Receptors and Sites of Synthesis and Storage of γ-Aminobutyric Acid in Human Pituitary Glands and in Growth Hormone Adenomas

Abstract

gamma-Aminobutyric acid (GABA) is an important regulatory factor of pituitary gland function, which in addition to hypothalamic neurons, can be derived from intrapituitary sources, ie, growth hormone (GH) cells of rat and monkey. We report that human pituitary glands also express 2 isoforms of the GABA-synthesizing enzyme glutamate decarboxylase (GAD 65; GAD 67), the vesicular GABA transporter (VGAT), and multiple subunits of GABA (A, B, and C) receptors. GABA production and storage occurs in GH cells, as demonstrated by cellular colocalization of immunoreactive GAD and VGAT in GH cells and by reverse transcription-polymerase chain reaction analysis of laser capture-microdissected immunostained GH cells. It is interesting that human pituitary GH adenomas share expression of VGAT and GABA receptors with normal pituitary glands but lack GAD 65. We propose that GABA, synthesized by GH cells, might act as a paracrine or autocrine regulating factor in the human pituitary gland and in human GH adenoma. Because many drugs interfere with GABA function, the identification of GABA system components might have clinical implications.