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

Csaba Fekete, E. Mihály, Lu Guang Luo, Joseph Kelly, Jes Thorn Clausen, QuanFu Mao, William M. Rand, Larry Gene Moss, Michael Kuhar, Charles H. Emerson, Ivor M D Jackson, Ronald M. Lechan

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Abstract

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 situ hybridization 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 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.

Original languageEnglish
Pages (from-to)9224-9234
Number of pages11
JournalJournal of Neuroscience
Volume20
Issue number24
Publication statusPublished - Dec 15 2000

Fingerprint

Thyrotropin-Releasing Hormone
Paraventricular Hypothalamic Nucleus
Amphetamine
Cocaine
Fasting
Thyroid Gland
Neurons
Melanocyte-Stimulating Hormones
Pituitary Hormone-Releasing Hormones
Axons
Gene Expression
pro-thyrotropin releasing hormone
Messenger RNA
Arcuate Nucleus of Hypothalamus
Fluorescence In Situ Hybridization
Fluorescent Antibody Technique
Cell Culture Techniques

Keywords

  • α-MSH
  • CART
  • Fasting
  • Leptin
  • Thyroid axis
  • Thyrotropin-releasing hormone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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. / Fekete, Csaba; Mihály, E.; Luo, Lu Guang; Kelly, Joseph; Clausen, Jes Thorn; Mao, QuanFu; Rand, William M.; Moss, Larry Gene; Kuhar, Michael; Emerson, Charles H.; Jackson, Ivor M D; Lechan, Ronald M.

In: Journal of Neuroscience, Vol. 20, No. 24, 15.12.2000, p. 9224-9234.

Research output: Contribution to journalArticle

Fekete, Csaba ; Mihály, E. ; Luo, Lu Guang ; Kelly, Joseph ; Clausen, Jes Thorn ; Mao, QuanFu ; Rand, William M. ; Moss, Larry Gene ; Kuhar, Michael ; Emerson, Charles H. ; Jackson, Ivor M D ; Lechan, Ronald M. / 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. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 24. pp. 9224-9234.
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abstract = "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 situ hybridization 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 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.",
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AU - Fekete, Csaba

AU - Mihály, E.

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.

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