Effect of Hypothyroidism and Thyroxine Replacement on Growth Hormone in the Rat*

Abstract

Thyroidectomy is known to decrease the amount of GH in the pituitary and serum of rats. The present experiments were undertaken to assess GH levels in the serum of thyroidectomized (Tx) rats using RIA and biological criteria simultaneously. In addition to its ability to sustain growth, the biological activity of circulating GH was assessed by measuring its ability to induce refractoriness to the early insulin-like response of epididymal fat to a test dose of GH added in vitro. This paradoxical desensitization of tissue to some of its own actions constitutes a highly specific and sensitive biological index of GH action. Serum concentrations of T₄ declined rapidly after Tx and reached barely detactable levels by the 4th postoperative day. Pituitary concentrations of GH remained unchanged through the 4th postoperative day. Pituitary concentrations of GH remained unchanged through the 4th postoperative day and thereafter declined slowly, reaching 50% of control values by the 7th day and 15% by the 10th day and becoming barely detectable by the 14th day. In contrast, serum concentrations of GH remained within the normal range (40–100 ng/ml) for 10 days after thyroidectomy, but in one experiment, the mean value on the 10th postoperative day was significantly lower than that found in the control group studied simultaneously. By the 14th postoperative day, however, serum levels of GH were markedly reduced (approximately 20 ng/ml) but remained well within the detectable range. Growth significantly slowed between the 2nd and 6th days and virtually ceased by the 10th day even though serum levels of GH were still in the normal range. Epididymal fat remained insensitive to the insulin-like action of GH through the 7th day, indicating that circulating levels of GH were sufficiently high to maintain refractoriness. By the 10th day, a small insulinlike response was evident. This response nearly doubled by the 14th day despite the continued presence of GH in plasma. Administration of GH (2 μg/100 g) to Tx rats 3 h before sacrifice induced refractoriness, confirming that chronically Tx rats can respond to this effect of GH. Administration of T₄ 24 h before sacrifice to 14-day Tx rats increased pituitary and serum concentrations of GH and induced refractoriness. T4 administration failed to induce refractoriness in the absence of the pituitary. These data suggest that after thyroidectomy, plasma concentrations of GH can be maintained at normal or near-normal levels until pituitary reserves are depleted. Failure of growth results even when serum GH is still in the normal range, probably from lack of the synergistic effects of T₄. Loss of refractoriness to the insulin-like effects of GH more nearly reflects the physiological activity of circulating GH than does body growth.