Neurohormonal Modulators in the Parathyroid Gland. Localization and regulation

Abstract: The occurrence and distribution of neurohormonal peptides, neuroendocrine markers and receptors in parathyroid nerve fibers and endocrine cells are described, using immunocytochemistry, in situ hybridization, image analysis and reverse transcriptase polymerase chain reaction. Immunocytochemical studies revealed that parathyroid glands of chicken, rat, guinea-pig, cat, dog and sheep contained adrenergic-, cholinergic-, and peptide-containing nerve fibers. The peptides contained in nerve fibers comprised calcitonin gene-related peptide (CGRP), galanin, neuropeptide Y (NPY), pituitary adenylate cyclase activating peptide (PACAP), substance P (SP) and vasoactive intestinal polypepetide (VIP). Many nerve fibers contained protein gene product 9.5 (PGP 9.5). In human parathyroid glands and adenomas there were a rich supply of NPY-containing nerve fibers. In addition, PGP 9.5, synaptophysin, tyrosine hydroxylase (TH), CGRP, PACAP, SP and VIP were detected. These nerve fibers were located preferentially around blood vessels but they also occurred scattered in the parenchyma or within the capsule. In rat, during development, PGP 9.5- and synaptophysin-containing nerve fibers appeared already before birth. Such fibers and peptide-containing ones gradually increased postnatally. In rat, after parathyroid autotransplantation, nerve fibers containing PGP 9.5 and NPY appeared along blood vessels 1 week after transplantation, whereas CGRP- and VIP-containing nerve fibers could not be detected until 20 weeks after transplantation. In endocrine cells of the rat parathyroid glands, parathyroid hormone (PTH)-, chromogranin A (Cg A)-, pancreastatin- and endothelin-immunoreactivity was detected during ontogeny and after parathyroid autotransplantation. The cells contained PTH, Cg A, pancreastatin and endothelin already before birth. PTH and Cg A mRNA increased stepwise, first at birth and then at the time of weaning. Endothelin mRNA levels were higher during development than in adult rats. After parathyroid transplantation, PTH-, Cg A-, pancreastatin- and endothelin- immunoreactivity was weak. PTH mRNA levels were low during the 20 weeks studied. Cg A mRNA levels were not decreased until 5-10 weeks after grafting. Endothelin mRNA expression was generally lower after transplantation. In human parathyroid glands and adenomas PTH, Cg A, pancreastatin and nitric oxide synthase (NOS) were demonstrated in endocrine cells. PTH and Cg A mRNA levels correlated positively in parathyroid adenomas. NOS was demonstrated in oxyphilic cells, in endothelial and smooth muscle cells and in a subpopulation of chief cells. In addition, expression of endothelin (ETA, ETB) and NPY (Y1) receptor mRNA was demonstrated in normal human parathyroid glands, adenomas and hyperplasias. The findings of several neurohormonal messengers, in addition to PTH, may indicate a potential role as modulators of parathyroid function.