论文标题

孕酮:矿物皮质受体的神秘配体

Progesterone: An Enigmatic Ligand for the Mineralocorticoid Receptor

论文作者

Baker, Michael E., Katsu, Yoshinao

论文摘要

孕激素受体(PR)介导了女性和男性中脑,骨骼,肺部和脉管系统等非成熟组织中女性生殖生理学的孕激素调节以及基因转录。孕酮的异常特性是其对矿物皮质激素受体(MR)的高亲和力,该受体调节人类和其他陆脊椎动物的肾脏中的电解质转运。在人类,大鼠,鳄鱼和青蛙中,孕激素拮抗了甲状腺生理矿物皮质激素醛固酮的MR激活。相比之下,在大象鲨鱼,射线污染的鱼类和鸡中,孕酮激活了MR。有趣的是,软骨鱼和射线灌溉的鱼不会合成醛固酮,这提出了一个类固醇激活软骨鱼和射线丝鱼中MR的问题。与皮质醇和其他皮质固醇相比,孕酮的简单合成使孕酮成为大象鲨鱼和射线污染鱼类中MR的候选生理激活剂。大象鲨鱼和射线污染的鱼MRS在包括心脏,脑和肺在内的多种组织中表达,以及卵巢和睾丸,这是孕酮的两个生殖组织,共同提出了MR在Elephant Shark和Rayfinned Fish中的孕激活的多方面生理作用。孕酮是某些陆地脊椎动物MRS和作为鱼类和鸡肉MRS的激动剂的拮抗剂的功能后果。实际上,通过任何脊椎动物MR的孕酮生理活性知之甚少。

The progesterone receptor (PR) mediates progesterone regulation of female reproductive physiology, as well as gene transcription in non-reproductive tissues, such as brain, bone, lung and vasculature, in both women and men. An unusual property of progesterone is its high affinity for the mineralocorticoid receptor (MR), which regulates electrolyte transport in the kidney in humans and other terrestrial vertebrates. In humans, rats, alligators and frogs, progesterone antagonizes activation of the MR by aldosterone, the physiological mineralocorticoid in terrestrial vertebrates. In contrast, in elephant shark, ray-finned fishes and chickens, progesterone activates the MR. Interestingly, cartilaginous fishes and ray-finned fishes do not synthesize aldosterone, raising the question of which steroid(s) activate the MR in cartilaginous fishes and ray-finned fishes. The simpler synthesis of progesterone, compared to cortisol and other corticosteroids, makes progesterone a candidate physiological activator of the MR in elephant sharks and ray-finned fishes. Elephant shark and ray-finned fish MRs are expressed in diverse tissues, including heart, brain and lung, as well as, ovary and testis, two reproductive tissues that are targets for progesterone, which together suggests a multi-faceted physiological role for progesterone activation of the MR in elephant shark and ray-finned fish. The functional consequences of progesterone as an antagonist of some terrestrial vertebrate MRs and as an agonist of fish and chicken MRs are not fully understood. Indeed, little is known of physiological activities of progesterone via any vertebrate MR.

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