Biosynthesis and catabolism of prostaglandin F2alpha (PGF2alpha) are controlled by progesterone in the rat uterus during pregnancy.
Myometrial quiescence is a key factor in all species to accomplish a successful gestation. PGs play a crucial role in mediating parturition events, and their synthesis and metabolism are regulated by cyclooxygenases (COXs) and NAD(+)-dependent 15-hydroxy-PG dehydrogenase (PGDH), respectively. Progesterone (P(4)) is the hormone responsible for maintaining uterine smooth muscle quiescence during pregnancy. In this work, we have studied the effect of P(4) on the activity of COXs and PGDH, the uterine enzymes involved in the biosynthesis and metabolism of prostanoids in the rat. We found that during pregnancy PGF(2alpha) production and also protein levels of COX-1 and COX-2 were decreased. The exogenous administration of P(4) significantly inhibited the uterine production of PGF(2alpha) and also the protein level of COX-2. PGF(2alpha), metabolism was assessed by PGDH activity, which resulted high during pregnancy and increased as a result of P(4) administration. These results indicate that PGs levels were negatively modulated by P(4), which could be exerting its effect by increasing PGs metabolism through stimulation on PGDH activity and an inhibition on COX and that is a major mechanism for maintain uterine quiescence in pregnancy.
Farina
M
M
Center of Pharmacological and Botanical Studies (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Serrano 669, Capital Federal, 1414 Buenos Aires, Argentina.
Ribeiro
M L
ML
Weissmann
C
C
Estevez
A
A
Billi
S
S
Vercelli
C
C
Franchi
A
A
D000020:Abortifacient Agents, Nonsteroidal / Q000378:metabolism*; D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015237:Dinoprost / Q000378:metabolism*; D005260:Female; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D000020:Abortifacient Agents, Nonsteroidal; D007527:Isoenzymes; D008565:Membrane Proteins; D011374:Progesterone; D015237:Dinoprost; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat