Oxytocin is hydrolytically cleaved in the presence of plasma oxytocinase to give an acyclic peptide, tyrosyl-isoleucyl-glutaminyl-asparaginyl-S-(S-cysteine)-cysteinyl-prolyl-leucyl-glycinamide (1,2-acyclic oxytocin). The synthesis of this peptide is described. It is shown to be of very low potency in milk-ejection-like activity and uterotonic activity. It does not inhibit the expression of these activities by oxytocin, suggesting that it does not interfere with the hormone's binding to target tissues. The presence of 1,2-acyclic oxytocin slightly inhibits the rate of degradation of oxytocin by plasma from pregnant women, in contrast to the marked inhibition of the degradation of cystine di-β-naphthylamide. The Km for the degradation of oxytocin is 30 times smaller than that of the degradation of cystine di-β-naphthylamide, which is of the same order as the Ki for the inhibition of the degradation of cystine di-β-naphthylamide by 1,2-acyclic oxytocin. These results, together with information on the substrate specificity of plasma oxytocinase with respect to the N-terminal amino acid residue, suggest that there are molecular features of oxytocin other than its N-terminal residue that facilitate its interaction with plasma oxytocinase.

Glutathione-insulin trandhydrogenase (GIT) activity has been shown to be stimulated in culture of explants of pregnant mouse mammary gland by a mixture of insulin, cortisol, and prolactin. Since this hormone mixture stimulates lactogenesis in vitro it is possible that the increase in GIT activity is functionally related to one of the processes of milk secretion or ejection. Oxytocin is degraded by GIT and the interaction of this hormone with its mammary gland receptors may be influenced by the change in enzyme activity. The increase in GIT activity caused by insulin, cortisol, and prolactin in vitro can be prevented by the addition of progesterone or oxytocin to the culture medium.