T. Shimo et al., COMPARISON OF ULTRASTRUCTURAL-CHANGES IN THYROTROPHS OF THE RAT PITUITARY BETWEEN INTERMITTENT AND CONTINUOUS TREATMENTS WITH SULFADIMETHOXINE, Toxicologic pathology, 25(2), 1997, pp. 177-185
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
.