
  28. Woller M. J., McDonald J. K., Reboussin D. M., Terasawa E. Neuropeptide Y is a neuromodulator of pulsatile luteinizing hormone-releasing hormone release in the gonadectomized rhesus monkey. Endocrinology. 1992 Apr;130(4):2333–2342. doi: 10.1210/endo.130.4.1547745. [DOI] [PubMed] [Google Scholar]
  29. Zhang S. J., Jackson M. B. GABA-activated chloride channels in secretory nerve endings. Science. 1993 Jan 22;259(5094):531–534. doi: 10.1126/science.8380942. [DOI] [PubMed] [Google Scholar]

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