Division of Nephrology-Hypertension, Department of Medicine, 0735, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0735, United States.
Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
Biochem Pharmacol. 2020 Jul;177:113976. doi: 10.1016/j.bcp.2020.113976. Epub 2020 Apr 17.
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. The physiological activities of progesterone through binding to vertebrate MRs merits further investigation.
孕激素受体（PR）介导孕激素对女性生殖生理的调节，以及在非生殖组织（如脑、骨、肺和脉管系统）中的基因转录，这在男性和女性中都是如此。孕激素的一个不寻常特性是其与盐皮质激素受体（MR）的高亲和力，后者在人类和其他陆生脊椎动物中调节肾脏中的电解质转运。在人类、大鼠、短吻鳄和青蛙中，孕激素拮抗醛固酮（陆生脊椎动物的生理性盐皮质激素）对 MR 的激活。相比之下，在软骨鱼和硬骨鱼中，孕激素激活 MR。有趣的是，软骨鱼和硬骨鱼不合成醛固酮，这就提出了一个问题，即哪种类固醇（s）在软骨鱼和硬骨鱼中激活 MR。与皮质醇和其他皮质类固醇相比，孕激素的合成更为简单，这使得孕激素成为软骨鱼和硬骨鱼中 MR 的生理性激活剂的候选物质。软骨鱼和硬骨鱼的 MR 在多种组织中表达，包括心脏、大脑和肺，以及卵巢和睾丸，这两个生殖组织是孕激素的靶标，这表明孕激素激活 MR 在软骨鱼和硬骨鱼中具有多方面的生理作用。孕激素作为一些陆生脊椎动物 MR 的拮抗剂和鱼类和鸡 MR 的激动剂的功能后果尚未完全了解。通过与脊椎动物 MR 结合，孕激素的生理活性值得进一步研究。
