Jung H, Shannon E M, Fritschy J M, Ojeda S R
Division of Neuroscience, Oregon Health Sciences University, Beaverton 97006, USA.
Brain Res. 1998 Jan 12;780(2):218-29. doi: 10.1016/s0006-8993(97)01152-9.
Gamma aminobutyric acid (GABA), the dominant inhibitory neurotransmitter in brain, is involved in the developmental regulation of LHRH secretion. Morphological studies in rodents have demonstrated that LHRH neurons are innervated by GABA-containing processes, suggesting that LHRH secretion is under direct transsynaptic GABAergic control. While GABA acts through two different receptors, GABAA and GABAB, to exert its effects, it appears that GABAA receptors are able to mediate both inhibitory and stimulatory effects of GABA on LHRH neurons. GABAA receptors are heterooligomeric ligand-gated anion channels that exhibit a diverse array of functional and pharmacological properties. This diversity is determined by the structural heterogeneity of the receptors, which are assembled from the combination of different classes of subunits with multiple isoforms. Although several studies have described the effect of GABAA receptor stimulation on LHRH and/or gonadotropin release in prepubertal animals, nothing is known about the receptor subunits that may be expressed in LHRH neurons at this phase in development. Double immunohistofluorescence followed by confocal laser microscopy revealed that subsets of prepubertal LHRH neurons are endowed with alpha 1, alpha 2, beta 2/3, and gamma 2 GABAA receptor subunits. Combined immunohistochemistry for LHRH neurons and in situ hybridization for GABAA subunit mRNAs confirmed that the genes encoding the alpha 1, alpha 2, beta 3 and gamma 2 subunits, but not the gamma 1 subunit, are expressed in LHRH neurons. Notwithstanding the relative insensitivity of these methods, both the immunohistochemical and hybridization histochemical approaches employed indicate that only a fraction of LHRH neurons are endowed with GABAA receptors. This arrangement suggests that those LHRH neurons bearing the appropriate GABAA receptors are responsible for either the entire secretory response to direct GABAergic inputs or for its initiation.
γ-氨基丁酸（GABA）是大脑中主要的抑制性神经递质，参与促性腺激素释放激素（LHRH）分泌的发育调节。对啮齿动物的形态学研究表明，LHRH神经元由含GABA的神经突起支配，这表明LHRH分泌受直接的跨突触GABA能控制。虽然GABA通过两种不同的受体GABAA和GABAB发挥作用，但似乎GABAA受体能够介导GABA对LHRH神经元的抑制和刺激作用。GABAA受体是异源寡聚体配体门控阴离子通道，具有多种功能和药理学特性。这种多样性由受体的结构异质性决定，受体由不同类别的亚基与多种亚型组合而成。尽管有几项研究描述了GABAA受体刺激对青春期前动物LHRH和/或促性腺激素释放的影响，但对于发育这个阶段LHRH神经元中可能表达的受体亚基却一无所知。双重免疫荧光结合共聚焦激光显微镜显示，青春期前LHRH神经元的亚群具有α1、α2、β2/3和γ2 GABAA受体亚基。对LHRH神经元进行免疫组织化学和对GABAA亚基mRNA进行原位杂交相结合，证实编码α1、α2、β3和γ2亚基而非γ1亚基的基因在LHRH神经元中表达。尽管这些方法相对不敏感，但所采用的免疫组织化学和杂交组织化学方法均表明，只有一部分LHRH神经元具有GABAA受体。这种排列表明，那些带有合适GABAA受体的LHRH神经元要么负责对直接GABA能输入的整个分泌反应，要么负责其启动。
