A study of pituitary thyrotropin, its subunits, and messenger ribonucleic acids in nonthyroidal illness

Abstract

We studied serum TSH, pituitary TSH and α and β-subunits of TSH and their messenger ribonucleic acids (mRNAs) in three models of nonthyroidal illness (NTI) in the rat, ie diabetes mellitus (1 wk after 65 μg streptozotocin/g BW IP), turpentine oil-injection (8 to 48 hours after after a dose of 5 μl/g bw SC), and complete fasting for 72 hours. Euthyroid, hypothyroid (two months after thyroidectomy) and hyperthyroid rats (30 μgT 4/d × 7, SC) were also studied for comparison. Pituitary TSH, α and β subunits and serum TSH, T 4, and T 3 were measured by RIA. Pituitary mRNAs coding for common δ and TSH-β subunits were determined by cytoplasmic dot hybridization technique using specific [ 32P]-cDNA probes. In all NTI models there were significant decreases in serum levels of TSH, T 4, and T 3, but no significant changes were observed in the pituitary content of TSH, and α and TSH-β subunits. Hypothyroid rats had an increase in serum TSH, pituitary TSH, and pituitary TSH-β subunit and a decrease in pituitary α subunit. On the other hand, hyperthyroid rats showed a decrease in serum TSH, pituitary TSH, and pituitary TSH-β subunit, while there was no change in the α subunit. A significant reduction in the pituitary TSH-β mRNA levels was observed in all NT1 models and hyperthyroidism, while TSH-β mRNA was increased in thyroidectomized rats. α-mRNA was increased only in the pituitary of hypothyroid rats; there was no appreciable change in the pituitary α-mRNA in the various other pituitary groups. The kinetics of changes were studied in turpentine oil-injected rats and showed a significant reduction in serum TSH at four and eight hours after the injection, whereas TSH-β mRNA levels were decreased significantly at eight hours but not at 12 hours or later. We also studied 5′-monodeiodination of 126I-T 4 (to T 3) in pituitaries of all three experimental models and control rats; there was no significant difference. Our data suggest that NTI is associated with a decrease in the pituitary content of the mRNA for TSH-β subunit that may be transient and may contribute to fall in serum TSH in chronic NTI. Since pituitary TSH content was normal, a reduction in TSH release may be a more important factor than reduced TSH biosynthesis in determining fall in serum TSH at an early stage of NTI. Low serum TSH in NTI is not a result of an increase in the conversion of T 4 to T 3 in the pituitary.