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 Ca concentration and what role their subcellular organelles played in secretion. Hyperfunctioning tissues from 1 patient with secondary parathyroid hyperplasia, 4 patients with parathyroid adenomas, and 1 patient with parathyroid carcinoma were incubated in media containing low Ca (0.75 mM), normal Ca (1.5 mM), high Ca (3.0 mM), or vinblastine (0.01 mM), a microtubular disrupter. In order to correlate ultrastructural responses with PTH secretion after incubation, tissues of 1 adenoma were objectively quantitated by stereologic techniques. Low Ca consistently stimulated mean PTH secretion from hyperplastic and adenomatous tissue, but only during the 1st h of secretion. Low Ca inconsistently stimulated carcinomatous tissue. High Ca suppressed mean PTH release from all tissues. Vinblastine did not consistently inhibit secretion from adenomatous or hyperplastic tissue. Ultrastructural analyses of adenomatous tissue showed a sparsity of granules (0.87% of cellular volume) compared to previously studied bovine tissues. Low Ca significantly increased the volume fraction of pinocytotic vesicles to 300% (P < 0.01) and reduced the surface area of straight (inactive) membrane to 60% (P < 0.01) of the normal Ca control. Secretion granules, when present, were adjacent to submembrane vesicles. The number and structure of microtubules were not changed by low or high Ca or vinblastine. Parathyroid adenomas and hyperplastic tissues can respond acutely to low Ca stimulation and high Ca suppression. The acute response to low Ca stimulation may not be sustained in some cases because of limited storage of hormone. The increase in pinocytosis in low Ca-stimulated tissue suggests a coupling of exocytosis with membrane endocytosis, possibly related to membrane recycling. The findings with vinblastine suggest that microtubular integrity is not a prerequisite for basal PTH secretion in adenomatous tissue.