Prolactin receptor in primary hyperparathyroidism--expression, functionality and clinical correlations

• Published in: PloS one Vol. 7; no. 5; p. e36448
• Main Authors: Haglund, Felix, Lu, Ming, Vukojević, Vladana, Nilsson, Inga-Lena, Andreasson, Adam, Džabić, Mensur, Bränström, Robert, Höög, Anders, Juhlin, C Christofer, Larsson, Catharina
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.05.2012; Public Library of Science (PLoS)
• Subjects: Adenoma - drug therapy; Adenoma - genetics; Adenoma - metabolism; Adult; Aged; Aged, 80 and over; Base Sequence; Biological response modifiers; Biology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breastfeeding & lactation; Calcium; Calcium (blood); Calcium Signaling - drug effects; Cohort analysis; Cytoplasm; Female; Gene expression; Gene Expression - drug effects; Genes; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Homeostasis; Hormones; Humans; Hyperparathyroidism; Hyperparathyroidism, Primary - genetics; Hyperparathyroidism, Primary - metabolism; Immunoreactivity; Interferon; Isoforms; Kinases; Lithium; Lysosomes; Male; Medical research; Medicin och hälsovetenskap; Medicine; Middle Aged; Neuroendocrine tumors; Organs; Parathyroid; Parathyroid Glands - metabolism; Parathyroid hormone; Parathyroid Hormone - secretion; Parathyroid hormones; Parathyroid Neoplasms - drug therapy; Parathyroid Neoplasms - genetics; Parathyroid Neoplasms - metabolism; Patients; Phosphorylation; Physiological aspects; Pregnancy; Prolactin; Prolactin - therapeutic use; Protein Isoforms - genetics; Protein Isoforms - metabolism; Proteins; Proteomics; Receptors; Receptors, Prolactin - genetics; Receptors, Prolactin - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Rodents; Signal transduction; Signaling; Subcellular Fractions - metabolism; Surgery; Tissues; Transcription; Transcription (Genetics); Tumors; Womens health; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0036448

Primary hyperparathyroidism (PHPT) is an endocrine disorder most commonly affecting women, suggesting a role for female hormones and/or their receptors in parathyroid adenomas. We here investigated the prolactin receptor (PRLr) which is associated with tumours of the breast and other organs. PRLr expression was investigated in a panel of 37 patients with sporadic parathyroid tumours and its functionality in cultured parathyroid tumour cells. In comparison with other tissues and breast cancer cells, high levels of prolactin receptor gene (PRLR) transcripts were demonstrated in parathyroid tissues. PRLr products of 60/70 kDa were highly expressed in all parathyroid tumours. In addition varying levels of the 80 kDa PRLr isoform, with known proliferative activity, were demonstrated. In parathyroid tumours, PRLr immunoreactivity was observed in the cytoplasm (in all cases, n = 36), cytoplasmic granulae (n = 16), the plasma membrane (n = 12) or enlarged lysosomes (n = 4). In normal parathyroid rim (n = 28), PRLr was uniformly expressed in the cytoplasm and granulae. In in vitro studies of short-term cultured human parathyroid tumour cells, prolactin stimulation was associated with significant transcriptional changes in JAK/STAT, RIG-I like receptor and type II interferon signalling pathways as documented by gene expression profiling. Moreover, PRLR gene expression in parathyroid tumours was inversely correlated with the patients' plasma calcium levels. We demonstrate that the prolactin receptor is highly abundant in human parathyroid tissues and that PRLr isoforms expression and PRLr subcellular localisation are altered in parathyroid tumours. Responsiveness of PRLr to physiological levels of prolactin was observed in the form of increased PTH secretion and altered gene transcription with significant increase of RIG-I like receptor, JAK-STAT and Type II interferon signalling pathways. These data suggest a role of the prolactin receptor in parathyroid adenomas.