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The question of whether thyroxine (T₄) and TRH have a mitogenic effect on pituitary thyrotrophs and somatotrophs in thyroidectomized rats was investigated. Mitoses were counted in hematoxylin–eosin-stained or periodic acid–Schiff–hematoxylin-stained pituitary slides or immunostained for TSH or GH using male rats thyroidectomized for 5 months. Ten days before they were killed groups of rats were injected with different doses of T₄ (0·5, 3 or 10 µg i.m. every second day for 10 days), TRH alone (100 ng s.c. three times a day for 10 days), or T₄ plus TRH (same doses as above). Mitoses (stopped with colchicine) were counted in 1 mm² areas at a magnification of x 1000. In thyroidectomized rats, mitoses were not significantly increased and treatment with TRH or 0·5 µg T₄ alone in thyroidectomized rats did not affect mitotic counts. In thyroidectomized rats treated with higher doses of T₄, mitoses were increased in a dose-dependent fashion. Simultaneous administration of TRH and T₄ had a significant synergistic effect on pituitary mitoses in a T₄ dose-dependent manner. The treatments also had differential effects on the relative percentages of cellular types in mitosis. Thus, 60% somatotrophs and 12·5% thyrotrophs were found in the euthyroid group. In thyroidectomized and thyroidectomized plus TRH groups, no somatotrophs in mitosis were seen, while thyrotrophs were 28·5% and 33·3% respectively. In thyroidectomized rats treated with low doses of T₄, somatotrophs and thyrotrophs in mitosis increased to 38·4% and 80% respectively and, with simultaneous administration of a low dose of T₄ plus TRH, although less effective than T₄ alone, mitosis increased in somatotrophs and thyrotrophs to 11·1% and 54·5% respectively. A high dose of T₄ alone did not increase the mitotic figures in somatotrophs (38·8%), while it diminished the percentage of thyrotrophs to 25%. The administration of high doses of T₄ plus TRH had an opposite effect on the mitotic figures of somatotrophs and thyrotrophs and thus the percentage of somatotrophs increased to 50% while thyrotrophs decreased to 5·5%. Ten days of treatment with T₄ were insufficient to reverse the histology to euthyroidism. It can be concluded that in long-standing hypothyroidism: (1) thyroid hormone replacement elicits a dose-dependent and differential proliferative response on pituitary thyrotrophs and somatotrophs, (2) TRH is devoid of mitogenic effects when administered alone and (3) the proliferative response of somatotrophs to T₄ is enhanced by its co-administration with TRH, suggesting a permissive and/or synergistic effect of the thyroid hormone and TRH.

Journal of Endocrinology (1997) 154, 149–153

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