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

Agouti-related protein has an inhibitory paracrine role in the rat adrenal gland
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DOI:
10.1016/s0006-291x(02)02991-1
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发表时间:
2003-01-31
影响因子:
3.1
通讯作者:
Bloom, SR
Bloom, SR
中科院分区:
生物学4区
文献类型:
--
作者:
Dhillo, WS;Small, CJ;Bloom, SR

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α-促黑素细胞激素(α-MSH)是黑皮质素3受体(MC 3-R)和黑皮质素4受体(MC 4-R)的激动剂。α-MSH刺激体外大鼠肾上腺肾小球细胞释放皮质酮Agouti-related protein(AgRP)是一种内源性MC 3-R和MC 4-R拮抗剂,在肾上腺中表达。我们研究了MC 3-R和MC 4-R在肾上腺中的表达以及AgRP的作用。用RT-PCR方法检测大鼠肾上腺MC 3-R和MC 4-R的表达。使用分散的大鼠肾上腺肾小球细胞研究AgRP对α-MSH诱导的皮质酮释放的影响。AgRP单独给药不影响皮质酮释放,但AgRP和α-MSH共同给药减弱α-MSH诱导的皮质酮释放。为了研究糖皮质激素反馈,比较了用地塞米松处理的大鼠与对照组的肾上腺AgRP表达。与对照组相比,用地塞米松处理的大鼠中AgRP mRNA增加。我们的研究结果表明肾上腺AgRP mRNA受糖皮质激素的调节。通过MC 3-R或MC 4-R起作用的AgRP可能具有抑制性旁分泌作用,阻断α-MSH诱导的皮质酮分泌。(C)2002 Elsevier Science(美国)。All rights reserved.
alpha-Melanocyte-stimulating-hormone (alpha-MSH) is an agonist at the melanocortin 3 receptor (MC3-R) and melanocortin 4 receptor (MC4-R). alpha-MSH stimulates corticosterone release from rat adrenal glomerulosa cells in vitro. Agouti-related protein (AgRP) an endogenous antagonist at the MC3-R and MC4-R, is expressed in the adrenal gland. We investigated the expression of the MC3-R and MC4-R and the role of AgRP in the adrenal gland. MC3-R and MC4-R expression was detected in rat adrenal gland using RTPCR. The effect of AgRP on alpha-MSH-induced corticosterone release was investigated using dispersed rat adrenal glomerulosa cells. AgRP administered alone did not affect corticosterone release, but co-administration of AgRP and alpha-MSH attenuated alpha-MSH-induced corticosterone release. To investigate glucocorticoid feedback, adrenal AgRP expression was compared in rats treated with dexamethasone to controls. AgRP mRNA was increased in rats treated with dexamethasone treatment compared to controls. Our findings demonstrate that adrenal AgRP mRNA is regulated by glucocorticoids. AgRP acting via the MC3-R or MC4-R may have an inhibitory paracrine role, blocking alpha-MSH-induced corticosterone secretion. (C) 2002 Elsevier Science (USA). All rights reserved.