Morphological and functional changes during thyroid hyperplasia and involution in C3H Mice: evidence for folliculoneogenesis during involution.

Involution of thyroid hyperplasia was induced in C3H mice by discontinuing a goitrogenic treatment (low iodine diet supplemented with 0.25% propylthiouracil) and refeeding a normal iodine diet. Thyroid involution was studied by morphological, histochemical, autoradiographic, and stereological methods. The onset of the involution was characterized by an early accumulation of colloid, the presence of necrotic cells in the follicular lumina, and the appearance of homogeneous microcavities in the epithelial layers. The intraepithelial microcavities had the same morphological and functional properties as the follicular lumina. They were limited by a membrane covered with microvilli; polysaccharides and peroxidase activity were detected on their membranes, and 125I-labeling was marked in their lumina. Thin serial sections demonstrated that the microlumens originated from the intercellular space; plasma membranes differentiated into junctional complexes, and a narrow lumen limited by a membrane covered with short microvilli was formed in the intercellular space between the junctions. Later on, the newly formed microlumens fused to form new follicles with a cloverleaf pattern. As a consequence of the folliculogenesis, the total number of follicles doubled after 8 days of involution. This increase in number was mainly due to the presence of a population of small follicles. The folliculogenesis was associated in the first 4 days of involution with an active cellular multiplication which compensated for the early cell necrosis and led to a doubled number of epithelial cells. The increase in the total number of follicles and cells could partially explain the persistence of a relatively high thyroid weight after involution of hyperplasia.