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Effects in vitro of progesterone and two 5 alpha-reduced progestins, 5 alpha-pregnane-3,20-dione and 5 alpha-pregnane-3 alpha-ol-20-one, on contracting human myometrium at term
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
1992 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 71, no 1, 28-33 p.Article in journal (Refereed) Published
Abstract [en]

Progesterone is known to prevent labour at term in domestic animals, but its effect in primates is uncertain. 5 alpha-reduced progesterone metabolites are more potent central nervous system depressants than progesterone is itself. Progesterone and its 5 alpha-reduced metabolites also relax pregnant rat myometrium in vitro. The serum concentration of the initial 5 alpha-reduced metabolite, 5 alpha-pregnane-3,20-dione, is high during pregnancy, but decreases significantly prior to parturition. The next metabolite, 5 alpha-pregnane-3 alpha-ol-20-one, has anaesthetic properties in human beings. The purpose of this study was to ascertain whether these progesterone metabolites also suppress contracting human uterine muscle at term. An in vitro model was devised. Strips of human myometrial muscle were mounted in organ chambers and after regular contractions had become established, the strips were superfused with progestin solutions. The progestins were dissolved in the buffer using an ultrasound bath. Progesterone, used as reference substance, slightly reduced the measured amount of muscular work performed per contraction, recordable after 18 min of exposure (p less than 0.05). Similar results have been reported previously in the literature; 5 alpha-pregnane-3 alpha-ol-20-one showed the same tendency though not significant at the 5% level. 5 alpha-pregnane-3,20-dione evidently reduced the contraction frequency after 10 min of exposure (p less than 0.05). None of the substances affected the duration of the contraction. These 5 alpha-reduced progesterone metabolites are thus not potent inhibitors of contracting human term myometrium in vitro.

Place, publisher, year, edition, pages
1992. Vol. 71, no 1, 28-33 p.
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:umu:diva-46972PubMedID: 1315093OAI: oai:DiVA.org:umu-46972DiVA: diva2:441641
Available from: 2011-09-17 Created: 2011-09-17 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Progesterone in human parturition: progesterone and 5α-pregnane-3,20-dione in relation to human myometrial activity
Open this publication in new window or tab >>Progesterone in human parturition: progesterone and 5α-pregnane-3,20-dione in relation to human myometrial activity
1991 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This study was undertaken to evaluate the relationship of progesterone and 5α-pregnane-3,20-dione (5αDHP), a major progesterone metabolite, to human parturition. The serum concentrations of 5αDHP prior to, during and following parturition were to be established, as well as its maternal and fetal concentration in different modes of delivery. Some of its effects in vitro were also to be studied. Progesterone was included primarily as a reference substance. 5α-pregnane-3α-ol-20-one (3αOH-DHP), a potent CNS depressant progesterone metabolite, was included in the in vitro study.

Progesterone: The maternal serum concentration of progesterone is stable during the last three weeks of pregnancy preceding spontaneous labor and through labor. The various modes of delivery studied were elective cesarean section; ocytocin resistant fuctional dystocia; normal, effective, induced labor; and normal, effective, spontaneous labor. The serum progesterone concentrations in dystocia and at elective cesarean section were lower than during normal labor (P<0.005 - p<0.001). Women with ineffectual or no labor at all had progesterone concentrations ranging between 77 and 48% in maternal serum and for umbilical cord serum 65-43% of those at normal labor. In normal labor, primiparous women had higher progesterone concentrations than parous women. When scrutinizing the literature, similar results were found, though interpreted differently. In the in vitro model, human term myometrial muscle strips constantly exposed to progesterone started to contract later (p<0.005), but with a higher frequency (p<0.01) than parallel controls deprived of progesterone. A new property of progesterone emerges when these results are combined with findings in the literature regarding progesterone. Progesterone in high concentrations are related to normal, effective labor.

5α-pregnane-3,20-dione (5αDHP): Mean serum 5αDHP concentrations declined significantly during the last week of pregnancy (p<0.005). During labor, the maternal 5αDHP serum concentration remained stable. No distinct differences according to parity or mode of delivery were evident. The 5αDHP serum concentration in the fetal compartment was double that in the maternal compartment. 5αDHP had only minor effects in the in vitro model. These findings suggest a minor change in 5αDHP production preceding the onset of spontaneous labor, which could contribute to the increased progesterone concentration noted.

5α-pregnane-3α-ol-20-one (3αOH-DHP): No major effects of 3αOH-DHP were seen in the in vitro model. Thus unlikely that it hampers myometrial smooth muscle activity.

In conclusion: Two generally accepted effects of progesterone in relation to parturition are; Decreasing concentrations induce labor while stable or increasing concentrations do have pregnancy maintaining properties. This study suggests a third property of progesterone in relation to human parturition. High and increasing progesterone concentrations seem to have uterotonic properties.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 1991. 41 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 321
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-46974 (URN)91-7174-623-4 (ISBN)
Public defence
1991-11-22, Hörsal B (Rosa salen), by 1D, Umeå regionsjukhus, 14:00 (English)
Available from: 2011-09-17 Created: 2011-09-17 Last updated: 2011-09-17Bibliographically approved

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