Immunocytochemical localization of ACTH perikarya in nucleus tractus solitarius: evidence for a second opiocortin neuronal system

Joseph, Shirley A.; Pilcher, Webster H.; Bennett‐Clarke, Carol A.

doi:10.1016/0304-3940(83)90372-5

Cited by 166 publications

(67 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data are consistent with previous light microscopic findings that ACTH, also a post-translational cleavage product of POMC, is contained in axons adjacent to TRH neurons in the PVN (Liao et al, 1991). Although ␣-MSH is synthesized in two regions within the brain, the arcuate nucleus and the nucleus tractus solitarius (Dube et al, 1978;Joseph et al, 1983), the arcuate nucleus is probably the only source of ␣-MSHcontaining fibers in the PVN. Deafferentation of the mediobasal hypothalamus that separates the arcuate nucleus from the rest of the brain results in marked depletion of ␣-MSH in the dorsal hypothalamus (Eskay et al, 1979), whereas nearly half of the POMC-synthesizing neurons in the arcuate nucleus are labeled by the retrograde transport of marker substances injected into the PVN (Sawchenko et al, 1982).…”

Section: Discussionsupporting

confidence: 92%

α-Melanocyte-Stimulating Hormone Is Contained in Nerve Terminals Innervating Thyrotropin-Releasing Hormone-Synthesizing Neurons in the Hypothalamic Paraventricular Nucleus and Prevents Fasting-Induced Suppression of Prothyrotropin-Releasing Hormone Gene Expression

et al. 2000

View full text Add to dashboard Cite

The hypothalamic arcuate nucleus has an essential role in mediating the homeostatic responses of the thyroid axis to fasting by altering the sensitivity of prothyrotropin-releasing hormone (pro-TRH) gene expression in the paraventricular nucleus (PVN) to feedback regulation by thyroid hormone. Because agouti-related protein (AGRP), a leptin-regulated, arcuate nucleus-derived peptide with ␣-MSH antagonist activity, is contained in axon terminals that terminate on TRH neurons in the PVN, we raised the possibility that ␣-MSH may also participate in the mechanism by which leptin influences pro-TRH gene expression. By double-labeling immunocytochemistry, ␣-MSH-IR axon varicosities were juxtaposed to ϳ70% of pro-TRH neurons in the anterior and periventricular parvocellular subdivisions of the PVN and to 34% of pro-TRH neurons in the medial parvocellular subdivision, establishing synaptic contacts both on the cell soma and dendrites. All pro-TRH neurons receiving contacts by ␣-MSH-containing fibers also were innervated by axons containing AGRP. The intracerebroventricular infusion of 300 ng of ␣-MSH every 6 hr for 3 d prevented fasting-induced suppression of pro-TRH in the PVN but had no effect on AGRP mRNA in the arcuate nucleus. ␣-MSH also increased circulating levels of free thyroxine (T4) 2.5-fold over the levels in fasted controls, but free T4 did not reach the levels in fed controls. These data suggest that ␣-MSH has an important role in the activation of pro-TRH gene expression in hypophysiotropic neurons via either a mono-and/or multisynaptic pathway to the PVN, but factors in addition to ␣-MSH also contribute to the mechanism by which leptin administration restores thyroid hormone levels to normal in fasted animals.

show abstract

Section: Discussionsupporting

confidence: 92%

α-Melanocyte-Stimulating Hormone Is Contained in Nerve Terminals Innervating Thyrotropin-Releasing Hormone-Synthesizing Neurons in the Hypothalamic Paraventricular Nucleus and Prevents Fasting-Induced Suppression of Prothyrotropin-Releasing Hormone Gene Expression

et al. 2000

View full text Add to dashboard Cite

show abstract

“…A small population of the EGFP neurons was also found in the AP itself. This distribution of EGFP neurons is similar to immunohistochemically identified POMC neurons in the rat brainstem (Joseph et al, 1983;Schwartzberg and Nakane, 1983;Bronstein et al, 1992). The bright fluorescence made POMC-EGFP neurons easily identifiable for recording ( Fig.…”

Section: Resultssupporting

confidence: 78%

Proopiomelanocortin Neurons in Nucleus Tractus Solitarius Are Activated by Visceral Afferents: Regulation by Cholecystokinin and Opioids

et al. 2005

View full text Add to dashboard Cite

show abstract

“…The experiments described here suggest that the dysregulation within the caudal brainstem is responsible for consummatory deficit that occurs after ablation of AgRP neurons in the adult mouse, but it is unclear whether the dysregulation is due to the loss of direct AgRP neuron inputs to brainstem nuclei or to indirect effects mediated by the dysregulation in forebrain regions. Neuroanatomical studies indicate that hypothalamic POMC neurons directly innervate a few brainstem regions, including the NTS (47), and there is a local population of POMC-expressing neurons in the NTS (1,48). Despite these indications that the NTS is an important site of melanocortin signaling, our results suggest that blockade of melanocortin signaling with agouti protein is insufficient to overcome the effects of AgRP neuron ablation.…”

Section: Discussionmentioning

confidence: 66%

Starvation after AgRP neuron ablation is independent of melanocortin signaling

Howell

Cowley

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

106

View full text Add to dashboard Cite

Ablation of inhibitory agouti-related protein (AgRP)-expressing neurons in the arcuate nucleus that also synthesize ␥-aminobutyric acid (GABA) and neuropeptide Y in adult mice leads to starvation within 1 week. The removal of inhibition from the AgRP neurons onto neighboring proopiomelanocortin neurons and their common postsynaptic neurons is predicted to stimulate melanocortin signaling, which is known to inhibit appetite. To examine the importance of uncontrolled melanocortin signaling in mediating starvation in this model, we ablated AgRP neurons in A y /a mice that have chronic blockade of the melanocortin signaling. The blockade of melanocortin signaling did not ameliorate the rate of starvation. On both WT and A y /a genetic backgrounds, there was a progressive decrease in meal frequency after AgRP neuron ablation. Surprisingly, intraoral feeding also was dramatically reduced after the ablation of AgRP neurons. These results indicate that both the appetitive and consummatory aspects of feeding become impaired in a melanocortin-independent manner after AgRP neuron ablation.T he melanocortin signaling pathway in the medial hypothalamus has emerged as a critical mediator of hormonal and neuronal signals that regulate energy balance (1-3). Genetic, pharmacological, anatomical, and electrophysiological techniques have established a pivotal role for proopiomelanocortin (POMC) neurons in the arcuate (ARC) and their signaling via melanocortin (␣-MSH) to cells bearing melanocortin-4 receptors (MC4R) in the paraventricular nucleus (PVN) and other brain regions in the control of appetite and metabolism (1,4,5). Neighboring cells that coexpress neuropeptide Y (NPY) and agouti-related protein (AgRP) also have been implicated in appetite and energy balance because these peptides stimulate robust feeding when injected into the brain, and their mRNA levels increase in the ARC under starvation conditions, as well as in obese animals deficient in leptin signaling (2,(6)(7)(8). Various experiments suggest that NPY acts by inhibiting the activity of POMC neurons and postsynaptic MC4R-bearing cells by activating G␣i-coupled NPY Y1 and/or Y5 receptors (7, 9-12). The activation of these receptors is predicted to counteract melanocortin activation of G␣s-coupled MC4R. AgRP acts in concert with NPY by blocking the binding of ␣-MSH to MC4R (8,13,14). The neurons that make NPY and AgRP also produce GABA, which inhibits POMC neurons and probably MC4R-bearing cells (15,16). Thus, these AgRP neurons are poised to inhibit melanocortin signaling by the neighboring POMC cells.The activation of melanocortin signaling by leptin inhibits appetite while stimulating metabolism (1, 2, 6). Consequently, the inactivation of mouse genes encoding leptin, leptin receptor, POMC, or MC4R leads to obesity (17)(18)(19)(20). However, the inactivation of genes encoding NPY, AgRP, or both has little effect on energy balance (21-23). These genetic results suggest that compensatory mechanisms in the KO mice mask the normal role of these peptides. Nevertheles...

show abstract

Immunocytochemical localization of ACTH perikarya in nucleus tractus solitarius: evidence for a second opiocortin neuronal system

Cited by 166 publications

References 16 publications

α-Melanocyte-Stimulating Hormone Is Contained in Nerve Terminals Innervating Thyrotropin-Releasing Hormone-Synthesizing Neurons in the Hypothalamic Paraventricular Nucleus and Prevents Fasting-Induced Suppression of Prothyrotropin-Releasing Hormone Gene Expression

α-Melanocyte-Stimulating Hormone Is Contained in Nerve Terminals Innervating Thyrotropin-Releasing Hormone-Synthesizing Neurons in the Hypothalamic Paraventricular Nucleus and Prevents Fasting-Induced Suppression of Prothyrotropin-Releasing Hormone Gene Expression

Proopiomelanocortin Neurons in Nucleus Tractus Solitarius Are Activated by Visceral Afferents: Regulation by Cholecystokinin and Opioids

Starvation after AgRP neuron ablation is independent of melanocortin signaling

Contact Info

Product

Resources

About