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To examine thyroid hormone regulation of the pituitary receptor for hypothalamic growth hormone (GH)-releasing factor (GRF), we studied effects of hypothyroidism on the pituitary GRF receptor (GRF-R) mRNA and its related parameters in rats. Thyroidectomy (Tx) induced a 61-65% reduction in GRF-R mRNA levels, which was significantly reversed with thyroxine (T4) replacement for 5 days at a dose of 1 microgram/100 g/day. Pituitary GH contents changed parallel to GRF-R mRNA levels following the Tx and T4 replacement. In contrast, Tx enhanced GRF release > 2 fold, which was not reversed with the regime of T4 replacement. These results indicate that thyroid hormone promotes pituitary GRF-R gene expression, not by modulating GRF secretion, but by acting on the pituitary directly. The decline in GRF receptor expression would contribute to somatotroph failure by rendering the pituitary refractory to the increased GRF signal in hypothyroidism.
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