Leptin is a circulating hormone secreted by adipose and a few other tissues. The 
leptin receptor consists of a single transmembrane-spanning polypeptide that is 
present as a long physiologically important form as well as in several short 
isoforms. Recent studies have suggested that the anterior pituitary 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 functions of leptin in 
the pituitary were also analyzed. Leptin was present in 20-25% of anterior 
pituitary cells and was expressed in most normal anterior pituitary cells, 
including ACTH (70% of ACTH cells), GH (21%), FSH (33%), LH (29%), TSH (32%), 
and folliculo-stellate cells (64%), but was colocalized with very few PRL cells 
(3%), as detected by double labeling immunohistochemistry 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 gonadotroph (one of four) tumors as well as in normal 
pituitary. Immunohistochemical staining showed greater immunoreactivity for 
leptin in normal pituitaries compared to adenomas. Treatment of an immortalized 
cultured anterior pituitary cell line, HP75, with leptin stimulated 
pancreastatin secretion in vitro. Leptin also inhibited cell growth in the human 
HP75 and in the rat pituitary GH3 cell lines. Both long (OB-Rb) and common 
(OB-Ra) forms of the leptin receptor messenger ribonucleic acid and leptin 
receptor protein were expressed in normal and neoplastic anterior pituitary 
cells. These findings show for the first time that leptin is expressed by most 
human anterior pituitary cell types and that there is decreased leptin protein 
immunoreactivity in pituitary adenomas compared to that in normal pituitary 
tissues. We also show that OB-Rb is widely expressed by normal and neoplastic 
anterior pituitary cells, implicating an autocrine/paracrine loop in the 
production and regulation of leptin in the pituitary.