Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion
Autor: | Samuel Kim, Glenda G. Callender, Derek Toomre, Nathalie Abitbol, Julie Ann Sosa, Xiaopan Yao, Felix Rivera-Molina, Alexander Y. Li, Fangyong Li, Niclas Broer, Sanziana A. Roman, Deepak Narayan, Christine A. Simpson, Gloria R. Sue, Don Hoang |
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Rok vydání: | 2017 |
Předmět: |
Adenoma
Leptin 0301 basic medicine Parathyroidectomy medicine.medical_specialty medicine.medical_treatment Parathyroid hormone 030209 endocrinology & metabolism Parathyroid Glands 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Humans Prospective Studies RNA Messenger Microscopy Immunoelectron Cells Cultured Mice Knockout Calcium metabolism Hyperparathyroidism Hyperplasia Microscopy Confocal Leptin receptor Parathyroid neoplasm business.industry Parathyroid chief cell medicine.disease Immunohistochemistry Parathyroid Neoplasms 030104 developmental biology Endocrinology Microscopy Fluorescence Parathyroid Hormone Receptors Leptin Parathyroid hormone secretion Surgery business hormones hormone substitutes and hormone antagonists |
Zdroj: | Annals of Surgery. 266:1075-1083 |
ISSN: | 0003-4932 |
DOI: | 10.1097/sla.0000000000002004 |
Popis: | Objective 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. Background 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. Methods 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. Results 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. Conclusions Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release. |
Databáze: | OpenAIRE |
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