title: Secretory and ultrastructural responses of hyperfunctioning human parathyroid tissues to varying calcium concentration and vinblastine.
abstract: Parathyroid hormone (PTH) secretion from abnormal hyperfunctioning human parathyroid tissues was studied in vitro to determine whether abnormal tissues were responsive to changes in calcium concentration and what role their subcellular organelles played in secretion. Hyperfunctioning tissues from one patient with secondary parathyroid hyperplasia, four patients with parathyroid adenomas, and one patient with parathyroid carcinoma were incubated in media containing low calcium (0.75 mM), normal calcium (1.5 mM), high calcium (3.0 mM), or vinblastine (0.01 mM), a microtubular disrupter. Also, in order to correlate ultrastructural responses with PTH secretion, after incubation tissues of one adenoma were objectively quantitated by stereologic techniques. Low calcium consistently stimulated mean PTH secretion from hyperplastic and adenomatous tissue, but only during the 1st hour of secretion. Low calcium inconsistently stimulated carcinomatous tissue. High calcium suppressed mean PTH release from all tissues. Vinblastine did not consistently inhibit secretion from adenomatous or hyperplastic tissue. Ultrastructural analysis of adenomatous tissue showed a sparsity of granules (0.87 per cent of cellular volume) compared to previously studied bovine tissues. Low calcium significantly increased the volume fraction of pinocytotic vesicles to 300 per cent (p less than 0.01) and reduced the surface area of straight (inactive) membrane to 60 per cent (p less than 0.01) of the normal calcium control. Secretion granules, when present, were adjacent to submembrane vesicles. The number and structure of microtubules were not changed by low or high calcium or vinblastine. Our findings indicate that parathyroid adenomas and hyperplastic tissues can respond acutely to low calcium stimulation and high calcium suppression. However, the acute response to low calcium stimulation may not be sustained in some cases because of limited storage of hormone. The increase in pinocytosis in low calcium-stimulated tissue suggests a coupling of exocytosis with membrane endocytosis, possibly related to membrane recycling. Our findings with vinblastine suggest that microtubular integrity is not a prerequisite for basal PTH secretion in adenomatous tissue.
mesh_terms: D000236:Adenoma / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006961:Hyperparathyroidism; D008854:Microscopy, Electron; D010280:Parathyroid Glands / Q000378:metabolism* / Q000648:ultrastructure; D010281:Parathyroid Hormone / Q000378:metabolism*; D010282:Parathyroid Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D014747:Vinblastine / Q000494:pharmacology*
chemical_list: D010281:Parathyroid Hormone; D014747:Vinblastine; D002118:Calcium