Regional Specificity of Gamma-Aminobutyric Acid Receptor Regulation by Estradiol

O’Connor, Lynn H.; Nock, Bruce; McEwen, Bruce S.

doi:10.1159/000124958

Cited by 104 publications

(45 citation statements)

References 22 publications

(28 reference statements)

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“…Differences within the hypothalamus/basal forebrain as a function of sex or hormonal state in the expression of other GABA A receptor subunits (Clark et al, 1998;Nett et al, 1999;Penatti et al, 2005), in the numbers of GABA A receptors and in their binding affinities (O'Connor et al, 1988;Lasaga et al 1988;Schumacher et al, 1989;Juptner and Hiemke, 1990) have also been reported. It is likely that these differences play significant roles with respect to the expression of sexual and reproductive behaviors, but their impact on allosteric modulation of GABA A receptors in these brain regions or the potential outcome of such modulation on the expression of sexual or reproductive behaviors is currently not known.…”

Section: Steroid Modulation Of Gabaergic Transmission In Hypothalamusmentioning

confidence: 99%

Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: Effects on reproductive function

Henderson

2007

Neuropharmacology

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The hypothalamus, the seat of neuroendocrine control, is exquisitely sensitive to gonadal steroids. For decades it has been known that androgens, estrogens and progestins, acting through nuclear hormone receptors, elicit both organizational and activational effects in the hypothalamus and basal forebrain that are essential for reproductive function. While changes in gene expression mediated by these classical hormone pathways are paramount in governing both sexual differentiation and the neural control of reproduction, it is also clear that steroids impart critical control of neuroendocrine functions through nongenomic mechanisms. Specifically, endogenous neurosteroid derivatives of deoxycorticosterone, progesterone and testosterone, as well and synthetic anabolic androgenic steroids that are self-administered as drugs of abuse, elicit acute effects via allosteric modulation of γ-aminobutyric acid type A receptors. GABAergic transmission within the hypothalamus and basal forebrain is a key regulator of pubertal onset, the expression of sexual behaviors, pregnancy and parturition. Summarized here are the known actions of steroid modulators on GABAergic transmission within the hypothalamus/basal forebrain, with a focus on the medial preoptic area and the supraoptic/paraventricular nuclei that are known to be central players in the control of reproduction.

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Section: Steroid Modulation Of Gabaergic Transmission In Hypothalamusmentioning

confidence: 99%

Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: Effects on reproductive function

Henderson

2007

Neuropharmacology

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“…Steroids reduce GAD concentration in the ventral tegmentum, septum and substantia nigra (6,34,35) and daily injections of OB, that would inhibit LH release and stimulate prolactin release, induce changes in GAD activity in a number of hypothalamic regions; some reports have shown that mstrogen can increase GAD activity in the posterior hypothalamus and ME (26, 27), but it is suggested that this is an indirect effect exerted via raised prolactin levels (25,36,38). Others have shown that OB treatment reduced GAD activity in the VMN, ARC and anterior hypothalamus, but not in the POA (24), however two further papers found no change in any of the hypothalamic areas investigated (9,23). Our own results support the latter findings in that we also found no change in GAD activity in the POA, VMN, ARC/ME or ZI.…”

Section: Ospmentioning

confidence: 99%

“…GABA-containing neurons possess steroid receptors (4,5 ) and it has becn suggested that sri:roids might exert some of their CNS effects via GABAergic s! stems (6)(7)(8)(9). These effects include the control of luteinizing hormone (LH) and prolactin release and sexual behaviour.…”

mentioning

confidence: 99%

“…Since GABA is present in both neuronal and glial tissue (1, 21) changes in its concentration, and even turnover, are a less reliable index of GABAergic neuronal activity than measuring changes in glutamic acid decarboxylase (GAD), the rate-limiting synthetic enzyme for GABA, which is only present in GABA neurons (1,22). However, the reports on the effect of steroid treatment on G A D activity in hypothalamic areas are conflicting; acute or chronic oestrogen treatment having either had no effect, increasing or decreasing G A D activity (9,(23)(24)(25)(26)(27). G A D activity may reflect changes in GABA neuronal activity only after a prolonged period when any changes in G A D synthesis eventually alter levels in its stores and/or steroid may only affect certain of the multiple forms of G A D (28).…”

mentioning

confidence: 99%

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Ovarian Steroid Regulation of Glutamic Acid Decarboxylase Gene Expression in Individual Hypothalamic Nuclei

Leigh

Carter

Horton

et al. 1990

J Neuroendocrinology

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The possibility that steroids exert their effects on luteinizing hormone (LH) and prolactin release and female sexual behaviour via altering 7-arninobutyric acid (GABA) synthesis within the hypothalamus was investigated. Ovariectomized rats were treated with e$ther oil, 5 pg oestradiol benzoate (OB) or 5 pg OB plus 0.5 mg progesterone (P) 48 h later; autopsy was carried out 54 h after the OB injection. At this time, both steroid treatments stimulated prolactin release and lordotic activity. OB alone exerted a negative feedback effect on LH release while OB plus P stimulated an LH surge.The brains of the rats in these three treatment groups were microdissected and glutamic acid decarboxylase messenger ribonucleic acid (GAD mRNA) was estimated in specific hypothalamic areas obtained from individual brains; these areas included the preoptic area (POA), ventromedial nucleus (VMN), anterior medial portion of the zona incerta (ZI) and the arcuatehedian eminence area (ARC/ME). GAD mRNA concentrations were assessed by the slot-blotting technique and expressed as a ratio of GAD mRNA: b-actin mRNA.Both steroid treatments significantly reduced GAD mRNA in the ARCIME and ZI and OB plus P also reduced the concentration in the POA, while OB alone had no effect in this area. Neither treatment affected GAD mRNA in the VMN. These results indicate that when steroids stimulate LH and prolactin release and female sexual behaviour, they reduce GABA activity probably by reducing GABA synthesis in the POA, ZI and ARCIME. This suggests that GABA normally has an inhibitory influence on these parameters. G4BA synthesis does not however, appear to be involved in the negative feedback effects of steroids on LH release as measured 54 h after OB treatment.;,-,iminobutyric acid (GABA) is widely distributed in the hypothalmius with its highest concentrations in the preoptic area (POA) aiid ventromedial nucleus (VMN) (1 -3). GABA-containing neurons possess steroid receptors (4, 5 ) and it has becn suggested that sri:roids might exert some of their CNS effects via GABAergic s! stems (6-9). These effects include the control of luteinizing hormone (LH) and prolactin release and sexual behaviour. Rep x t s in the literature indicate that GABA can influence sexual bchaviour in females (10, 11) and has a dual effect on the release of I €1 and prolactin (12, 13). The results show that GABA is inhibitory to LH release in the POA and anterior medial portion o!' the zona incerta (ZI) (14-17). The site of it's stimulatory effect is not really known, although some data indicate that it may be in the medial basdl hypothalamus (12,18,19). Within the hypothalaIlIus GABA stimulates prolactin release, but it is inhibitory at the level of the pituitary (12)(13)(14)20). There are many reports investigating the inter-relationship of the gonadal steroids and GABA, in particular noting the effect of oestrogen and progesterone (P) on GABA activity in specific brain areas. Since GABA is present in both neuronal and glial tissue (1, 21) changes in its concentra...

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“…Recent reports show an effect of E, on the density of GABA receptors in the hypothalamus (40,41), therefore we theorized that oestrogenization may induce a regulation of GABA, receptors in the SCA. To study the in vivo effects of E, on GABA, and GABA, receptors we developed an in vitro quantitative autoradiographic method.…”

Section: Discussionmentioning

confidence: 91%

Analysis of the Inhibitory Effect of Oestradiol on Functional GABA/5‐HT Relationship in the Rat Suprachiasmatic Area

François‐Bellan¹,

Héry²,

Faudon³

et al. 1989

J Neuroendocrinology

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The purpose of this study was to test the capacity of oestradiol to modulate the stimulating effect of a-aminobutyric acid (GABA) on serotonin (5-HT) metabolism, previously described in the suprachiasmatic area of the male rat. After an in vivo stimulation of GABA transmission by systemic administration of a GABA-transaminase inhibitor (amino-oxyacetic acid) or a GABA, agonist (RS-baclofen), the 5-HT metabolism was studied in the suprachiasmatic area of ovariectomized, and ovariectomized oestradiol-treated rats.Amino-oxyacetic acid or RS-baclofen treatment increased the endogenous content of 5-HT in the suprachiasmatic area of males and ovariectomized rats. These two treatments were without effect in ovariectomized oestradiol-treated rats. GABA transmission stimulation induced by amino-oxyacetic acid treatment failed to affect the release and synthesis of 5-HT in ovariectomized oestradiol-treated rats while it increased these two parameters of 5-HT metabolism in the suprachiasmatic area of male and ovariectomized rats. To investigate the main target of oestradiol effect, comparative studies of the serotoninergic and GABAergic metabolism in the suprachiasmatic area were performed in the three experimental groups. Under our experimental conditions the endogenous 5-HT metabolism was similar between ovariectornized and ovariectomized oestradiol-treated rats. Nevertheless, 5-HT metabolism was higher in the two female groups than in the male group. Neither GABA metabolism nor GABAergic response to GABA-related drug treatment differed between ovariectomized, and ovariectomized oestradiol-treated rats. However, the turnover of GABA was higher when compared to the two female groups. It is concluded that the lack of 5-HT responsiveness to GABA transmission stimulation in ovariectomized oestradiol-treated rats was not related to an effect of oestradiol on 5-HT metabolism or to an effect of the steroid on GABA turnover. Furthermore, our results suggest a sex difference in the activity of serotoninergic and GABAergic systems in the suprachiasmatic area.Recently, an anatomical relationship between GABAergic and szrotoninergic terminals in the suprachiasmatic nucleus (SCN) has been reported (1). Parallel to previous reports we have shown the existence of a metabolic interaction between these two neurotransmitters. The stimulation of y-aminobutyric acid (GABA) transmission leads to an increase in serotonin (5-HT) metabolism la GABA, receptor activation in the rat's suprachiasmatic area (SCA) (2, 3). The ability of oestradiol (E,) to influence neurotransmission has long been recognized. There are numerous (4-6) examples of mechanisms by which E, may act on neurotransmitter systems. These include the modulation of neurotransmitter metabolism and effects on neurotransmitter receptor concentrations. Data concerning the effects of the steroid on 5-HT and GABA metabolism in the hypothalamus are conflicting. While some authors report that E, administration to ovariectomized animals (OVX) results in no change in 5-HT content of...

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Regional Specificity of Gamma-Aminobutyric Acid Receptor Regulation by Estradiol

Cited by 104 publications

References 22 publications

Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: Effects on reproductive function

Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: Effects on reproductive function

Ovarian Steroid Regulation of Glutamic Acid Decarboxylase Gene Expression in Individual Hypothalamic Nuclei

Analysis of the Inhibitory Effect of Oestradiol on Functional GABA/5‐HT Relationship in the Rat Suprachiasmatic Area

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