Rab
proteins are low molecular weight
GTP-binding proteins. Among these
proteins, the Rab3
isoforms are considered to be involved in the exocytosis of synaptic vesicles and secretory granules in the central nervous system and anterior pituitary gland. In recent reports, the expression of Rab3
isoforms in anterior pituitary glands of mammalian species was extensively investigated. In the present study, we investigated the localization of
Rab3 protein in 5 human nontumorous pituitaries and 114 human
pituitary adenomas using immunohistochemical methods. In five human nontumorous pituitaries,
Rab3 protein was expressed in the cytoplasm of anterior pituitary cells. Double staining for
anterior pituitary hormones revealed the expression of Rab3 in
growth hormone-secreting cells, but rare expression was observed in the other anterior pituitary
hormone-secreting cells. Among the
pituitary adenomas, 71 (62.3%) of 114
pituitary adenomas were positive for Rab3. Among the different
pituitary adenoma types, the incidence of Rab3 immunopositivity was highest in
growth hormone-secreting
adenomas (100%), followed by
adrenocorticotropic hormone-secreting
adenomas (71.4%),
thyroid-stimulating hormone-secreting
adenomas (57.1%), nonfunctioning
adenomas (56.0%), and
prolactin-secreting
adenomas (33.3%). After an embedding immunoelectron microscopic study, Rab3 was localized along the limiting membrane of secretory granules in the Rab3-positive
pituitary adenomas. Western blotting showed the molecular weight of Rab3 to be 25 kDa in the
pituitary adenomas, which were immunohistochemically positive for
Rab3 protein. These results suggested that Rab3 might be involved in regulating the exocytosis of secretory granules of the anterior pituitary cells, especially
growth hormone-secreting ones, which are particularly characterized by densely granulated cytologic features.