Prostaglandin Dehydrogenase Activity In Trophoblast Cells Of The Early Human Placenta
Prostaglandin Dehydrogenase Activity In Trophoblast Cells Of The Early Human Placenta inludes relationship of PGDH to serum progesterone.
Prostaglandin dehydrogenase is an enzyme required for the first step of prostaglandin metabolism.
In human uterine and intrauterine tissues, oxidation of the 15-hydroxyl group of prostaglandins is
catalysed almost entirely by a NAD-linked 15-hydroxyprostaglandin dehydrogenase (PGDH) (1).
PGDH activity was measured in homogenates of 25 human placentae between 7 and 10 weeks of
gestation. Between 7 and 8 weeks of gestation and 15 and 16 weeks, mean values for PGDH
increased 10 fold. The data indicate that the development of terminal villi and the migration of
trophoblast into the maternal spinal arteries is associated with a substantial increase in the placental
capacity for prostaglandin metabolism (1). There was a large variation in PGDH activity between
individual placentae of each of the early gestational stages (1).
Prostaglandin E2 is a better substrate for this enzyme than Prostaglandin E1. The first step in the
metabolism of Prostaglandin E2 involves oxidation of the 15-hydroxyl group to its inactive
metabolite 15 Ketoprostaglandin E2 (2). There is a wide variation in the PGDH content in
individual placentas (2).
In early human placentae 15-OH PGDH activity decreases between 5 and 9 weeks and then
gradually increases in week 9. The activity was significantly lower than at other times during
gestation. The progesterone content of the placenta changes in a similar way to PGDH activity and
is lowest in week 9. On regression analysis there is a fairly close positive correlation (r2 = 0.69)
between PGDH activity and the concentration of progesterone in the placenta during the period
studied (3). Prostaglandin dehydrogenase is under progesterone control in reproductive tissues.
That is, if progesterone is raised, PGDH will be raised and PGE2 will be lowered. After treatment
with anti-progesterone RU 486, in vivo levels of PGDH fall in uterine tissues and PGE2 will be
It is relevant to relate anti-progesterone treatment for induction of early termination of pregnancy
to nausea and vomiting of pregnancy. Epostane, the competitive inhibitor of the enzyme 3B-
Hydroxysteroid dehydrogenase, therefore a specific anti-progesterone, when given in a dose of
200mg orally every 6 hours for 7 days in 50 women in the 5th through the 8th week of pregnancy,
nausea occurred in 86% of women (5). Thirty-four early pregnant women (duration of
amenorrhoea for up to 49 days) admitted to hospital for termination of their pregnancy received
25mg RU 486 (anti-progesterone, a progesterone receptor antagonist) twice or four times daily for
4 days. Seven patients (20%) had increased nausea during RU 486 treatment (6). It is reasonable
to suggest that the cause of increased nausea in both instances is due to lowered progesterone
activity in decidual and chorionic villus tissues, with lower prostaglandin dehydrogenase and raised
PGE2 tissue and maternal serum levels.
1. KIERSE M J N C, ERWICH J J H M, KLOK G.
Increase in placental 15-hydroxyprostaglandin dehydrogenase in the first half of human pregnancy.
2. JARABAK J.
Early steps in protaglandin metabolism in the human placenta.
Am J. Obstet Gynecol. 1980;138:534-540.
3. FALKAY G, SAS M.
Correlation between the concentration of prostaglandin dehydrogenase and progesterone in the early human placenta.
J. Endocrinol. 1978;76:173-4.
4. CHENG L, KELLY R W, THONG K J, HUME R, BAIRD D T.
The effect of mifepristone (RU 486) on the immunohistochemical distribution of Prostaglandin E and its metabolite in decidual and chorionic tissue in early pregnancy.
J. Clin Endocrinol Metab. 1993;77(3):873-877.
5. CROOIJ M J, NOOYER C C, RAO B R, BERENDS G T, GOOREN L J, JANSSENS J.
Termination of early pregnancy by the 3 beta hydroxysteroid dehydrogenase inhibitor Epostane.
New England Journal of Medicine. 1988;319(13):813-817.
6. BYGDEMAN M, SWAHN M-L.
Progesterone receptor blockage.
Effect on uterine contractility and early pregnancy.
85% of pregnant women have two episodes of nausea per day.
Nausea & vomiting in pregnancy (NVP) is very common, on average it affects 70-80% of pregnant women to a greater or lesser extent.
30% of pregnant women in paid employment need time off work due to NVP.
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