Cytochemical aspects on the secretion mechanism of the thyroid gland.

Abstract

OrientationIn the thyroid hormones, triiodothyronine (T3) and thyroxine (T4) are not peptides but characteristic amino acid derivatives, derived from only two molecules of iodotyrosine linked by ether bond (-o-). In all the peptide-secreting cells, the secretory granule, which originates from the rough endoplasmic reticulum and Golgi apparatus system, is released into the connective tissue space. However, formation of T3 and T4 in the thyroid requires more complicated steps. The hormones are not synthesized directly from their constituents, tyrosine and iodine in the cell, but a part of their synthetic process takes place in the extracellular lumen, called the follicle lumen. The secretory process of T3 and T4 is as follows: (i) synthesis of a large molecular glycoprotein (MW 660,000), called thyroglobulin in the follicle epithelial cell, (ii) release of thyroglobulin into the follicle lumen, (iii) iodination of the tyrosyl residues of thyroglobulin, and coupling of iodotyrosine residues to make T3 or T4 in thyroglobulin, (iv) reabsorption of thyroglobulin from the follicle lumen into the follicle epithelial cell, (v) hydrolysis of thyroglobulin for the liberation of T3 and T4, and (vi) release of T3 and T4 from the follicle epithelial cell into the connective tissue space. The present paper deals with the outline of cytochemical aspects on the secretion mechanism of the thyroid gland, except for the parafollicular cell, which secretes a peptide hormone called thyrocalcitonin. Autoradiography of 3H-amino acidThe follicle epithelial cell has to synthesize a high-molecular-weight glycoprotein, called thyroglobulin. As in other protein secretory cells, the proteinous part of thyroglobulin is synthesized at the attached ribosomes of the well developed rough endoplasmic reticulum and is stored in the cisternae of this organelle. Then the synthesized protein is transported to the Golgi apparatus, where the secretory granules, about 200 nm in diameter, arise. By the electron microscopic autoradiography of 3H-amino acid, the intracellular route for the synthesis and release of thyroglobulin has been clarified (3,6,18). In our data, the labeled amino acid first appears in the cisternae of rough endoplasmic reticulum within 15 min after the intraperitoneal injection of 3H-leucine. Then the silver grains begin to appear in the Golgi apparatus and subapical vesicles (secretary granules) after 30-45 min and in the follicle lumen after 45 min (3, 6).The proteinous part of thyroglobulin has to be bound to carbohydrate elements to become a glycorpotein. Using electron microscopic autoradiography of 3H-mannose, 3H-galactose, and 3H-fucose, the problem concerning the site of incorpo-391