2013年02月

Placental Leucine Aminopeptidase (P-LAP)“胎盤性ロイシンアミノペプチダーゼ ”とは?

P-LAP:オキシトシンはヒトの脳下垂体(胎児と母体)から分泌されます。オキシトシンは妊娠末期の子宮を強力に収縮させるので、陣痛誘発剤として広く使用されます。しかしながら、妊娠中期の子宮は、オキシトシンによって殆ど収縮しません:妊娠中期の子宮はオキシトシンに抵抗性があります。一方、オキシトシンは胎児・胎盤系では、その発育因子の一つとして働いているようです。すなわちオキシトシンの作用は、母体側と胎児側では、全く異なっているようです。P-LAP はヒト胎盤で作られ、胎盤と母体血液ではオキシトシンの分解酵素として働いています(オキシトシナーゼ)。我々は1970年頃から、オキシトシナーゼをP-LAPと命名して、胎盤機能検査として、臨床応用してきました。P-LAPは非妊娠血液には存在しません。妊娠時には、妊娠の進行とともに増加をし、妊娠末期には約100単位に増加します。P-LAPの測定は簡単で、迅速に行えますので、胎盤機能の評価には信頼のおける検査の一つです。私が、日本産科婦人科学会理事として働いていました時には、P-LAPの検査は健康保険適用の胎盤機能検査として認められていましたが、私が名古屋大学退官後しばらくすると、P-LAPの検査は健康保険適用から除外され、しかも若い産婦人科医の教育プログラムの中の指針からも除外されてしまいました。

 

しかしながら、どっこい私のネーミングのP-LAPは生きていて、本年9月に、イタリアでinsulin-regulated aminopeptidase (IRAP)/oxytocinase/placental leucine aminopeptidaseの研究会がPhilip Thompson and Siew-Yeen Chai (Monash University) Anders Hallberg (Uppsala University)らが主催して開催されます:Italian city of Prato from September 9-11, 2013。ですから、私が1970年頃から始めたP-LAPの研究は今や世界で広くおこなわれているのです。残念ながら、産婦人科領域ではなく、免疫学、糖尿病研究や脳・神経(記憶 )分野など幅広い分野でP-LAP研究は発展しています。

What is P-LAP(placental leucine aminopeptidase)※?

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.

 

 

 

 

 

 

 

ホルモン療法との出会い(No.4):治療の実際

妊婦は当時29歳。前回妊娠時にも重症妊娠中毒症を発症していました。

・・・続きは会員限定です。
また、理事長の著書「
妊娠中毒症と早産の最新ホルモン治療」には、今回の記事の内容が詳しく書いてあります。ぜひ一度ご覧下さい。
アマゾンからお買い求めいただけます

続きを読む

Encounter with sex steroid hormone therapy (No 4):

Encounter with sex steroid hormone therapy (No 4):  first case of sex steroid therapy in severe preeclampsia in Japan

( the first case with estrogen-progesterone therapy; in 1969)

A 32-year old women  (gravida-3, para-1) had a history of severe preeclampsia during
previous conception.  At week 30 she was hospitalized to my father’s hospital
because of prominent edema and possible fetal growth retardation.



Although she was treated with bed rest, and furosemide was administered, her blood
pressure abruptly rose up to 190/130 mmHg and proteinuria developed. Seven days
after admission (observation time), administration of estradiol and progesterone was
started and maintained for 23 days. On the 4th day of steroid treatment serum
P-LAP
levels fell to a very low level of 25 mg/dl/h (unit). 



Thereafter it was increased to nearly the mean value of a normal pregnancy
( week 33), while the blood pressure gradually decreased and the body weight
was lowered.  When the P-LAP level showed its peak at week 33, her blood
pressure fell to 148/110 mmHg. Despite continuation of this treatment,
the P-LAP level thereafter started to show a decreasing tendency again, and

improvement of hypertension could not observe any longer.



 Cesarean section was performed because of the decreasing tend of P-LAP
more than 9 days, a male infant weighing 1,750 g( Apgar score 8) was
delivered uneventfully at week 35.



Please see our NPO home page: natural hormonal therapy for pregnancy
induced (gestational) hypertension and preterm birth, c) severe clinical
cases Case 7.

P-LAP:I will mention about P-LAP in next time.

 


 


 


 

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