What is P-LAP(placental leucine aminopeptidase)?


-LAP:oxytocin is secreted from human hypothalamus(fetal and mother).

Since oxytocin contracts actively the pregnant uterus just before onset of labor,
it is commonly used as agent of initiation of human labor. However, pregnant uterus
at mid pregnancy is resistant to oxytocin administration: oxytocin does not initiate
pregnant uterine contraction at mid pregnancy.


On the other hand, oxytocin in fetoplacental unit might work as one of the growth
activating factors. In fetal side, the role of oxytocin in pregnancy might be
completely different from that in maternal side.


P-LAP is produced from human placenta and works as a barrier for protecting
the leakage of fetal oxytocin into maternal blood (oxytocin degrading enzyme

: oxytocinase). We have named this enzyme for P-LAP. We used it clinically for
estimating placental function from around 1970.


P-LAP is not present in non-pregnant blood. During pregnancy, P-LAP in pregnancy
blood increases with advancing gestation and reach around 100 unit at term.
The measurement of P-LAP is simple and quick. It is a reliable test for judging
well-being of fetus.


When I was working as a member of board member of Japan Society of Obstetrics
and Gynecology, P-LAP test was acknowledged and approved for one of the Japan
Health Insurance and available placental function tests in pregnant women.


After my retirement from my university, this test was omitted from Japan Health
Insurance and also omitted from the educational protocol for young obstetricians
in Japan.


In 1996 we have cloned cDNA of P-LAP from human placenta. Unexpectedly P-LAP
was also cloned in USA from mouse almost the same time. The work was derived from
 the research with diabetes mellitus

The action of insulin is to reduce the blood glucose level via taking glucose into mainly
fat cells. This action is due to glucose transporter which is usually located in fat and
muscle cells. When insulin is secreted into blood, insulin translocates the glucose
transporter to cell membranes via insulin receptor on cell membrane. The glucose
transporter then transport into various cells.

In USA from 1990 some drug companies and universities were studying big molecule
protein which is co-localized in the glucose transporter. The cloning of oxytocinase
and big molecule protein which is co-localized in the glucose transporter was almost
the same.

Our cloned P-LAP was the rat homologue of P-LAP. In 1997 I have negotiated with
the researcher in USA who was responsible for the cloning for intending the unification
of the name. Regrettably many researchers preferred the name derived from the
researchers in diabetes mellitus. At present insulin-regulated aminopeptidase is
a common name instead of P-LAP. However I am happy to know that Meeting entitled”
insulin-regulated aminopeptidase/oxytocinase/ placental leucine aminopeptidase
“which is organized by Dr. Philip Thompson and Siew-Yeen Chai (Monash University)
and Dr.Anders Hallberg (Uppsala University) will be held in Italian city of Prato from
September 9-11, 2013.

Many researchers in the world is now working on P-LAP, which I have started its
research from around 1970. Regrettably OB/GY doctors have forgotten this important
research field, with which it might be able to understand the mechanisms of preeclampsia
and preterm labor, in addition to the mechanisms of onset of labor. At present many
researchers in immunology, diabetes mellitus, brain and nerve functions (memory) and
other various fields are actively working on related to P-LAP problems.