Hypophysiotropic thyrotropin-releasing hormone-synthesizing neurons in the human hypothalamus are innervated by neuropeptide Y, agouti-related protein, and alpha-melanocyte-stimulating hormone.
We recently demonstrated that three arcuate nucleus-derived peptides, neuropeptide Y (NPY), agouti-related protein (AGRP), and alphaMSH, are contained in axon terminals that heavily innervate hypophysiotropic TRH neurons in the rat brain and may contribute to the altered set-point of the hypothalamo-pituitary-thyroid axis during fasting. To determine whether a similar regulatory system exists in human brain, we performed a series of immunohistochemical studies using antisera against NPY, AGRP, alphaMSH, and TRH in adult hypothalami obtained within 15 h of death. Numerous small to medium-sized, fusiform and multipolar NPY-, AGRP-, and alphaMSH-immunoreactive (-IR) cells were widely distributed throughout the rostro-caudal extent of the infundibular (arcuate) nucleus. A similar distribution pattern was found for NPY- and AGRP-IR neurons in the arcuate nucleus, whereas alphaMSH-IR cells appeared to form a separate cell population. By double labeling fluorescent immunohistochemistry, 82% of NPY neurons cocontained AGRP, and 87% of AGRP neurons coexpressed NPY. No colocalization was found between alphaMSH- and AGRP-IR neurons. NPY-, AGRP-, and alphaMSH-containing axons densely innervated the hypothalamic paraventricular nucleus and were found in close juxtaposition to TRH-synthesizing cell bodies and dendrites. These studies demonstrate that in man, the NPY-, AGRP-, and alphaMSH-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 hypothalamo-pituitary-thyroid axis in the human brain.
Mihály
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Tupper Research Institute and Department of Medicine, New England Medical Center, Boston, Massachusetts 02111, USA.
Fekete
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Tatro
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Liposits
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Stopa
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Lechan
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RM
D000328:Adult; D054369:Agouti-Related Protein; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D011506:Proteins / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000096:biosynthesis*; D000521:alpha-MSH / Q000502:physiology*
C515198:AGRP protein, human; C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D011506:Proteins; D000521:alpha-MSH; D013973:Thyrotropin-Releasing Hormone