TRH is a tripeptide amide that functions as a neurotransmitter but also serves as
a neurohormone that has a critical role in the central regulation of the hypothalamic-pituitary-thyroid
axis. Hypophysiotropic TRH neurons involved in this neuroendocrine process are located
in the hypothalamic paraventricular nucleus and secrete TRH into the pericapillary
space of the external zone of the median eminence for conveyance to anterior pituitary
thyrotrophs. Under basal conditions, the activity of hypophysiotropic TRH neurons
is regulated by the negative feedback effects of thyroid hormone to ensure stable,
circulating, thyroid hormone concentrations, a mechanism that involves complex interactions
between hypophysiotropic TRH neurons and the vascular system, cerebrospinal fluid,
and specialized glial cells called tanycytes. Hypophysiotropic TRH neurons also integrate
other humoral and neuronal inputs that can alter the setpoint for negative feedback
regulation by thyroid hormone. This mechanism facilitates adaptation of the organism
to changing environmental conditions, including the shortage of food and a cold environment.
The thyroid axis is also affected by other adverse conditions such as infection, but
the central mechanisms mediating suppression of hypophysiotropic TRH may be pathophysiological.
In this review, we discuss current knowledge about the mechanisms that contribute
to the regulation of hypophysiotropic TRH neurons under physiological and pathophysiological
conditions.
