Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion.
We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid hormone (PTH) secretion in parathyroid neoplasms.



The parathyroid glands acting through PTH play a critical role in the regulation of serum calcium. Based on leptin's recently discovered role in bone metabolism, we hypothesized these glands were the sites of a functional interaction between these 2 hormones.



From July 2010 to July 2011, 96 patients were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for surgical intervention provided informed consent. Immediately after parathyroidectomy, 100 to 300 mg of adenomatous or hyperplastic diseased parathyroid tissue was prepared and processed according to requirements of the following: in situ hybridization, immunohistochemistry, immunofluorescence by conventional and spinning disc confocal microscopy, electron microscopy, parathyroid culture, whole organ explant, and animal model assays.



Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were detected in an overlapping fashion in parathyroid chief cells in adenoma and hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT-PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells. PTH secretion in explants increased in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline.



Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release.
*Section of Plastic and Reconstructive Surgery, Yale University School of Medicine, New Haven, CT †Section of Endocrine Surgery, Endocrinology, Surgical Oncology, Yale University School of Medicine, New Haven, CT ‡Yale Center of Analytical Science, Yale University School of Public Health, New Haven, CT §Department of Cell Biology, Yale University School of Medicine, New Haven, CT.
Don
D
Hoang
Niclas
N
Broer
Julie A
JA
Sosa
Nathalie
N
Abitbol
Xiaopan
X
Yao
Fangyong
F
Li
Felix
F
Rivera-Molina
Derek K
DK
Toomre
Sanziana A
SA
Roman
Gloria
G
Sue
Samuel
S
Kim
Alexander Y
AY
Li
Glenda G
GG
Callender
Christine
C
Simpson
Deepak
D
Narayan
D000236:Adenoma / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D006961:Hyperparathyroidism / Q000378:metabolism; D006965:Hyperplasia / Q000378:metabolism; D007150:Immunohistochemistry; D020738:Leptin / Q000378:metabolism*; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D010280:Parathyroid Glands / Q000378:metabolism* / Q000473:pathology; D010281:Parathyroid Hormone / Q000378:metabolism*; D010282:Parathyroid Neoplasms / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D054411:Receptors, Leptin / Q000037:antagonists & inhibitors / Q000378:metabolism
D020738:Leptin; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D054411:Receptors, Leptin