The hypothalamic melanocortin system stimulates the hypothalamo-pituitary-adrenal axis in vitro and in vivo in male rats
The hypothalamic melanocortin system stimulates the hypothalamo-pituitary-adrenal axis in vitro and in vivo in male rats
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DOI：
10.1159/000054712
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发表时间：
2002-04-01
影响因子：
4.1
通讯作者：
Bloom, SR
中科院分区：
文献类型：
--
作者：
Dhillo, WS;Small, CJ;Bloom, SR
α-促黑素细胞激素（α-MSH）是中枢神经系统（CNS）中发现的黑皮质素3和4受体的激动剂，而刺豚鼠相关蛋白（Agrp）是内源性拮抗剂。我们在雄性大鼠体内和体外研究了α-MSH和Agrp对下丘脑-垂体-肾上腺（HPA）轴的影响。室旁核（iVN）内注射[Nle（4），D-Phe（7）]-α-MSH（NDP-MSH）（长效α-MSH类似物）增加血浆促肾上腺皮质激素（ACTH）（注射后10分钟：25.0 +/- 3.9 vs.盐水10.9 +/- 2.0，p < 0.05）和血浆皮质酮（注射后10分钟：174.1 +/-14.2 vs.盐水124.7 +/-16.3ng/ml，p < 0.05）。iPVN注射Agrp（83-132）增加血浆ACTH（24.2 +/-4.0对盐水10.1 +/-1.0 pg/ml，p < 0.01）。NDP-MSH和Agrp（83-132）的组合施用iPVN显著增加血浆ACTH（注射后10分钟：21.3 +/- 3.8 vs. 10.9 2.0，p < 0.05）和血浆皮质酮（注射后10分钟：169.0 +/-15.1 vs.盐水124.7 +/-16.3 ng/ml，p < 0.05），但无累加效应。与基础相比，用α-MSH（100 nM）处理的下丘脑外植体导致促肾上腺皮质激素释放激素（CRH）释放增加159 +/-23%（p < 0.01）和精氨酸加压素（AVP）释放增加175 +/-12%（p < 0.001）。与基础水平相比，对下丘脑外植体给予Agrp（83-132）（100 nM）导致CRH增加161 +/- 20%（p < 0.01），AVP释放增加174 +/- 13%（p < 0.001）。与基础相比，用α-MSH和Agrp（83-132）（100 nM）的组合处理的下丘脑外植体导致CRH释放增加179 +/-31%（p < 0.01）和AVP释放增加130 +/-9%（p < 0.01），但没有累加效应。这是首次报道α-MSH和Agrp（83-132）都刺激HPA轴。α-MSH和Agrp（83-132）的组合在雄性大鼠中在体外和体内没有累加效应。这些结果表明，可能有另一种受体独立于已知的黑皮质素受体Agrp的作用。
a-Melanocyte-stimulating hormone (alpha-MSH) is an agonist, and agouti-related protein (Agrp) an endogenous antagonist at the melanocortin 3 and 4 receptors which are found in the central nervous system (CNS). We have examined the effect of a-MSH and Agrp on the hypothalamo-pituitary-adrenal (HPA) axis in vitro and in vivo in male rats. Intraparaventricular nuclear (iPVN) injection of [Nle(4),D-Phe(7)]-alpha-MSH (NDP-MSH) (a long-acting alpha-MSH analogue) increased plasma adrenocorticotropic hormone (ACTH) (10 min post-injection: 25.0 +/- 3.9 vs. saline 10.9 +/- 2.0, p < 0.05) and plasma corticosterone (10 min post-injection: 174.1 +/- 14.2 vs. saline 124.7 +/- 16.3 ng/ml, p < 0.05). iPVN injection of Agrp(83-132) increased plasma ACTH (24.2 +/- 4.0 vs. saline 10.1 +/- 1.0 pg/ml, p < 0.01). The combination of NDP-MSH and Agrp(83-132) administered iPVN significantly increased plasma ACTH (10 min post-injection: 21.3 +/- 3.8 vs. 10.9 2.0, p < 0.05) and plasma corticosterone (10 min post-injection: 169.0 +/- 15.1 vs. saline 124.7 +/- 16.3 ng/ml, p < 0.05), but there was no additive effect. Hypothalamic explants treated with a-MSH (100 nM) resulted in a 159 +/- 23% increase in corticotropin-releasing hormone (CRH) release (p < 0.01) and 175 +/- 12% increase in arginine vasopressin (AVP) release (p < 0.001) compared to basal. Agrp(83-132) (100 nM) administered to hypothalamic explants resulted in a 161 +/- 20% increase in CRH (p < 0.01) and 174 +/- 13% increase in AVP release (p < 0.001) compared to basal. Hypothalamic explants treated with the combination of alpha-MSH and Agrp(83-132) (100 nM) resulted in a 179 +/- 31% increase in CRH release (p < 0.01) and 130 +/- 9% increase in AVP release (p < 0.01) compared to basal, but there was no additive effect. This is the first report that both alpha-MSH and Agrp(83-132) stimulate the HPA axis. The combination of alpha-MSH and Agrp(83-132) has no additive effect in vitro and in vivo in male rats. These results suggest that there may be another receptor independent of the known melanocortin receptors at which Agrp is acting.