Study on the Inactivation of the Melanocyte Stimulating Hormone in the Body, Especially on the Role of the Liver and the Kidney

Abstract

When melanocyte stimulating hormone (MSH) is injected into an animal, the blood level of MSH decreases rapidly thereafter (Landgrebe, Reid and Waring, 1943). As only a small portion of injected MSH is excreted in the urine (Lerner, Shizume and Bunding 1954), the hormone is either rapidly inactivated or bound by tissue in the body.As the inactivation of posterior pituitary hormones by liver and kidney, and gonadotrophic hormones by liver has been reported previously, the role of liver and kidney in the rapid disappearance of MSH from the circulation has been studied.MSH was administered intravenously to hepatectomized dogs, dogs with injured liver and nephrectomized dogs, and the disappearance rate of injected MSH from the circulation was compared with that in normal dogs. In addition, the level of MSH in the portal vein and in the hepatic vein was compared after intravenous injection of MSH into normal dogs. In the second part of the study, inactivation of MSH was tested after incubation with homogenates of liver, kidney and other tissues.From these experiments, the following results were obtained. (1) When hog or dog MSH was injected into dogs, the blood level of injected MSH decreased rapidly thereafter. When hog or dog MSH was injected into hepatectomized dogs, the rate of disappearance was definitely retarded as compared with that in normal dogs.(2) Similar retardation, although in lesser degree, of the disappearance of injected MSH from the circulation, was observed in the dogs whose livers were injured with carbon tetrachloride.(3) When MSH was injected into normal dogs, the level of MSH in the hepatic vein was always lower than that in the portal vein, and MSH was not found in the bile.(4) When hog MSH was injected into nephrectomized dogs, the rate of disappearance was retarded as compared with that in normal dogs, although in lesser degree compared with that in hepatectomized dogs.(5) When MSH was incubated with homogenates of various tissues of the dog at 37°C., homogenate of liver, kidney and muscle inactivated MSH. The degree of inactivation was most marked by the liver, next by the kidney and then by the muscle. When these homogenates were boiled before incubation or incubation was performed at 4°C., no inactivation was observed.These results indicate that liver and kidney play great roles in the inactivation of MSH and this inactivation is performed by some enzymatic system.