An Overview of the Neuroendocrine Control of TSH and PRL, TSH Biosynthesis, Pituitary Deiodinase, and TSH-Producing Tumors

Abstract

The association of hypothyroidism and hyperprolactinemia has been known for many years and suggested that the abnormally elevated PRL levels in primary hypothyroidism might result from a decreased hypothalamic dopamine (DA) secretion rather than increased TRH stimulation, reflecting a general action of thyroid hormones on hypothalamic DA activity (1,2). The same mechanism is probably present in hypothalamic hypothyroidism defined by exaggerated and/or delayed TSH response to TRH, with reduced biological activity as suggested by the decreased T3 response to endogenous TSH released, probably dependent on alterations on its carbohydrate moiety, since it was demonstrated that TRH (decreased in central hypothyroidism) regulates TSH glycosylation (3). Furthermore, patients with hypothalamic hypothyroidism have an excess of s-TSH (4), reflecting an alteration in the combining properties of TSH subunits which may result from the abnormal glycosylation (3). As can be seen in Fig. 1, the greatly increased PRL levels were corrected by thyroid replacement. Besides, a decrease in hypothalamic and/or pituitary DA content or activity would be associated with decreased response to DA receptor blocking drugs such as chlorpromazine, metoclopramide, and domperidone. In effect, in patients with primary hypothyroidism and slight increase in basal PRL, we have shown a significantly lower increment in serum PRL after chlorpromazine when compared to normals (unpublished data). Scanlon and co-workers demonstrated that after the administration of metoclopramide (1) or domperidone (5), there was a significant release of TSH in euthyroid and subclinical hypothyroid patients, but not in those with overt hypothyroidism who lack DA inhibition of TSH release but may show marked DA inhibition of PRL secretion. It is then possible that thyroid hormones regulate hypothalamic DA either by enhancing DA secretion or by modulating DA receptors on the thyrotroph, the last possibility being the most likely. Therefore, thyroid hormones act directly on the thyrotrophs, inhibiting TSH secretion and stimulating hypothalamic DA secretion which acts as an intermediate step in the inhibition of TSH release (2). The stimulation of hypothalamic DA by thyroid hormones also inhibits PRL secretion by lactotrophs (2). Thus, it appears that thyroid hormones modulate the DA inhibitory tonus on the thyrotroph.