Several GABA(A) receptor subunits are expressed in LHRH neurons of juvenile female rats

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, GABA(A) and GABA(B), to exert its effects, it appears that GABA(A) receptors are able to mediate both inhibitory and stimulatory effects of GABA on LHRH neurons. GABA(A) 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 GABA(A) 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 α₁, α₂, β(2/3), and γ₂ GABA(A) receptor subunits. Combined immunohistochemistry for LHRH neurons and in situ hybridization for GABA(A) subunit mRNAs confirmed that the genes encoding the α₁, α₂, β₃, and γ₂ subnnits, but not the γ₁ 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 GABA(A) receptors. This arrangement suggests that those LHRH neurons bearing the appropriate GABA(A) receptors are responsible for either the entire secretory response to direct GABAergic inputs or for its initiation.