The release of leptin and its effect on hormone release from human pituitary adenomas.
BACKGROUND
Leptin is the protein product of the obese gene, known to play an important role in body energy balance. The leptin receptor exists in numerous isoforms, the long isoform being the major form involved in signal transduction. Leptin expression has recently been demonstrated in the human pituitary, both in normal tissue and in pituitary adenomas. The long isoform of the leptin receptor has also been shown to be present in pituitary adenomas; however, contrasting results have been obtained regarding its expression in the normal human pituitary.


OBJECTIVE
The aim of this study was (i) to investigate the presence and pattern of distribution of leptin mRNA and the long isoform of its receptor mRNA in the normal pituitary and in different types of pituitary adenomas with RT-PCR; (ii) to study leptin secretion from human pituitary tumours in culture and (iii) to assess in vitro pituitary hormone release following stimulation with human leptin.


RESULTS
Leptin receptor long isoform expression was detected in 2/4 GH-secreting adenomas, 12/17 non-functioning adenomas, 5/9 ACTH-secreting adenomas, 1/2 prolactinomas, 2/2 FSH-secreting adenomas and 5/5 normal pituitaries. The receptor long isoform did not segregate with any particular tumour type, and varying levels of expression were detected between the tissues studied. Leptin mRNA was detected at a low level of expression in 2/7 GH-secreting adenomas, 9/14 non-functioning adenomas, 2/3 ACTH-secreting adenomas, 1/3 prolactinomas and 1/3 FSH-secreting adenomas. We were unable to detect leptin mRNA in any of the five normal pituitaries removed at autopsy; however, immunostaining of a non-tumorous pituitary adjacent to an adenoma removed at transsphenoidal surgery showed scattered leptin positive cells. Culture of pituitary adenomas showed that 16/47 released leptin into the incubation media. Leptin release did not correlate with tumour type or with any of the other pituitary hormones released. In vitro leptin stimulation of pituitary tumours caused stimulation of FSH and alpha-subunit secretion from a non-functioning adenoma and TSH secretion from a somatotroph adenoma.


CONCLUSIONS
We conclude that not only is leptin stored within the pituitary, but it may also be released from pituitary cells and modulate other pituitary hormone secretion. Pituitary leptin may therefore be a novel paracrine regulator of pituitary function.
Korbonits
M
M
Department of Endocrinology, St Bartholomew's Hospital, London EC1A 7BE, UK.
Chitnis
M M
MM
Gueorguiev
M
M
Norman
D
D
Rosenfelder
N
N
Suliman
M
M
Jones
T H
TH
Noonan
K
K
Fabbri
A
A
Besser
G M
GM
Burrin
J M
JM
Grossman
A B
AB
D000236:Adenoma / Q000737:chemistry / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000032:analysis / Q000378:metabolism; D000704:Analysis of Variance; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics; D013006:Growth Hormone / Q000032:analysis / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019899:Paracrine Communication; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000737:chemistry / Q000378:metabolism*; D015175:Prolactinoma / Q000737:chemistry / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; C515448:LEPR protein, human; D020738:Leptin; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone