Leptin and leptin receptor expression in normal and neoplastic human pituitary: Evidence of a regulatory role for leptin on pituitary cell proliferation

Leptin is a circulating hormone secreted by adipose and a few other tissues . The leptin receptor consists of a single transmembrane-spanning polypepti de that is present as a long physiologically important form as well as in s everal short isoforms. Recent studies have suggested that the anterior pitu itary may have a role in the regulatory effects of leptin in animal models. To test this possibility in human pituitaries, we examined the expression of leptin and OB-R in normal and neoplastic pituitaries, and the possible f unctions of leptin in the pituitary were also analyzed. Leptin was present in 20-25% of anterior pituitary cells and was expressed in most normal ante rior pituitary cells, including ACTH (70% of ACTH cells), GH (21%), FSH (33 %), LH (29%), TSH (32%), and folliculo-stellate cells (64%), but was coloca lized with very few PRL cells (3%), as detected by double labeling immunohi stochemistry with two different antileptin antibodies. In addition, leptin expression was detected by RT-PCR in some pituitary tumors, including ACTH (three of four), GH (one of four), null cells (two of four), and gonadotrop h (one of four) tumors as well as in normal pituitary. Immunohistochemical staining showed greater immunoreactivity for leptin in normal pituitaries c ompared to adenomas. Treatment of an immortalized cultured anterior pituita ry cell line, HP75, with leptin stimulated pancreastatin secretion in vitro . Leptin also inhibited cell growth in the human HP75 and in the rat pituit ary GH(3) cell lines. Both long (OB-Rb) and common (OB-Ra) forms of the lep tin receptor messenger ribonucleic acid and leptin receptor protein were ex pressed in normal and neoplastic anterior pituitary cells. These findings s how for the first time that leptin is expressed by most human anterior pitu itary cell types and that there is decreased leptin protein immunoreactivit y in pituitary adenomas compared to that in normal pituitary tissues. We al so show that OB-Rb is widely expressed by normal and neoplastic anterior pi tuitary cells, implicating an autocrine/paracrine loop in the production an d regulation of leptin in the pituitary.