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首页> 外文期刊>American Journal of Physiology >Effect of a melanocortin type 2 receptor (MC2R) antagonist on the corticosterone response to hypoxia and ACTH stimulation in the neonatal rat
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Effect of a melanocortin type 2 receptor (MC2R) antagonist on the corticosterone response to hypoxia and ACTH stimulation in the neonatal rat

机译：黑素旋蛋白2型受体（MC2R）拮抗剂对新生大鼠缺氧和Acth刺激的皮质酮反应的影响

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The adrenal stress response in the neonatal rat shifts from ACTH-independent to ACTH-dependent between postnatal days 2 (PD2) and 8 (PD8). This may be due to an increase in an endogenous, bioactive, nonimmunoreactive ligand to the melanocortin type 2 receptor (MC2R). GPS 1574 is a newly described MC2R antagonist that we have shown to be effective in vitro. Further experimentation with GPS 1574 would allow better insight into this seemingly ACTH-independent steroidogenic response in neonates. We evaluated the acute corticosterone response to hypoxia or ACTH injection following pretreatment with GPS 1574 (32 mg/kg) or vehicle for GPS1574 in PD2, PD8, and PD15 rat pups. Pretreatment with GPS1574 decreased baseline corticosterone in PD2 pups but increased baseline corticosterone in PD8 and PD15 pups. GPS 1574 did not attenuate the corticosterone response to hypoxia in PD2 pups and augmented the corticosterone response in PD8 and PD15 pups. GPS1574 augmented the corticosterone response to ACTH in PD2 and PD15 pups but had no significant impact on the response in PD8 pups. Baseline adrenal Mrap and Star mRNA increased from PD2 to PD15, whereas Mrap2 mRNA expression was low and did not change with age. The data suggest that GPS 1574 is not a pure MC2R antagonist, but rather acts as a biasing agonist/ antagonist. Its ability to attenuate or augment the adrenal response may depend on the ambient plasma ACTH concentration and/or developmental changes in early transduction steroidogenic pathway genes.
机译：新生大鼠的肾上腺胁迫反应从后期2（PD2）和8（PD8）之间的acth-无关依赖于依赖于Acth依赖性。这可能是由于内源性，生物活性，非免疫激素配体的增加，对黑色素蛋白2型受体（MC2R）。 GPS 1574是一种新描述的MC2R拮抗剂，我们已显示在体​​外有效。与GPS 1574的进一步实验将更好地深入了解新生儿的这种看似独立的独立类分子化的类化反应。在PD2，PD8和PD15大鼠幼崽中对GPS 1574（32mg / kg）或载体进行预处理，评估对缺氧或acth注射的急性皮质酮反应。用GPS1574预处理降低PD2幼崽的基线皮质酮，但PD8和PD15幼崽中的基线皮质酮增加。 GPS 1574没有衰减PD2幼崽中缺氧的皮质酮反应，并在PD8和PD15幼崽中增强皮质酮反应。 GPS1574增强了PD2和PD15 PUP中的acticOsterone对acth的响应，但对PD8幼崽的反应没有显着影响。基线肾上腺MRAP和星形mRNA从PD2增加到PD15，而MRAP2 mRNA表达低，并且随着年龄的增长而没有改变。数据表明，GPS 1574不是纯MC2R拮抗剂，而是用作偏置激动剂/拮抗剂。其衰减或增强肾上腺反应的能力可能取决于早期转导针分途径基因的环境血浆诱发和/或发育变化。

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