Immunocytochemical studies of the rat adenohypophysis identified a cell population that exhibits immunoreactivity for type-2 vesicular glutamate transporter (VGLUT2), a marker for glutamatergic neuronal phenotype. The in situ hybridization detection of VGLUT2 mRNA expression in adenohypophysial cells verified that VGLUT2 immunoreactivity is due to local synthesis of authentic VGLUT2. Dual-immunofluorescent studies of the hypophyses from male rats showed the presence of VGLUT2 in high percentages of LH- (93.3 ± 1.3%), follicle stimulating hormone- (44.7 ± 3.9%), and TSH- (70.0 ± 5.6%) immunoreactive cells and its much lower incidence in cells of the prolactin, growth hormone and ACTH phenotypes. Quantitative in situ hybridization studies have established that the administration of a single dose of 17--Estradiol (20 µg/kg; sc.) to ovariectomized rats significantly elevated VGLUT2 mRNA in the adenohypophysis 16 h post-injection. Thyroid hormone dependence of VGLUT2 expression was addressed by the comparison of hybridization signals in animal models of hypo and hyperthyroidism to those in euthyroid controls. While hyperthyroidism had no effect on VGLUT2 mRNA, hypothyroidism increased adenohypophysial VGLUT2 mRNA levels. This coincided with a decreased ratio of VGLUT2-immunoreactive TSH cells, regarded as a sign of enhanced secretion.

The presence of the glutamate marker VGLUT2 in gonadotrope and thyrotrope cells, and its up-regulation by estrogen or hypothyroidism, address the possibility that endocrine cells of the adenohypophysis may co-secrete glutamate with peptide hormones in an estrogen- and thyroid status-regulated manner. The exact roles of endogenous glutamate observed primarily in gonadotropes and thyrotropes, including its putative involvement in autocrine/paracrine regulatory mechanisms, will require clarification.