Thyrotropin-releasing hormone axonal varicosities appear to innervate dopaminergic neurons in the human hypothalamus.

Abstract

Thyrotropin-releasing hormone (TRH) has a critical role in the central regulation of thyroid-stimulating hormone (TSH) from the anterior pituitary, and subsequently, thyroid hormone secretion from the thyroid gland. In addition to its role in the regulation of HPT axis, TRH is a potent regulator of prolactin (PRL) secretion by stimulating PRL secretion either directly from lactotrophs or indirectly via its action on the tuberoinfundibular dopamine (TIDA) neurons. In rodents, the TRH neurons which regulate TSH and thyroid hormone secretion, called hypophysiotropic TRH neurons, are in the medial subdivision of the parvicellular paraventricular nucleus (PVN). In humans, the PVN also contains a large population of TRH neurons, especially in its medial part, but the location of hypophysiotropic TRH neurons is not yet known. In addition to regulating TSH and PRL secretion, TRH also functions as a neurotransmitter/neuromodulator. In rodents and teleosts, TRH axons densely innervate TIDA neurons to inhibit tyrosine hydroxylase (TH) biosynthesis, neuronal firing, and dopamine turnover which may contribute to increasing PRL secretion. No such connections have been reported in humans, although dopaminergic neurons express TRH receptors and TRH also regulates PRL secretion. The objectives of this study were to map TRH-IR and TH-IR structures in the human hypothalamus with single-label light microscopic immunocytochemistry and study their interaction with double-label light microscopic immunocytochemistry. We show that TRH-IR nerve terminals densely surround TH-IR neurons (perikarya and dendrites) in the infundibulum of the human hypothalamus. The micrographs illustrating these juxtapositions were taken by Olympus BX45 microscope equipped with a digital camera and with 100X oil immersion objective. Composite images were created from the consecutive micrographs if the neurons were larger than the frame of the camera, using Adobe Photoshop software. As no gaps between TRH-IR and TH-IR elements were seen, these contacts may be functional synapses by which TRH regulates the activity of dopaminergic neurons and subsequently TSH and PRL secretion.