Inactivation of the Adipokinetic Property of Adrenocorticotropin, β-Melanocyte-Stimulating Hormone, Vasopressin and Pituitary Fraction H by Tissues of the Rat and Rabbit
This report presents data on the rates of inactivation of 4 adipokinetic hypophysial peptides by adipose and extraadipose tissues of the rat and rabbit, and correlates these data with the in vitro and in vivo adipokinetic potencies of the peptides in these 2 species. The peptides under study (adrenocorticotropin, β-melanocyte-stimulating hormone, vasopressin and pituitary fraction H) were incubated for 1 hr with various tissue homogenates, and the adipokinetic activity remaining in the incubation mixture was then determined by introducing slices of rabbit, guinea pig, hamster or rat adipose tissue. The data showed: 1) Eight tissues of the rat (kidney, liver, adrenal, adipose tissue, lung, heart, testis and spleen) inactivate one or more of the peptides. 2) Ratios of the rates of inactivation of the 4 peptides vary markedly from one organ to another, and indicate the presence of at least 3 different inactivating enzymes in the rat. 3) While rat adipose tissue inactivates all 4 peptides under study, rabbit adipose tissue lacks inactivating capacity. This finding appears to explain why rabbit adipose tissue is more responsive than rat adipose tissue to stimulation by these peptides in vitro. 4) In the rat, kidney, adipose tissue and testis inactivate fraction H. In the rabbit, 6 or more tissues inactivate adrenocorticotropin, β-melanocyte-stimulating hormone and vasopressin, but none of these tissues inactivates fraction H. These findings appear to explain the longer duration (4–10 hr) of the FFA mobilization which is produced in the intact rabbit by fraction H, and which leads to hyperlipemia, compared to the briefer duration (1–4 hr) of that produced by adrenocorticotropin and vasopressin, which does not cause hyperlipemia. 5) The soluble fractions of adipose tissue, kidney, liver and adrenal from the rabbit have the same inactivating capacity for adrenocorticotropin as the soluble fractions of the same organs from the rat. The insoluble fractions of these 4 rabbit organs possess only ⅓ to 1/10 as much inactivating capacity as the insoluble fractions of the corresponding rat organs. The data indicate that in vitro adipokinetic potency of hypophysial peptides is decreased by the action of inactivating enzymes present in adipose tissue. In intact animals, the adipokinetic potency is also lowered by inactivating enzymes present in extra-adipose tissues. The enzyme systems in the rat which inactivate the adipokinetic property of hypophysial peptides differ from those found in the rabbit in substrate specificity, tissue distribution and cytologic location. (Endocrinology75: 867, 1964)