In vitro effect of human recombinant leptin and expression of leptin receptors on growth hormone-secreting human pituitary adenomas.
OBJECTIVE
Leptin is a circulating hormone secreted by adipose tissue and a few other tissues. It has recently been demonstrated that leptin and leptin receptors are expressed in normal and adenomatous pituitary cells. The aim of this study was to investigate the effect of recombinant human leptin on GH release from adenomatous GH-secreting cells in culture. Specimens were obtained from 10 patients with acromegaly who had undergone selective transsphenoidal adenomectomy. Cells (2 x 10(5)/well) preincubated for 24 h with leptin (10(-10)-10(-8) m) or control medium were exposed to GHRH for 2 h. The GH released into the medium was measured before and after GHRH incubation. The expression of leptin receptor isoforms was evaluated by reverse-transcriptase polymerase chain reaction (RT-PCR) in cells obtained from five adenomas.


RESULTS
After the first incubation, there was a slight dose-dependent leptin-induced decrease in GH released into the medium. A significant increase in GH release after GHRH was noted from cells previously exposed to leptin in comparison with cells incubated with medium alone. Expression of leptin receptors was found in two out of five GH-secreting adenomas evaluated.


CONCLUSIONS
Our data confirm that some, but not all, GH-secreting adenomas express leptin receptors. Leptin seems to exert both a slight inhibitory effect on spontaneous GH secretion and a stimulatory effect on GHRH-stimulated GH secretion from GH-secreting adenomatous tissue.
D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D015870:Gene Expression; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C515448:LEPR protein, human; D020738:Leptin; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone