Changes in Cystine Aminopeptidase (Oxytocinase) Activity in Mouse Serum, Placenta, Uterus and Liver during Pregnancy or after Steroid Hormone Treatments

Abstract

Changes in cystine aminopeptidase (CAP) activity in serum, placenta, uterus and liver in mice under various physiological conditions were examined by enzymatic analysis using S-benzyl-L-cysteine-4-methylcoumaryl-7-amide as a substrate. Changes in serum CAP activity during pregnancy were less remarkable than those reported in humans; the activity was highest at day 13 of pregnancy and lowest at day 17. During the estrous cycle, the serum CAP level was high at diestrus, as high as that at day 13 of pregnancy. The activity in the male serum was significantly low compared to that in the diestrous serum. Although the CAP level was especially high in the maternal placenta, levels were also high in the fetal placenta, uterus and liver as compared with the serum, suggesting CAP synthesis in these tissues. The CAP activity in the uterine tissue was lower in pregnant than normal cycling mice. Furthermore, the serum CAP activity was modulated by estrogen and progesterone both in females and males, and by androgen in males. The relevance of these findings to the physiological role of CAP was discussed.

Characterization of a recombinant soluble form of human placental leucine aminopeptidase/oxytocinase expressed in Chinese hamster ovary cells

“…Using highly purified recombinant protein, we have confirmed in this study that P‐LAP/oxytocinase degraded peptide hormones such as oxytocin and vasopressin which have uterine contractive and vasoconstrictive activities, indicating potential significance of the enzyme in the maintenance of normal pregnancy. Further work in our laboratory aims to elucidate the biological significance of the release of P‐LAP into maternal serum [28], as it has been reported that aminopeptidases belonging to the membrane‐bound M1 metallopeptidase family are often released into serum during pregnancy [29,30] and soluble P‐LAP was detected only in the serum of pregnant women [5].…”

Urinary sex steroid hormone and placental leucine aminopeptidase concentration differences between live births and stillbirth of Bornean orangutans (Pongo pygmaeus)

“…16 A few studies on non-human animals have shown that PLAP concentration was high during pregnancy in sheep 17 and mice. 18 In many species, estrone-3-glucuronide (E 1 G) and pregnanediol-3-glucuronide (PdG) are abundant metabolites of estrogen and progesterone excreted into urine, which accurately reflect changes in circulating hormones and the maintenance of pregnancy, respectively. [19][20][21] Therefore, it is important to measure the concentrations of these hormone metabolites in urine to assess the endocrinological changes during pregnancy.…”

“…A few studies on non‐human animals have shown that PLAP concentration was high during pregnancy in sheep and mice . In many species, estrone‐3‐glucuronide (E 1 G) and pregnanediol‐3‐glucuronide (PdG) are abundant metabolites of estrogen and progesterone excreted into urine, which accurately reflect changes in circulating hormones and the maintenance of pregnancy, respectively …”

Structure-Activity Study of LVV-Hemorphin-7: Angiotensin AT4 Receptor Ligand and Inhibitor of Insulin-Regulated Aminopeptidase

“…IRAP is a type II membranespanning protein such that when at the plasma membrane the catalytic site is extracellular (Keller et al, 1995). The enzyme was initially defined as specifically cleaving the N-terminal amino acid CysXaa-, in which the half-cystine residue is involved in a disulfide loop, notably in oxytocin or vasopressin, but in vitro has also been demonstrated to cleave a range of peptides not containing disulfide loops (Matsumoto and Mori, 1998;Matsumoto et al, 2000). Our preliminary studies indicate that AT 4 ligands are not cleaved by IRAP (R. A. Lew, T. Mustafa, S. Ye, S. G. McDowall, S. Y. Chai, and A. L. Albiston, manuscript submitted for publication).…”