Fundamental Stimulus for Erythropoiesis

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Abstract
True erythropoietic stimulation can be achieved experimentally by only 3 conditions: anoxic anoxia, anemic anoxia and excessive cobalt. Reports of stimulation by distinctly different means have failed to satisfy all the criteria of true stimulation. The mechanism or mechanisms of action of the fundamental stimulus for erythropoiesis are not known. Since more than one mechanism of stimulation may well exist, exptl. inhibition or removal of one may favor an alternate route of action and thus confuse interpretation. Of the explanations suggested for erythropoietic stimulation, that of direct anoxic stimulation of marrow has had most articulate adherents. However, when this concept, which was based on indirect evidence and fortified by constant repetition, has been tested more directly, it has received no support. An alternate explanation is that anoxia, in one form or another, acts on the organism to produce a stimulating impulse which is eventually transmitted to the erythroid bone marrow. The participation of the nervous system as a means of transmission has not been demonstrated. The part played by the endocrine glands and the known hormones is one of modification of existing processes rather than initiation or absolute regulation. Of these glands, the pituitary appears to be the most significant. However, the hypophysectomized rat is capable of regenerating lost red blood cells and, given a sufficient anoxic stimulus, becomes polycythemic. The theories of self-regulatory mechanism proposed by Miyagawa and Verzar suggest that the products of erythrocyte destruction (hemoglobin, red cell stroma or bilirubin) stimulate the production of new red blood cells. These theories are similar and possess many attractive features, but further evidence is required. The hemopoietine concept of Paul Carnot proposes that in either anemic or anoxic anoxia, a blood-borne substance stimulates the erythroid bone marrow. Neither the site of formation nor the nature of this substance is known. Unequivocal confirmation of the presence and mode of action of hemopoietine undoubtedly awaits concn. or isolation of this substance from an erythropoietically stimulated organism. Despite the incomplete nature of the evidence, humoral mediation by hemopoietine or a similar agent seems to offer the most useful working hypothesis for investigations of the mechanism of action of the fundamental erythropoietic stimulus. 639 references.
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