Skip to main content
Proceedings of the Royal Society B: Biological Sciences logoLink to Proceedings of the Royal Society B: Biological Sciences
. 1998 Oct 7;265(1408):1853–1859. doi: 10.1098/rspb.1998.0512

Hormone-dependent regulation of GABAA receptor gamma subunit mRNAs in sexually dimorphic regions of the rat brain.

A S Clark 1, M Myers 1, S Robinson 1, P Chang 1, L P Henderson 1
PMCID: PMC1689368  PMID: 9802242

Abstract

Transmission mediated by gamma-aminobutyric acid type A (GABAA) receptors expressed within the medial preoptic area (mPOA) and the ventromedial nucleus (VMN) of the hypothalamus is known to play critical, but contrasting, roles in regulating steroid-dependent sexual behaviours in rats. Previous studies have demonstrated a striking dichotomy in receptor composition between the two regions with regard to gamma, but not alpha or beta, subunit expression. To test if gonadal steroids regulate the expression of the gamma subunit genes within the mPOA and the VMN, in situ hybridization analysis for messenger RNAs encoding the gamma 1, gamma 2Short (gamma 2S) and gamma 2Long (gamma 2L) subunits was done in gonadectomized male and female rats and in gonadally intact females over the oestrous cycle. No significant differences in the expression of the gamma subunit mRNAs were observed in gonadectomized male versus female rats. Significant effects of gonadal state in female rats were observed for gamma 1 mRNA levels in the mPOA and gamma 2L levels in the VMN. These data demonstrate that gonadal hormones exert activational control of expression of GABAA receptor gamma subunit mRNAs and suggest that differences in receptor structure may contribute to the functional modulation of female sexual behaviours mediated by GABAergic transmission in these regions.

Full Text

The Full Text of this article is available as a PDF (314.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Araki T., Kiyama H., Maeno H., Tohyama M. Differential immunocytochemical localization of GABAA receptor gamma 1 and gamma 2 subunits in the rat brain. Brain Res Mol Brain Res. 1993 Nov;20(3):263–266. doi: 10.1016/0169-328x(93)90050-y. [DOI] [PubMed] [Google Scholar]
  2. Araki T., Kiyama H., Tohyama M. The GABAA receptor gamma 1 subunit is expressed by distinct neuronal populations. Brain Res Mol Brain Res. 1992 Sep;15(1-2):121–132. doi: 10.1016/0169-328x(92)90159-9. [DOI] [PubMed] [Google Scholar]
  3. Brussaard A. B., Kits K. S., Baker R. E., Willems W. P., Leyting-Vermeulen J. W., Voorn P., Smit A. B., Bicknell R. J., Herbison A. E. Plasticity in fast synaptic inhibition of adult oxytocin neurons caused by switch in GABA(A) receptor subunit expression. Neuron. 1997 Nov;19(5):1103–1114. doi: 10.1016/s0896-6273(00)80401-8. [DOI] [PubMed] [Google Scholar]
  4. Fernández-Guasti A., Larsson K., Beyer C. GABAergic control of masculine sexual behavior. Pharmacol Biochem Behav. 1986 Apr;24(4):1065–1070. doi: 10.1016/0091-3057(86)90456-9. [DOI] [PubMed] [Google Scholar]
  5. Fernández-Guasti A., Picazo O. The actions of diazepam and serotonergic anxiolytics vary according to the gender and the estrous cycle phase. Pharmacol Biochem Behav. 1990 Sep;37(1):77–81. doi: 10.1016/0091-3057(90)90044-i. [DOI] [PubMed] [Google Scholar]
  6. Frye C. A., Duncan J. E., Basham M., Erskine M. S. Behavioral effects of 3 alpha-androstanediol. II: Hypothalamic and preoptic area actions via a GABAergic mechanism. Behav Brain Res. 1996 Sep;79(1-2):119–130. doi: 10.1016/0166-4328(96)00005-8. [DOI] [PubMed] [Google Scholar]
  7. Frye C. A., Van Keuren K. R., Erskine M. S. Behavioral effects of 3 alpha-androstanediol. I: Modulation of sexual receptivity and promotion of GABA-stimulated chloride flux. Behav Brain Res. 1996 Sep;79(1-2):109–118. doi: 10.1016/0166-4328(96)00004-6. [DOI] [PubMed] [Google Scholar]
  8. Fénelon V. S., Herbison A. E. Plasticity in GABAA receptor subunit mRNA expression by hypothalamic magnocellular neurons in the adult rat. J Neurosci. 1996 Aug 15;16(16):4872–4880. doi: 10.1523/JNEUROSCI.16-16-04872.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gorski R. A., Gordon J. H., Shryne J. E., Southam A. M. Evidence for a morphological sex difference within the medial preoptic area of the rat brain. Brain Res. 1978 Jun 16;148(2):333–346. doi: 10.1016/0006-8993(78)90723-0. [DOI] [PubMed] [Google Scholar]
  10. Herbison A. E., Augood S. J., Simonian S. X., Chapman C. Regulation of GABA transporter activity and mRNA expression by estrogen in rat preoptic area. J Neurosci. 1995 Dec;15(12):8302–8309. doi: 10.1523/JNEUROSCI.15-12-08302.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Herbison A. E. Estrogen regulation of GABA transmission in rat preoptic area. Brain Res Bull. 1997;44(4):321–326. doi: 10.1016/s0361-9230(97)00210-4. [DOI] [PubMed] [Google Scholar]
  12. Herbison A. E., Fénelon V. S. Estrogen regulation of GABAA receptor subunit mRNA expression in preoptic area and bed nucleus of the stria terminalis of female rat brain. J Neurosci. 1995 Mar;15(3 Pt 2):2328–2337. doi: 10.1523/JNEUROSCI.15-03-02328.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Huntsman M. M., Isackson P. J., Jones E. G. Lamina-specific expression and activity-dependent regulation of seven GABAA receptor subunit mRNAs in monkey visual cortex. J Neurosci. 1994 Apr;14(4):2236–2259. doi: 10.1523/JNEUROSCI.14-04-02236.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kow L. M., Mobbs C. V., Pfaff D. W. Roles of second-messenger systems and neuronal activity in the regulation of lordosis by neurotransmitters, neuropeptides, and estrogen: a review. Neurosci Biobehav Rev. 1994 Summer;18(2):251–268. doi: 10.1016/0149-7634(94)90028-0. [DOI] [PubMed] [Google Scholar]
  15. MacLusky N. J., Bowlby D. A., Brown T. J., Peterson R. E., Hochberg R. B. Sex and the developing brain: suppression of neuronal estrogen sensitivity by developmental androgen exposure. Neurochem Res. 1997 Nov;22(11):1395–1414. doi: 10.1023/a:1022027408234. [DOI] [PubMed] [Google Scholar]
  16. Madeira M. D., Lieberman A. R. Sexual dimorphism in the mammalian limbic system. Prog Neurobiol. 1995 Mar;45(4):275–333. doi: 10.1016/0301-0082(94)00052-j. [DOI] [PubMed] [Google Scholar]
  17. Majewska M. D. Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance. Prog Neurobiol. 1992;38(4):379–395. doi: 10.1016/0301-0082(92)90025-a. [DOI] [PubMed] [Google Scholar]
  18. McCarthy M. M., Felzenberg E., Robbins A., Pfaff D. W., Schwartz-Giblin S. Infusions of diazepam and allopregnanolone into the midbrain central gray facilitate open-field behavior and sexual receptivity in female rats. Horm Behav. 1995 Sep;29(3):279–295. doi: 10.1006/hbeh.1995.1020. [DOI] [PubMed] [Google Scholar]
  19. McCarthy M. M. Frank A. Beach Award. Functional significance of steroid modulation of GABAergic neurotransmission: analysis at the behavioral, cellular, and molecular levels. Horm Behav. 1995 Jun;29(2):131–140. doi: 10.1006/hbeh.1995.1010. [DOI] [PubMed] [Google Scholar]
  20. McEwen B. S. Steroid hormones: effect on brain development and function. Horm Res. 1992;37 (Suppl 3):1–10. doi: 10.1159/000182393. [DOI] [PubMed] [Google Scholar]
  21. McGinnis M. Y., Williams G. W., Lumia A. R. Inhibition of male sex behavior by androgen receptor blockade in preoptic area or hypothalamus, but not amygdala or septum. Physiol Behav. 1996 Sep;60(3):783–789. doi: 10.1016/0031-9384(96)00088-1. [DOI] [PubMed] [Google Scholar]
  22. Miralles C. P., Gutiérrez A., Khan Z. U., Vitorica J., De Blas A. L. Differential expression of the short and long forms of the gamma 2 subunit of the GABAA/benzodiazepine receptors. Brain Res Mol Brain Res. 1994 Jul;24(1-4):129–139. doi: 10.1016/0169-328x(94)90124-4. [DOI] [PubMed] [Google Scholar]
  23. O'Connor L. H., Nock B., McEwen B. S. Regional specificity of gamma-aminobutyric acid receptor regulation by estradiol. Neuroendocrinology. 1988 Jun;47(6):473–481. doi: 10.1159/000124958. [DOI] [PubMed] [Google Scholar]
  24. Orchinik M., Weiland N. G., McEwen B. S. Chronic exposure to stress levels of corticosterone alters GABAA receptor subunit mRNA levels in rat hippocampus. Brain Res Mol Brain Res. 1995 Dec 1;34(1):29–37. doi: 10.1016/0169-328x(95)00118-c. [DOI] [PubMed] [Google Scholar]
  25. Pfaff D., Keiner M. Atlas of estradiol-concentrating cells in the central nervous system of the female rat. J Comp Neurol. 1973 Sep 15;151(2):121–158. doi: 10.1002/cne.901510204. [DOI] [PubMed] [Google Scholar]
  26. Schumacher M., Coirini H., McEwen B. S. Regulation of high-affinity GABAa receptors in specific brain regions by ovarian hormones. Neuroendocrinology. 1989 Sep;50(3):315–320. doi: 10.1159/000125239. [DOI] [PubMed] [Google Scholar]
  27. Shivers B. D., Killisch I., Sprengel R., Sontheimer H., Köhler M., Schofield P. R., Seeburg P. H. Two novel GABAA receptor subunits exist in distinct neuronal subpopulations. Neuron. 1989 Sep;3(3):327–337. doi: 10.1016/0896-6273(89)90257-2. [DOI] [PubMed] [Google Scholar]
  28. Sieghart W. Structure and pharmacology of gamma-aminobutyric acidA receptor subtypes. Pharmacol Rev. 1995 Jun;47(2):181–234. [PubMed] [Google Scholar]
  29. Simerly R. B., Chang C., Muramatsu M., Swanson L. W. Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: an in situ hybridization study. J Comp Neurol. 1990 Apr 1;294(1):76–95. doi: 10.1002/cne.902940107. [DOI] [PubMed] [Google Scholar]
  30. Smith S. S., Gong Q. H., Hsu F. C., Markowitz R. S., ffrench-Mullen J. M., Li X. GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid. Nature. 1998 Apr 30;392(6679):926–930. doi: 10.1038/31948. [DOI] [PubMed] [Google Scholar]
  31. Smith S. T., Brennan C., Clark A. S., Henderson L. P. GABAA receptor-mediated responses in the ventromedial nucleus of the hypothalamus of female and male neonatal rats. Neuroendocrinology. 1996 Aug;64(2):103–113. doi: 10.1159/000127105. [DOI] [PubMed] [Google Scholar]
  32. Whiting P. J., McAllister G., Vassilatis D., Bonnert T. P., Heavens R. P., Smith D. W., Hewson L., O'Donnell R., Rigby M. R., Sirinathsinghji D. J. Neuronally restricted RNA splicing regulates the expression of a novel GABAA receptor subunit conferring atypical functional properties [corrected; erratum to be published]. J Neurosci. 1997 Jul 1;17(13):5027–5037. doi: 10.1523/JNEUROSCI.17-13-05027.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Whiting P., McKernan R. M., Iversen L. L. Another mechanism for creating diversity in gamma-aminobutyrate type A receptors: RNA splicing directs expression of two forms of gamma 2 phosphorylation site. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9966–9970. doi: 10.1073/pnas.87.24.9966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wisden W., Laurie D. J., Monyer H., Seeburg P. H. The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J Neurosci. 1992 Mar;12(3):1040–1062. doi: 10.1523/JNEUROSCI.12-03-01040.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ymer S., Draguhn A., Wisden W., Werner P., Keinänen K., Schofield P. R., Sprengel R., Pritchett D. B., Seeburg P. H. Structural and functional characterization of the gamma 1 subunit of GABAA/benzodiazepine receptors. EMBO J. 1990 Oct;9(10):3261–3267. doi: 10.1002/j.1460-2075.1990.tb07525.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society

RESOURCES