Hypophysiotropic thyrotropin-releasing hormone-synthesizing neurons in thehuman hypothalamus are innervated by neuropeptide Y, agouti-related protein, and alpha-melanocyte-stimulating hormone

We recently demonstrated that three arcuate nucleus-derived peptides, neuro peptide Y (NPY), agouti-related protein (AGRP), and alpha MSH, are containe d in axon terminals that heavily innervate hypophysiotropic TRH neurons in the rat brain and may contribute to the altered set-point of the hypothalam o-pituitary-thyroid axis during fasting. To determine whether a similar reg ulatory system exists in human brain, we performed a series of immunohistoc hemical studies using antisera against NPY, AGRP, alpha MSH, and TRH in adu lt hypothalami obtained within 15 h of death. Numerous small to medium-size d, fusiform and multipolar NPY-, AGRP-, and alpha MSH-immunoreactive (-IR) cells were widely distributed throughout the rostro-caudal extent of the in fundibular (arcuate) nucleus. A similar distribution pattern was found for NPY- and AGRP-IR neurons in the arcuate nucleus, whereas alpha MSH-IR cells appeared to form a separate cell population. By double labeling fluorescen t immunohistochemistry, 82% of NPY neurons cocontained AGRP, and 87% of AGR P neurons coexpressed NPY. No colocalization was found between alpha MSH-an d AGRP-IR neurons. NPY-, AGRP-, and alpha MSH-containing axons densely inne rvated the hypothalamic paraventricular nucleus and were found in close jux taposition to TRH-synthesizing cell bodies and dendrites. These studies dem onstrate that in man, the NPY-, AGRP-, and alpha MSK-IR neuronal systems in the infundibular and paraventricular nuclei are highly reminiscent of that observed in the rat and may similarly be involved in regulating the hypoth alamo-pituitary-thyroid axis in the human brain.