Hormonal effects on development of the secretory apparatus of chief cells.

We used light microscopy, transmission electron microscopy, and stereological point-counting methods to investigate the response of rat gastric chief cells to corticosterone and thyroxine during postnatal development. Administration of corticosterone or thyroxine to normal animals in the first two postnatal weeks increased relative numbers of chief cells in the fundic mucosa but did not change the absolute number of total cells in each gland. The chief cells displayed more rough endoplasmic reticulum, zymogen granules, and Golgi saccules in corticosterone- or thyroxine-injected rats than in normal control rats. When rats were either adrenalectomized or made hypothyroid using propylthiouracil, the number of chief cells dramatically decreased. Ultrastructural studies of chief cells from adrenalectomized or hypothyroid rats showed retarded differentiation as indicated by increased free ribosomes, less rough endoplasmic reticulum, fewer zymogen granules, and poorly developed Golgi apparatuses. In adrenalectomized animals, thyroxine replacement alone failed to induce the histological maturation of chief cells, but addition of corticosterone stimulated chief cell differentiation. In hypothyroid animals, either thyroxine or corticosterone replacement restored the differentiation of chief cells to normal levels. Our data indicate that 1) corticosterone is necessary for gastric chief cell maturation during postnatal development, 2) a decrease or loss in either corticosterone and/or thyroxine results in retarded chief cell differentiation and functional activity, and 3) the effect of thyroxine on chief cell development is secondary to an accompanying increase in serum corticosterone.