Erythropoietin is a hormone produced in the kidney to stimulate the generation of more red blood cell. It is triggered by low oxygen via HIF transcription factors. Makes sense. Oops, oxygen is low, let's make more erythrocytes to carry more oxygen from the lung to consuming cells.

What doesn't make sense is why evolution would locate the production of EPO in the kidneys. These are organs tasked with excretion via the urine - pump and retrieve. They have very little to do with red blood cell gas exchange (lungs), generation (bone marrow), or removal (spleen).

Can somebody think of a good reason why you would locate the synthesis and release of the primary hormone to trigger red blood cell generation in a seemingly unrelated organ like the kidneys?

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    $\begingroup$ There's no reason that an endocrine tissue should be related to the target tissue of the hormone it produces. Think of other examples, e.g. liver glucagon, islets insulin, adrenals epinephrine. The only requirement is that it should be able to detect conditions in which it is appropriate to release the hormone. Your question would be better if you removed the false premise and just asked how the kidney detects a change in oxygen tension. $\endgroup$
    – David
    Commented Oct 31, 2018 at 13:58
  • $\begingroup$ Evolution adds randomness but function is still selected for. The hunger hormone ghrelin is produced in the stomach when it's not stretched by food and the satiety hormone leptin is produced in adipocytes when fat stores are filled. Insulin and glucagon both come from the pancreatic islets, strategically positioned in the blood stream right after nutrient uptake in the gut and before the liver, the main storage organ. The question remains is EPO the exception without a good reason? $\endgroup$
    – SeanJ
    Commented Nov 6, 2018 at 14:29
  • $\begingroup$ As I pointed out, it isn't an exeption any more than insulin, glucagon or epinephrine. However, if I were a developmental biologist I might think about the role or developmental stage of tissues in early foetal (and even embryonic) development to consider why the bone marrow might be inappropriate. I'm a more molecular biologist, so I can't, but I suspect the more physiological biologists should be able to discuss this. Seems there aren't any on this list that want to dip their toes in the water. ( Is your 'surprise' partly psychological because of the association of kidneys with urination?) $\endgroup$
    – David
    Commented Nov 6, 2018 at 16:18


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