COMPARISON OF ULTRASTRUCTURAL-CHANGES IN THYROTROPHS OF THE RAT PITUITARY BETWEEN INTERMITTENT AND CONTINUOUS TREATMENTS WITH SULFADIMETHOXINE

To clarify relationships between serum thyroid-stimulating hormone (TS H) levels and ultrastructural changes in thyrotrophs caused by intermi ttent or continuous treatments with antithyroid compound, male Fischer -344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN) were given water containing 0.1% sulfadimethoxine (SM) for 8 wk and then s acrificed (Group 1). Additional groups were examined 2 wk after withdr awal (Group 2), after 4 wk retreatment following a 2-wk withdrawal per iod (Group 3), and after 14 wk continuous exposure (Group 4). Control rats (Group 5) remained untreated for 8 wk after the DHPN initiation. Microscopic examination revealed hypertrophy of thyrotrophs and deplet ion of TSH-positive material in Groups 1, 3, and 4 but a return to nor mal in Group 2. Electron microscopic examination of thyrotrophs in the anterior pituitary in Groups 1, 3, and 4 revealed dilated rough endop lasmic reticulum (ER) cisternae with intracisternal dense granules as well as diminished numbers of intracytoplasmic secretory granules, the se changes being most marked in Group 1 and least pronounced in Group 3. The number of intracytoplasmic secretory granules in Group 3 was mu ch lower than in Group 4, as demonstrated by morphometric analysis. In Group 2, thyrotrophs showed dilated rough ER cisternae without intrac isternal dense granules and essentially the same component of intracyt oplasmic secretory granules as Group 5. The present study suggests tha t while prolonged continuous treatment with SM results in gradual accl imation to an increased demand for TSH, intermittent treatment elicits a persistent state of reduced TSH storage in thyrotrophs due to a con tinued strong feedback through the hypothalamus-pituitary-thyroid axis .