Secretory disorders in pituitary thyrotropes of streptozocin-diabetic male rats.

Pituitary cells transport secretory products from deep cytoplasmic portions towards the subplasmalemmal region (SPL) by two mechanisms: (a) the regulated, secretagogue-dependent and (b) the secretagogue-independent constitutive pathway. Since thyrotropin (TSH) secretion is impaired in diabetes, we studied both pathways in the thyrotropes of control and streptozocin (STZ)-treated male rats. By electron microscopy, we measured the nucleus and cytoplasm area and counted the secretory granules. In 4 selected SPL (500 nm deep) areas per cell we also counted the marginated secretory granules and measured their area. Moreover, after TSH indirect immunogold labelling we counted immunogold particles on (a) the secretory granules of the SPL and (b) the intergranular SPL cytoplasm. To check the background staining we also counted immunogold particles on nonthyrotropic cells. In diabetic compared with control thyrotropes we found: (a) cytoplasmic atrophy and increased number of secretory granules per cytoplasm unit area, (b) reduced number of secretory granules in the SPL (blunted regulated secretion), (c) larger secretory granules in the SPL (abnormal secretory granule maturation), (d) decreased immunogold labelling of secretory granules in the SPL (reduced TSH transported by each secretory granule towards the cell membrane) and (e) decreased immunogold labelling of the intergranular SPL cytoplasm (blunted constitutive secretion). Our data suggest reduced regulated and constitutive TSH secretion and may thus contribute to a better understanding of the hypothyroidism in STZ-diabetic rats.

Reduced number and LH content of marginated secretory granules in pituitary gonadotropes of streptozocin-induced diabetic male rats.

The transport of secretory granules towards the subplasmalemmal (SPL) region of the luteinizing-hormone (LH) gonadotrope is controlled by the LH-releasing-hormone-dependent pathway. The SPL granules contain the most readily releasable LH. To test the effect of diabetes on both the number and LH content of marginated granules, we studied by indirect immunogold-labelling pituitaries from control and streptozocin (STZ)-treated male rats. On electron micrographs we measured the areas of the gonadotrope nucleus and cytoplasm, counted all secretory granules, and counted and measured secretory granules in selected SPL regions. Furthermore, we counted gold particles (IG) on (a) the secretory granules of the SPL regions, (b) the intergranular SPL cytoplasm and (c) the region outside the cell. Finally, in order to evaluate possible diabetes-related changes of the pituicyte cytoskeleton, we measured by densitometry actin, tubulin, vimentin, and desmin in immunocytochemically stained pituitary sections. In diabetic compared with control cells of the studied pituitary region, we observed: (a) cytoplasmic atrophy; (b) the number of secretory granules per unit area increased in the total cytoplasm, and decreased in the SPL cytoplasm (lowered regulated secretion); (c) decreased IG labelling in the SPL granules (reduced amount of hormone transported by each granule towards the cell membrane); (d) decreased IG labelling in the integranular SPL cytoplasm (reduced constitutive secretion), and (e) strongly increased actin and desmin, yet unchanged tubulin and vimentin immunoreactivity. Our data indicate that both regulated and constitutive secretion are possibly reduced in gonadotropes of diabetic male rats. The cytoskeletal alterations may also contribute to the reduced regulated secretion.