PT - JOURNAL ARTICLE AU - Fekete, Csaba AU - Mihály, Emese AU - Luo, Lu-Guang AU - Kelly, Joseph AU - Clausen, Jes Thorn AU - Mao, QuanFu AU - Rand, William M. AU - Moss, Larry Gene AU - Kuhar, Michael AU - Emerson, Charles H. AU - Jackson, Ivor M. D. AU - Lechan, Ronald M. TI - Association of Cocaine- and Amphetamine-Regulated Transcript-Immunoreactive Elements with Thyrotropin-Releasing Hormone-Synthesizing Neurons in the Hypothalamic Paraventricular Nucleus and Its Role in the Regulation of the Hypothalamic–Pituitary–Thyroid Axis during Fasting AID - 10.1523/JNEUROSCI.20-24-09224.2000 DP - 2000 Dec 15 TA - The Journal of Neuroscience PG - 9224--9234 VI - 20 IP - 24 4099 - http://www.jneurosci.org/content/20/24/9224.short 4100 - http://www.jneurosci.org/content/20/24/9224.full SO - J. Neurosci.2000 Dec 15; 20 AB - Because cocaine- and amphetamine-regulated transcript (CART) coexists with α-melanocyte stimulating hormone (α-MSH) in the arcuate nucleus neurons and we have recently demonstrated that α-MSH innervates TRH-synthesizing neurons in the hypothalamic paraventricular nucleus (PVN), we raised the possibility that CART may also be contained in fibers that innervate hypophysiotropic thyrotropin-releasing hormone (TRH) neurons and modulate TRH gene expression. Triple-labeling fluorescent in situhybridization and immunofluorescence were performed to reveal the morphological relationships between pro-TRH mRNA-containing neurons and CART- and α-MSH-immunoreactive (IR) axons. CART-IR axons densely innervated the majority of pro-TRH mRNA-containing neurons in all parvocellular subdivisions of the PVN and established asymmetric synaptic specializations with pro-TRH neurons. However, whereas all α-MSH-IR axons in the PVN contained CART-IR, only a portion of CART-IR axons in contact with pro-TRH neurons were immunoreactive for α-MSH. In the medial and periventricular parvocellular subdivisions of the PVN, CART was co-contained in ∼80% of pro-TRH neuronal perikarya, whereas colocalization with pro-TRH was found in <10% of the anterior parvocellular subdivision neurons. In addition, >80% of TRH/CART neurons in the periventricular and medial parvocellular subdivisions accumulated Fluoro-Gold after systemic administration, suggesting that CART may serve as a marker for hypophysiotropic TRH neurons. CART prevented fasting-induced suppression of pro-TRH in the PVN when administered intracerebroventricularly and increased the content of TRH in hypothalamic cell cultures. These studies establish an anatomical association between CART and pro-TRH-producing neurons in the PVN and demonstrate that CART has a stimulatory effect on hypophysiotropic TRH neurons by increasing pro-TRH gene expression and the biosynthesis of TRH.