An autocrine role for pituitary GABA: Activation of GABA-B receptors and regulation of growth hormone levels

There is increasing evidence suggesting that the neurotransmitter
gamma-aminobutyric acid (GABA) is a local factor involved in the
regulation of endocrine organs. Examples of such functions are
documented in the pancreas, but recent results suggest that GABA
may act in a similar way in the pituitary, in which GABA receptors
are expressed and pituitary growth hormone (GH) cells provide a
source of GABA. We hypothesised that GABA secreted in somatotropes
may act as an autoregulatory signaling molecule. To test this
hypothesis we first examined the nature of GABA receptors expressed
by GH cells. RT-PCR analysis demonstrated that GABA-B receptor
subunits R1 and R2 are present in the whole rat pituitary. Laser
microdissection of immunostained GH cells, followed by RT-PCR as
well as immunoelectron microscopy, showed that GABA-B receptors are
expressed on somatotropes. To investigate GABA-B receptor function
in somatotropes, we used rat GH3 adenoma cells, which, like
pituitary GH cells, express GABA-B R1 and R2 (as assessed by RT-PCR
and immunoelectron microscopy) and produce GABA (checked by high
performance liquid chromatography). After inhibition of endogenous
GABA synthesis, GH production was stimulated by baclofen, a
chromatography). After inhibition of endogenous GABA synthesis, GH
production was stimulated by bactofen, a GABA-B receptor agonist.
By contrast, blocking GABA-B receptors by an antagonist, phaclofen,
decreased GH levels. We conclude that in GH-producing cells, GABA
acts as an autocrine factor via GABA-B receptors to control GH
levels. Copyright (C) 2002 S. KargerAG, Basel.