Inhibitory Effect of Adrenocorticotropin on Corticotropin-Releasing Factor Release From Rat Hypothalamus in Vitro

Suda, Toshio; Yajima, Fumiko; Tomori, Naoki; Sumitomo, Takashi; Nakagami, Yuriko; Ushiyama, Tsuyako; Demura, Hiroshi; Shizume, Kazuo

doi:10.1210/endo-118-1-459

Cited by 63 publications

(21 citation statements)

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“…ACTH also was shown to inhibit unstimulated iCRH secretion in a dose-dependent fashion in vitro. This inhibitory effect was partially retained (-60%) by a-MSH, but not by CLIP (12). Sl-EP has been shown to suppress ACTH and cortisol levels in normal subject (54) and to inhibit both corticotropin-releasing bioactivity (CRB) and iCRH secretion in vitro (55,56 Our results suggesting the presence of a long glucocorticoid-mediated negative feedback loop are consistent with studies conducted with similar or different experimental paradigms.…”

Section: Resultssupporting

confidence: 88%

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Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications.

Calogero¹,

Gallucci²,

Gold³

et al. 1988

J. Clin. Invest.

142

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To examine whether the hypothalamic corticotropin-releasing hormone (CRH) neuron is regulated by CRH, by products of the proopiomelanocortin (POMC) gene, and/or by glucocorticoids, we used a rat hypothalamic organ culture system in which rat CRH secretion from single explanted hypothalami was evaluated by an RIA (iCRH) specific for rat CRH. The effects of graded concentrations of ovine CRH (oCRH), adrenocorticotropin hormone (ACTH), 6-endorphin (f-EP), a-melanocyte-stimulating hormone (a-MSH), corticotropin-like intermediate lobe peptide (CLIP), ovine ft-lipotropin (ovine f-LPH), and dexamethasone (DEX) upon unstimulated and serotonin-(5HT), acetylcholine-(ACh), and norepinephrine-(NE) stimulated CRH secretion were determined. oCRH and DEX inhibited unstimulated iCRH secretion with ID50 at the 10-8 M range. ACTH had no detectable suppressive effect at 10-8 M. oCRH, ACTH, and DEX inhibited 5HT-, ACh-, and NE-stimulated iCRH secretion in a dose-dependent fashion.SEEP, a-MSH, and CLIP also inhibited 5HT-induced iCRH secretion. Of the latter peptides, the strongest inhibitor was f-EP and the weakest was CLIP. Ovine fi-LPH had only a weak inhibitory effect on 5HT-induced iCRH secretion. Generally, the concentrations required for 50% suppression of neurotransmitter-stimulated iCRH secretion were significantly lower than those required for a similar suppression of unstimulated iCRH secretion.In conclusion, these data suggest the presence of multiple negative feedback loops involved in the regulation of the hypothalamic CRH neuron: an ultrashort CRH-mediated loop, a short, hypothalamic POMC-derived peptide loop, and a long, glucocorticoid-mediated negative feedback loop. The potency of these negative feedback loops may be determined by the state of activation of the CRH neuron.

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Section: Resultssupporting

confidence: 88%

“…This type ofcontrol, however, could not be demonstrated in dispersed rat anterior pituicyte cultures (1 1). The presence, on the other hand, of a short-loop negative feedback effect of ACTH on hypothalamic CRH secretion has been recently suggested ( 12,13).…”

Section: Introductionmentioning

confidence: 99%

Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications.

Calogero¹,

Gallucci²,

Gold³

et al. 1988

J. Clin. Invest.

142

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“…The distribution of MC3-R mRNA in the arcuate nucleus as well as terminal fields of arcuate neurons implies that melanocortin peptides produced in the hypothalamus may function as neuromodulators and neurotransmitters. The distribution of MC3-R mRNA in the brain is also interesting in light of the postulated role of melanocortin peptides in neuroendocrine (26)(27)(28), cardiovascular (8,9), and thermoregulatory functions (4,5 rostral and medial parts ofthe medial preoptic area and in the arcuate and posterior periventricular hypothalamic nuclei, which mediate various cardiovascular and neuroendocrine processes (29). Furthermore, the posterior nucleus of the hypothalamus and the lateral preoptic and lateral hypotha- lamic areas all contained MC3-R mRNA-containing neurons and are thought to play key roles in coordinating thermoregulatory responses (30).…”

Section: (Intelligenetics)mentioning

confidence: 99%

Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system.

Roselli-Rehfuss

Mountjoy

Robbins

et al. 1993

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

652

466

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Corticotropin (ACTH) and melanotropin (MSH) peptides (melanocortins) are produced not only in the pituitary but also in the brain, with highest concentrations in the arcuate nudeus of the hypothalamus and the commisural nucleus of the solitary tract. We have identified a receptor for MSH and ACTH peptides that is specdflcally expressed in regions of the hypothalamus and limbic system. This melanocortin receptor (MC3-R) is found in neurons of the arcuate nucleus known to express proopiomelanocortin (POMC) and in a subset of the nuclei to which these neurons send projections.The MC3-R is 43% identical to the MSH receptor present in melanocytes and is strongly coupled to adenylyl cyclase. Unlike the MSH or ACTH receptors, MC3-R is potendy activated by 'yMSH peptides, POMC products that were named for their amino acid homology with a-and f-MSH, but lack melanotropic activity. The primary biological role of the yMSH peptides is not yet understood. The location and properties of this receptor provide a pharmacological basis for the action of POMC peptides produced in the brain and possibly a specific physiological role for -MSH.The large proopiomelanocortin (POMC) protein is processed into three main families ofpeptides with adrenocorticotropic, melanotropic, or opiate activities. The melanocortins, which include all POMC peptides except (3-endorphin, are primarily known for their role in the regulation of adrenal steroid production [corticotropin (ACTH)] and pigmentation [a melanotropin (a-MSH)]. In addition to these well-known effects, administration of melanocortin peptides has been reported to increase retention of learned behaviors (1, 2), induce grooming behavior (3), decrease fever (4, 5), stimulate nerve regeneration (6, 7), and increase heart rate, blood pressure, and natriuresis (8, 9). Many ofthese biological activities have been demonstrated to result from direct action of the melanocortin peptides in the brain.Recently, the cloning of the MSH (10, 11) and ACTH receptors (10) (MSH-R and ACTH-R) has provided probes for the examination of MSH-R and ACTH-R mRNA expression. Thus far, MSH-R and ACTH-R mRNA expression has only been detected in melanocytes and in the adrenal cortex, respectively. Although specific high-affinity MSH and ACTH binding has been reported in brain, with highest levels in the hypothalamus (12, 13), no MSH-R or ACTH-R mRNA was detected in the brain by either Northern hybridization or in situ hybridization (14,15). Additionally, melanocortin binding and biological action in the brain display pharmacological profiles that do not match those of either the adrenal The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.ACTH-R or the melanocyte MSH-R. These data suggested the existence of unique melanocortin receptor(s) expressed specifically in the brain.We report here the cloning and characterization of a neural-specific melanocorti...

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“…Melanocortin peptides have been demonstrated, for example, to inhibit CRH release in hypothalamic culture systems [6, 7]. Central administration of melanocortin peptides has been demonstrated to activate the HPA axis, and increase circulating ACTH and corticosterone levels in the rat [8, 9].…”

Section: Introductionmentioning

confidence: 99%

Disproportionate Inhibition of Feeding in <i>A<sup>y</sup></i> Mice by Certain Stressors: A Cautionary Note

Souza

Butler

Cone³

2000

Neuroendocrinology

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A study of the effects of insulin-induced hypoglycemia in the obese yellow agouti A^y mouse was initiated to test the hypothesis that the central melanocortin pathways are required for a normal sympathetic response to hypoglycemia. An experimental protocol was performed in which young nonobese male mice were isolated and fasted beginning on day 1, then tested for glucose responses to insulin-induced hypoglycemia on day 2. Normal mice demonstrated the expected glucose rebound to hypoglycemia, exceeding baseline glucose levels by 2–3 times as a consequence of increased gluconeogenesis and glycogenolysis before returning to baseline levels. A^y animals lacked the rebound, exhibiting instead a gradual restoration of baseline glucose levels. The results suggested a defective sympathetic response to hypoglycemia in the A^y mouse. However, a more detailed analysis demonstrated that the lack of a hyperglycemic rebound was due to an acute inhibition of feeding specifically in the A^y mouse, which resulted not from the hypoglycemia stressor, but rather from the stress of isolation. Handling and intraperitoneal administration of saline also specifically inhibited food intake in the A^y but not the wild-type mouse, while restraint stress had an equivalent inhibitory effect on food intake on wild-type and A^y mice. Since the A^y mouse has defective hypothalamic melanocortin-4 receptor (MC4-R) signaling, these data imply that the central melanocortin pathway is necessary for regulating the effects of stress on feeding behavior. Furthermore, these data demonstrate the need for exercising extreme caution in designing experiments to analyze feeding behavior and metabolism in genetic or pharmacological models involving perturbation of the melanocortin system.

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Inhibitory Effect of Adrenocorticotropin on Corticotropin-Releasing Factor Release From Rat Hypothalamus in Vitro

Cited by 63 publications

References 0 publications

Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications.

Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications.

Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system.

Disproportionate Inhibition of Feeding in <i>A<sup>y</sup></i> Mice by Certain Stressors: A Cautionary Note

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