Evidence for a GABAergic system in rodent and human testis: Local GABA production and GABA receptors

The major neurotransmitter of the central nervous system,
gamma-aminobutyric acid (GABA), exerts its actions through GABA(A),
GABA(B) and GABA(C) receptors. GABA and GABA receptors are,
however, also present in several non-neural tissues, including the
endocrine organs pituitary, pancreas and testis. In the case of the
rat testis, GABA appears to be linked to the regulation of steroid
synthesis by Leydig cells via GABA(A) receptors, but neither
testicular sources of GABA, nor the precise nature of testicular
GABA receptors are fully known. We examined these points in rat,
mouse, hamster and human testicular samples. RT-PCR followed by
sequencing showed that the GABA-synthesizing enzymes glutamate
decarboxylase (GAD) 65 and/or GAD67, as well as the vesicular GABA
transporter vesicular inhibitory amino acid transporter
(VIAAT/VGAT) are expressed. Testicular GAD in the rat was shown to
be functionally active by using a GAD assay, and Western blot
analysis confirmed the presence of GAD65 and GAD67. Interstitial
cells, most of which are Leydig cells according to their location
and morphological characteristics, showed positive immunoreaction
for GAD and VIAAT/VGAT proteins. In addition, several GABA(A)
receptor subunits (alpha1-3, beta1-3, gamma1-3), as well as GABAB
receptor subunits R1 and R2, were detected by RT-PCR. Western blot
analysis confirmed the results for GABA(A) receptor subunits
beta2/3 in the rat, and immunohistochemistry identified
interstitial Leydig cells to possess immunoreactive GABA(A)
receptor subunits beta2/3 and alpha1. The presence of GABA(A)
receptor subunit alpha1 mRNA in interstitial cells of the rat
testis was further shown after laser microdissection followed by
RT-PCR analysis. In summary, these results describe molecular
details of the components of an intratesticular GABAergic system
expressed in the endocrine compartment of rodent and human testes.
While the physiological significance of this peripheral
neuroendocrine system conserved throughout species remains to be
elucidated, its mere presence in humans suggests the possibility
that clinically used drugs might be able to interfere with
testicular function. Copyright (C) 2003 S. Karger AG, Basel.