Difference between Thyroidectomized and Hypophysectomized Animals in Their Hepatic Ribonucleic Acid Response to Thyroid Hormone*

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Abstract
Previous studies in rats have established that thyroidectomy leads to a 45% reduction in total cytoplasmic and polyadenylate-containing RNA which can be completely reversed by thyroid hormone administration. Since hypothyroidism is associated with a marked deficiency of circulating pituitary GH, we undertook a series of experiments to evaluate the potential role of GH in this process. Injection of thyroidectomized animals with 0.2 IU GH/100 g BW-day for 10 days, a dosesufficient to normalize the growth rate of hypophysectomized (Hypox) animals, resulted in a significant increase in hepatic RNA content but failed to normalize the levels to euthyroid values. Thus, the effects of T4 cannot be attributed exclusively to its ability to stimulate GH in thyroidectomized animals. This conclusion was confirmed by the results of studies carried out in Hypox animals treated either with GH, as described above, or with a replacement dose of T4 (1.5 μg/100 g BW). Each hormone produced a significant though limited increase in RNA. When administered together the net effect of both hormones appeared additive. Nevertheless, even combined administration restored the RNA content per mg DNA to only approximately 62% of the euthyroid control values. The incomplete RNA response to T4 in Hypox animals could not be attributed to a generalizedresistance to thyroid hormone, since T4 readily normalized the levels of hepatic mitochondrial a-glycerophosphate dehydrogenase and cytosolic malic enzyme. Moreover, there was no evidence of deficient T4 to T3 conversion or reduced nuclear binding. Simultaneous administration of dihydrotestosterone and corticosterone together with T4 and GH also failed to normalize the RNA content. The findings suggest that both GH and thyroid hormone are involved in maintaining normal hepatic RNA content and raise, among other explanations, the possibility that unidentified pituitary factors may be required for complete normalization of hepatic RNA content in Hypox animals. Differences between the response of hepatic RNA and marker enzymes to T4 in hypopituitary animals further emphasize the importance of postreceptor factors in thyroid hormone expression.