Agouti-related protein has an inhibitory paracrine role in the rat adrenal gland

Dhillo, Waljit S.; Small, C; Gardiner, James; Bewick, Gavin; Whitworth, E; Jethwa, Preeti H.; Seal, LJ; Ghatei, M.A.; Hinson, J. P.; Bloom, Stephen R.

doi:10.1016/s0006-291x(02)02991-1

Cited by 45 publications

(36 citation statements)

References 29 publications

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“…Of the 5 MCRs only the MC3R has been shown to have any significant affinity for γ-MSH (Gantz et al, 1993), although its role in mediating the effects of γ-MSH on HSL activity are contradicted by several pieces of evidence. Firstly, the mRNA expression profile of the MC3R is not the same as the binding profile described by Pedersen and Brownie, although expression of the MC3R has been reported in the rat adrenal (Dhillo et al, 2003). Secondly, ACTH is as potent an agonist at the MC3R as γ-MSH, which does not correlate with the low affinity for the Lys-γ3-MSH binding site described reported by Pedersen and Brownie.…”

Section: A Role For Lys-γ γ γ γ3-msh In Other Tissues?mentioning

confidence: 59%

Lys-gamma3-MSH: A global regulator of hormone sensitive lipase activity?

Bicknell

Harmer²,

Yiangson³

et al. 2009

Molecular and Cellular Endocrinology

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Section: A Role For Lys-γ γ γ γ3-msh In Other Tissues?mentioning

confidence: 59%

Lys-gamma3-MSH: A global regulator of hormone sensitive lipase activity?

Bicknell

Harmer²,

Yiangson³

et al. 2009

Molecular and Cellular Endocrinology

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“…Thus, a non-CRH-mediated mechanism leading to elevated basal corticosterone in the MC3-R −/− is possible also. In fact, it is possible that MC3-R deletion from the adrenal gland results in hypercorticosteronemia by eliminating the ability of AgRP to induce its paracrine inhibitory effects on corticosterone (20,44).…”

Section: Discussionmentioning

confidence: 99%

“…4B) did not differ in 10-mo-old WT and MC3-R −/− mice. Because MC3-R also is expressed in the adrenal gland, we hypothesized that deletion of MC3-R could affect adrenal ACTH sensitivity directly (20). We tested adrenal response to ACTH in vivo and ex vivo in an explant culture model.…”

Section: Mc3-r −/− Mice Exhibit Elevated Basal Corticosterone and Defmentioning

confidence: 99%

Melanocortin-3 receptor regulates the normal fasting response

Renquist

Murphy

Larson

et al. 2012

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

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The melanocortin-3 receptor-deficient (MC3-R −/− ) mouse exhibits mild obesity without hyperphagia or hypometabolism. MC3-R deletion is reported to increase adiposity, reduce lean mass and white adipose tissue inflammation, and increase sensitivity to salt-induced hypertension. We show here that the MC3-R −/− mouse exhibits defective fasting-induced white adipose tissue lipolysis, fasting-induced liver triglyceride accumulation, fasting-induced refeeding, and fasting-induced regulation of the adipostatic and hypothalamic-adrenal-pituitary axes. Close examination of the hypothalamic-pituitary-adrenal axis showed that MC3-R −/− mice exhibit elevated nadir corticosterone as well as a blunted fasting-induced activation of the axis. The previously described phenotypes of this animal and the reduced bone density reported here parallel those of Cushing syndrome. Thus, MC3-R is required for communicating nutritional status to both central and peripheral tissues involved in nutrient partitioning, and this defect explains much of the metabolic phenotype in the model. energy homeostasis | nonesterified fatty acid | corticotrophin-releasing hormone | hormone-sensitive lipase R esearch on the central melanocortin system has focused on the role of the melanocortin-4 receptor (MC4-R) in energy homeostasis, particularly as a result of the hyperphagic obesity syndrome found in both mice and humans with mutations in this receptor (1-3). A large body of work has demonstrated that circuitry regulated by the MC4-R is essential for much of leptin action and coordinates energy intake with energy expenditure to maintain long-term energy homeostasis (4). In contrast, the melanocortin-3 receptor (MC3-R), expressed in ∼35 different nuclei in the CNS with a pattern distinct from that of the MC4-R

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“…RNA was extracted from BAT using Tri-reagent (Helena Biosciences, Sunderland, UK) according to the manufacturer's protocol. Northern Blot analysis was performed as previously described [15]. The filter was exposed to phosphoscreen overnight prior to quantification of UCP-1 mRNA expression using ImageQuant software (GE Healthcare, Chalfont St Giles, UK).…”

Section: Study 5: Effects Of 7 Day Repeated Ipvn Administration Of Rementioning

confidence: 99%

“…The filter was exposed to phosphoscreen overnight prior to quantification of UCP-1 mRNA expression using ImageQuant software (GE Healthcare, Chalfont St Giles, UK). Blots were reprobed with oligo(dT) [12][13][14][15][16][17][18] to enable differences in RNA loading to be corrected.…”

Section: Study 5: Effects Of 7 Day Repeated Ipvn Administration Of Rementioning

confidence: 99%

Effects of acute and chronic relaxin-3 on food intake and energy expenditure in rats

McGowan

Stanley

Smith

et al. 2006

Regulatory Peptides

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119

158

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The effects of acute and repeated intraparaventricular (iPVN) administration of human relaxin-3 (H3) were examined on food intake, energy expenditure, and the hypothalamic-pituitary thyroid axis in male Wistar rats. An acute high dose iPVN injection of H3 significantly increased food intake 1 hour post-administration [0.4 ± 0.1g (vehicle) vs 1.6 ± 0.5g (180pmol H3), 2.4 ± 0.5g (540pmol H3) and 2.2 ± 0.5g (1620pmol H3), p< 0.05 for all doses vs vehicle]. Repeated iPVN H3 injection (180pmol/twice a day for 7 days) significantly increased cumulative food intake in ad libitum fed animals compared with vehicle [211.8 ± 7.1g (vehicle) vs 261.6 ± 6.7g (ad libitum fed H3), p< 0.05]. Plasma leptin was increased in the H3 ad libitum fed group. Plasma thyroid stimulating hormone was significantly decreased after acute and repeated administration of H3. These data suggest H3 may play a role in longterm control of food intake.

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Agouti-related protein has an inhibitory paracrine role in the rat adrenal gland

Cited by 45 publications

References 29 publications

Lys-gamma3-MSH: A global regulator of hormone sensitive lipase activity?

Lys-gamma3-MSH: A global regulator of hormone sensitive lipase activity?

Melanocortin-3 receptor regulates the normal fasting response

Effects of acute and chronic relaxin-3 on food intake and energy expenditure in rats

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