Thyrotropin

Resistance to TSH is a syndrome of reduced sensitivity to a biologically active TSH molecule. Subjects have elevated TSH levels but no goiter. However, thyroid hormone concentration may vary from normal to very high, depending on the severity of the resistance. Individuals with very high TSH, low T4 and hypoplastic thyroid glands can be mistakenly diagnosed as having primary hypothyroidism due to a defective development of the thyroid gland. Those with normal or slightly decreased T4 can be misdiagnosed as having central hypothyroidism especially if their serum TSH concentration is only slightly elevated. Mutations in the TSH receptor (TSHr) gene have been reported in 16 families with homozygous or compound heterozygous inheritance. The mutant TSHrs show reduced or no function due to either altered ligand binding or defect in membrane targeting. Some individuals, heretozygous for a TSHr gene mutation can present mild resistance to TSH manifesting as euthyroidism with slight hyperthyrotropinemia. A larger proportion of families express the phenotype of resistance to TSH in the absence of a TSHr defect. In many the inheritance is dominant and the genetic cause has not been yet determined.

Thyrotropin (TSH), a pituitary glycoprotein hormone that stimulates the thyroid gland, has been cloned and sequenced from over a dozen teleost fish species. Although TSH is established as a primary driver of systemic thyroid status in mammals, its importance in the regulation of fish thyroid function is still uncertain. We review recent studies indicating that TSH structure is highly conserved across species representing six teleost families. These studies have found TSH messenger RNA consistently expressed in teleost pituitary tissue, although ectopic expression, particularly in gonads, has also been observed. They have also provided evidence for negative feedback inhibition of TSH expression by thyroid hormones, as well as stimulation by hypothalamic peptides. Descriptive studies have found increased TSHbeta expression associated with life history events thought to be promoted by thyroid hormones. These results, coupled with the discovery of a G-protein coupled TSH receptor in several teleost species, supports an active and conserved role for TSH in the regulation of teleost thyroid function. The relative importance of central pathways in regulating thyroid hormone provision to targets and the identity of a proposed thyrotropin-inhibiting factor in teleost fish are still unanswered questions whose resolution will be facilitated by development of methods to measure circulating TSH and its secretion from the pituitary gland.