Inactivation of neurohypophyseal hormones colostrum and serum of human and other mammals

Abstract

Human colostrum, collected from the day prior to delivery to 3 days postpartum, inactivated oxytocin more slowly than arginine-vasopressin or lysinevasopressin. The presence of enzymes with the ability to attack chemical substrates by mechanisms proposed for the degradation of oxytocin was studied in these colostrum samples and in human serum. Placental cystine aminopeptidas (oxytocinase) activity was usually elevated only in peripheral serum, while levels of non-specific aminopeptidases, as measured using ▪-leucyl-β-naphthylamide as substrate, were high in human colostrum as well as serum. An enzyme possessing glutathione-protein disulfide oxidoreductase activity with cystine as a substrate is suggested to be present in the colostrum but not in postpartum serum. Colostrum and plasma of rhesus monkey also inactivated neurohypophyseal hormones as did the colostrum of cat. Although both human serum and colostrum were rich in heat-stable alkaline phosphatease activity, reflecting increased capillary permeability at term, the low levels of cystine aminopeptidase activity in colostrum suggest that the degradation of neurohypophyseal hormones by colostrum occurs predominantly or solely by enzymes present in the mammary gland, which are different from placental cystine aminopeptidase. Werle (1960) reported that “colostrum of woman and cow has very low activity in splitting oxytocin.” More recently, Walter (1973) showed oxytocin inactivation by human colostrum to be greatest during the first 24 hours postpartum and to diminish quickly in subsequent days. Since the C-terminal octapeptide of oxytocin was identified as the major degradation product and since [1,6-aminosuberic acid]oxytocin — an analog not susceptible to exopeptidase and disulfide oxidoreductases — was not inactivated, it was concluded that cleavage of the Cys-Tyr peptide bond is the initial step in the degradation of the hormone by human colostrum. This route of enzymatic oxytocin inactivation was first suggested to occur in serum of pregnant women (Tuppy and Nesvadba, 1957; Sjöholm and Yman, 1967) and has since been postulated for other tissues ( e.g. , Tuppy, 1968; Celis et al. , 1971 ; Kleiner and Brouet-Yager, 1973). The possibility of prior reductive cleavage of the disulfide bond of the hormone by enzymes present in human colostrum was not ruled out. In this work, enzymes in human colostrum capable of degrading oxytocin were further characterized and compared to enzymes of placental origin. The degradation of arginine- and lysine-vasopressin by human colostrum was also investigated. The capability of colostrum and plasma of rhesus monkey, and colostrum of cow, goat and cat to degrade oxytocin was tested.