Subcellular mechanisms of parathyroid hormone secretion: ultrastructural changes in response to calcium, vitamin A, vinblastine, and cytochalasin B.

The effects of various agents on the in vitro secretion of parathyroid hormone (PTH) were studied previously, using bovine glands. Low calcium, (0.75 mM), vitamin A (vit A), and cytochalasin B stimulated secretion, and high calcium (3.0 mM) and vinblastine (VB) inhibited secretion, whereas hydrocortisone and VB inhibited the vit A-induced PTH secretion. In order to define subcellular mechanisms of PTH release at the morphologic level, a semiquantitative analysis of ultrastructural characteristics has been made on the same tissue with the same agents. Low calcium increased convolutions of the intercellular membrane, the number of large type I secretory granules, phagolysosomes, lipoid vacuoles, and lamellae of endoplasmic reticulum. Vit A and cytochalasin B widened intercellular spaces and increased intercellular membranous interdigitations, the number of type I secretory granules, and phagolysosomes. Vit A also dilated Golgi membranes, and cytochalasin B also increased the number of small type II secretory granules and the margination of granules along the cell membrane. High calcium increased the number of phagolysosomes and crinophagic and lipoid vacuoles. VB decreased the number of microtubules and caused stacking of endoplasmic reticulum lamellae. VB or hydrocortisone diminished some of the ultrastructural effects of vit A. The common ultrastructural findings in response to stimulation of PTH secretion by low calcium, vit A, and cytochalasin B raise the possibility that these agents may facilitate PTH secretion through a common messenger or may directly interact with the cell membrane or with the secretion granule for phagolysosome (or both). Our findings are consistent with the role of VB as a microtubule disrupter, but also suggest that VB inhibits PTH secretion through other mechanisms involving the cell membrane and endoplasmic reticulum. Microtubules may facilitate basal PTH secretion and vit A-induced secretion; however, since VB does not inhibit low calcium-stimulated PTH secretion and, ultrastructurally, microtubules were not increased in the presence of low calcium, low calcium-stimulated secretion is not dependent upon microtubular function.