The 4 ringed structure also helps improve lipophilicity of the molecule, which is especially important because steroids need to cross the membrane into the cytoplasm to bind to nuclear receptors. They also help stabilize the molecule into a planar structure to facilitate membrane penetration.

Other ligands of nuclear receptors are produced from Acetyl CoA, like cholecalciferol (vitamin D3) and retinoids. As with nuclear receptors, steroids have a long genetic history. It seems estrogen receptors were among the first steroid receptors to appear, and mutations brought about more diverse roles for steroids.

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