The Ups and Downs of Thyrotropin-Releasing Hormone

Abstract

The synthesis and secretion of thyrotropin-releasing hormone (TRH) is absolutely required for intact thyroid function in humans and rodents. Furthermore, feedback regulation of TRH production by thyroid hormone allows for tight maintenance of circulating thyroid hormone levels and thus establishes the hypothalamic-pituitary-thyroid (H-P-T) axis. Although the TRH gene is expressed in many regions of the brain, its regulation by thyroid hormone is restricted to neurons in the paraventricular nucleus of the hypothalamus (PVH) (1). This discrete set of neurons in the PVH, termed hypophysiotropic, project to the median eminence where mature TRH peptide is released into the portal capillary system bound for TRH-receptors present in the anterior pituitary (Fig. 1​1).). Whereas it is clear that thyroid hormone regulates TRH production in the PVH both at the level of gene expression and posttranslational processing, in this issue of Endocrinology, Sanchez et al. (2) provide evidence that thyroid hormone also controls TRH peptide degradation by regulating the enzyme pyroglutamyl peptidase II (PPII). This enzyme is expressed in tanycytes; glial cells that line the third ventricle in the hypothalamus whose cytoplasmic processes extend into the median eminence. Thus, PPII appears to regulate TRH peptide bioavailability upstream of the pituitary.