Ultrastructural Evidence of Secretion by Exocytosis and of “Synaptic Vesicle” Formation in Posterior Pituitary Glands

Abstract

EARLY electron microscopic studies of the posterior pituitary glands of rats and toads^1,2 revealed that the neurosecretory terminals contained, in addition to the electron-dense neurosecretory granules (correctly assumed to contain posterior pituitary hormones), certain structures of the same size, but electron-lucent, which were interpreted as being empty neurosecretory granules. It was concluded that on stimulation, granules release their contents in the form of a molecular dispersion which allows the hormones to traverse cytoplasm and the nerve membrane to reach the extracellular environment and, ultimately, the capillary lumen. Although various other schemes have since been proposed, they all share this concept of an essentially “intracellular” event initiating hormone release by dissociating it from sites of storage or binding (see, for example, refs. 3 and 4). And it has been emphasized repeatedly that discharge of whole granules has never been observed in electron micrographs. Nevertheless several facts are difficult to reconcile with an “intracellular” hypothesis but would favour a granule extrusion mechanism^5–7. No wholly satisfactory explanation has been offered for the presence, in the neurosecretory terminals, of a great number of synaptic vesicles—the electron-lucent structures roughly one-quarter the size of the neurosecretory granules. Because these increase in number after stimulation, and for other reasons, it has been suspected that they may serve some function in mediating release of the hormones, perhaps by releasing a substance such as acetylcholine^2,8. There is, however, very little experimental evidence for this.