I t had been shown( 1) that porphyrins injected into ovariectomized mice produced a series of estrous reactions, which reoccurred after the porphyrin injections were discontinued. It had also been shown that injection of porphyrins into amphibians caused a release of the melanophore-expanding hormone from the intermediate lobe of the hypophysis( 2). It was, therefore, concluded that porphyrins had a stimulatory effect on the hypophysis and that the reactions following porphyrin injections were related to the secondary stimulation of the adrenal cortex. gonads, or melanophore system(3). When one of us attempted to induce estrous reactions by injecting porphyrin into ovariectomized mice, vaginal smears indicative of pseudo-estrous were obtained, but the results were not considered conclusive, Other methods to test the possible stimulatory influence of porphyrins on the hypophysis were then devised. In order to study any potential hypophyseal stimulator. the degree of specificity of response of the hypophysis should be evaluated. At the time that ACTH and Cortisone became popular therapeutic agents, it seemed desirable to devise a method of stimulating the hypophysis to produce greater amounts of ACTH, and it was hoped that hematoporphyrin would give rise to such specific stimulation.The hypothesis involved in these experiments was also based on the observations of Nelson (4), who demonstrated that Cortisone had a definite inhibitory effect on anaphylaxis in the mouse. Since ACTH stimulates the adrenal cortex to elaborate Cortisone and Cortisone-like compounds: it was postulated that if porphyrin stimulated hypophyseal ACTH output, it might thus have an indirect Cortisone-like influence on anaphylaxis in the mouse. These experiments, therefore, in-
t Mice in this experiment were the Strong A Strain or LCS, Strain (derived from crossing a CBAN with Strong A ) . Mice of these strains have been inbred for 90 and 26 generations respectively, and are thus quite uniform.
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