Propylthiouracyl-induced hypothyroidism results in reversible transdifferentiation of somatotrophs into thyroidectomy cells. A morphologic study of the rat pituitary including immunoelectron microscopy

Abstract

Two-month-old female Fischer-344 rats were rendered hypothyroid by ingestion of propyl-thiouracyl (PTU) (0.1% in drinking water) and sacrificed 3, 7, 14, and 28 days after the start of PTU administration as well as 3, 7 and 14 days after interruption of a 14-day PTU treatment. Controls received no PTU. The pituitaries were studied by histology, immunohistochemistry, electron microscopy, and immunoelectron microscopy, using the immunogold double-labeling technique. In the course of hypothyroidism, pituitary thyrotrophs had undergone the well-known thyroidectomy change. In addition, a contingent of growth hormone (GH) cells lost their large secretory granules, enlarged, displayed progressive dilation of rough endoplasmic reticulum, thereby transforming into thyroidectomy cells. These bihormonal thyrosomatotrophs contained gH in their secretory granules and thyrotropin in the dilated rough endoplasmic reticulum as documented by the immunogold double-labeling method for GH and thyrotropin. After discontinuation of PTU treatment, a rapid increase in size, number and GH labeling of secretory granules and simultaneous involution of distended rough endoplasmic reticulum with reduction of thyrotropin labeling took place in thyrosomatotrophs. A practically complete restitution of normal pituitary structure was seen in 2 weeks. Results implicate that, contrary to previously accepted concepts, adenohypophysial cells may not be irreversibly committed to one morphologically recognizable cell line.