Dear friends,


In August 2013, we published a review article on preeclampsia and preterm labor in the journal named Expert Opinion on Investigational Drugs.(1)  In the review,  we gave our  comprehensive picture of physiology of child birth and highlighted my view of etiology underlying preterm labor and preeclampsia . On set of these abnormality is gestational age-dependent imbalance between fetal oxytocin,vasopressin and angiotensin secretion and their inactivation by maternal (placental) leucine aminopeptidase or P-LAP and aminopeptidase A. It is the root cause for the failure in carrying fetus along pregnancy that eventually break into a threshold, the induction of labor earlier than the normal term and preeclampsia . Oxytocin binds to the oxytocin receptors of the uterus and stimulates contraction but this action is counterbalanced by oxytocin hydrolyzation by P-LAP under normal pregnancy. All causes of unbalanced concentration of these substances, oxytocin vasopressin and angiotensin derived from fetus and P-LAP and and aminopeptidase A produced from placenra, before term, such as seen in preeclampsia and preterm labor can put the pregnancy into the risk of preterm labor and preeclampsia. Premature birth can be a significant neonatal mortality and morbidity or after birth physical and mental health problems. Unfortunately, almost all medical attempts to reverse the condition, such as administrations of bolus magnesium sulfate or beta adrenergic  stimulants, are no safer than toxic chemicals that retard nervous development and many adverse effects of the fetus. Having endorsed by our previous experiments using P-LAP and aminopeptidase A knock out mice and clinical evidences of P-LAP and  aminopeptidase A dynamics that correlated with gestational age, the medical treatment with recombinant P-LAP and aminopeptidase A must be developed as soon as possible.

Encouraging enough, almost same time to my publication, a group of scientists from Iowa University dispatched the results of their impressive research on genetic sequence variants of preterm birth. (2)  In this study, the group attempted more than 2400 multinational case control analysis and identified three allelic mutations significantly associated to preterm birth and these were on the gene encoding P-LAP. This evidence explicitly indicates the central role of P-LAPin regulating gestation because the mutation in maternal genome of this enzyme specifically and significantly correlated to stratified preterm gestational age groups. It is well known that vasopressin, a stress hormone, is particularly important during septic shock in human because a relative deficiency of vasopressin is reported in this condition. Scientists from the University of British Columbia reported also that the genetic variation in vasopressinase (P-LAP) is associated with 28-day mortality in septic shock and is associated with biological effects on vasopressin clearance and serum sodium regulation. (3) Therefore

 the genetic variation in P-LAP is suggested to be linked to not only preterm labor, but also human shock.




(1)Mizutani S. et al., New insights into the role of aminopeptidases in the treatment for both preeclampsia and preterm labor. Expert Opin Investig Drugs 2013 Aug 10.

(2)Kim J. et al., Sequence variants in oxytocin pathway genes and preterm birth: a candidate gene association study. BMC Medical Genetics 2013, 14;77

(3) Nakada T et al., Leucyl/cystinyl aminopeptidase gene variation in septic shock. Chest 2010,DOI:10.1378/chest.10-2517