Lecture on blood pressure in pregnancy No. 10. The fetal-maternal barrier on bioactive peptide hormones. No.2

“The aminopeptidases which degrade hormones produced from fetus”

In normal pregnancy the fetus produces angiotensin, vasopressin and oxytocin with advancing gestation.

Although the production of vasopressin is much higher than that of oxytocin in the fetus, the ratio of vasopressin: oxytocin changes with advancing gestation. The equal ratio of vasopressin: oxytocin is achieved at later birth.

As I have shown previously, fetus increases markedly the production of both angiotensin and vasopressin at hypoxic state.

Both vasopressin and oxytocin are degraded by oxytocinase (P-LAP). We have shown the amino acid sequence of P-LAP in 1996(Ref1).The structure of oxytocin is similar to vasopressin.

The only one amino acid is different between them.

As I have shown that the blood pressure was observed in pregnant imprisoned women by administration of angiotensin.

Although there are many biological substances such as adrenaline which increase blood pressure in human, among them the most active biological substance in human body is angiotensin. In the previous blog I have introduced that angiotensinase (angiotensin degrading enzyme) research started around 1940 by gynecologists in USA. In 1981 we have shown that this enzyme has the degrading biological activity of angiotensin(blood pressure increasing activity) by cleavage of N-terminal amino acid Asp from angiotensin(,A-) and the existence of this enzyme in human placenta(Ref.2).

This enzyme is aminopeptidase A (APA). However this historical evidencethe essential role of hypertensive activity of A- is degraded by leakage of N-terminal amino acid Asp of A-, is still in dispute due to the recent armchair theory due to the new biological activity of angiotensin 1-7. We have shown that the knockout mouse of APA is hypertensive (Ref.3). We have shown that both APA and P-LAP might be the ideal drugs for both preeclampsia and preterm labor(Ref.4 ). Recently Brown CM and Garovic VD have suggested that both APA and P-LAP are novel therapeutic drugs for preeclampsia(Ref.5,6).


1. Rogi T, et al. Human placental leucine aminopeptidase/oxytocinase: a new member of type I membrane-spanning zinc

metallopeptidase family. J Biol Chem1996271:56-61

2. Mizutani s. et al.Aminopeptidase A in human placenta. Biochim Biophys Acta. 1981;678:168-170

3. Mitsui T et al. Hypertension and angiotensin hypersensitivity in aminopeptidase A deficient mice. Mol Med 2003;9:57-62

4. 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 Nov;22(11):1425-36. doi: 10.1517/13543784.2013.825248. Epub 2013 Aug 10. PMID:23931642

5. Brown CM, Garovic VD. Mechanisms and management of hypertension in pregnant women. Curr Hypertens Rep. (2011)13:338-346. doi:10.1007/s 11906-011-0214-y

6.Brown CM,Garovic VD.Drug Treatment of Hypertension in Pregnancy.Drugs. 2014 Mar;74(3):283-96. doi: 10.1007/s40265-014-0187-7.PMID:24554373











Dr.水谷のお産講座 No.39. 赤ちゃんが溺れてしまう水中分娩は絶対に止めましょう。愚の骨頂です。


















Lecture on blood pressure in pregnancy No.9: The fetal-maternal barrier on fetal bioactive peptide hormones. No. 1.


"The aminopeptidases which degrade hormones produced from fetus".


In this blog I will show you the placental aminopeptidases in both placenta and maternal blood which act as a barrier between fetus and mother with bioactive hormones produced from fetus.

Looking back the history of hormonal research, it is reminded that the research of the controlling factor of peptide hormones namely degrading substances has started much earlier than the hormone receptors. In addition this factor was studied in the obstetrics. The biological activity with vasoactive peptide hormones such as vasopressin and angiotensin and utero-tonic hormone, oxytocin were founded firstly in the extracted substances from animal brain. From the nineteen thirties they were synthesized chemically.   

Do you know about amino acids?  The protein is composed of amino acids. The peptide is named for the substances coupled with around 10 amino acids. The bioactive peptide hormones are consisted of less than 10 amino acids. While the administration of the extracted substances from animal brain have the biological activity in the animal, it has no biological activity in pregnancy animal. These observation have shown the existence of degrading activity of bioactive peptide hormones in pregnancy blood. The research with oxytocin and vasopressin degrading enzyme and angiotensin degrading enzyme started since  around 1940 by gynecologists in USA. The angiotensinase research was originated in the following experiment: the blood pressure was observed in pregnant imprisoned women by administration of angiotensin. While change of blood pressure was not observed in pregnant women at term, the marked rise of blood pressure by administration of angiotensin in puerperal women at 7 days after delivery. The magnitude of the rise in puerperal women by administration of angiotensin was decreased toward approaching delivery day. This observation show the existence of angiotensinase in pregnant women and the mechanisms of refractoriness against angiotensin in pregnant women which is well known and believed to be the probable cause of preeclampsia. While normal pregnant women have the refractoriness against angiotensin, preeclampsia patients lost this unique phenomenon and show the similar rise of blood pressure to normal men and non-pregnant women by administration of angiotensin.

From nineteen thirties synthetic oxytocin was started to be used as a labor pain inducing agent in USA and in Japan after the Pacific War. I will ask  you one question. I have shown the existence of oxytocinase in pregnant women suggesting disappearance of oxytocin activity by administration of this substance. Why does oxytocin act as a labor pain inducing agent?  To tell the truth utero-tonic activity of oxytocin is dramatically changed at the stage of pregnancy. Since it works dramatically, it results in uterine rupture according to the stage of pregnancy and also to its doses. On the other hand placental leucine aminopeptidase (P-LAP) namely oxytocin and vasopressin degrading enzyme produced from placenta increases with advancing pregnancy in the blood. However P-LAP stops its increase before 10 days before the onset of labor. Therefore at this stage oxytocin is very effective for inducing the labor pain. You might be able to get the image of the mechanisms of the onset of labor and also preeclampsia by this blog. Thank you












タイトル:Dr.水谷のお産講座 No.38.「乳児のうつ伏せ寝とカンガルーケアに共通する危険性」















 国民生活センターの危害情報システムには、抱っこベルト、 抱っこひも (子守帯)使用時の赤ちゃんの危害・危険情報が寄せられており、過去10年間で64件に達しています。




 “ねんねん子守よ”という古くからの歌がありますが、赤ちゃんは背中におんぶするのが安全な子守法なのです。新生児保育の基本は、赤ちゃんが楽に呼吸できる仰向け寝が基本です。 子供をがけから突き落として、這い上がってくる子供だけを育てるライオンと人は違います。








Dr.水谷のお産講座 No.37.「妊婦さんの飲酒は胎児に悪影響を及ぼします」











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