The Effect of Progesterone on Myometrial Contractility, Potassium Channels, and Tocolytic Efficacy

Anderson, Laurie; Martin, William J.; Higgins, Claire A.; Nelson, Scott M.; Norman, Jane E.

doi:10.1177/1933719109340926

Cited by 49 publications

(54 citation statements)

References 29 publications

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“…Similar observations have been reported by Sexton et al 45 and Anderson et al 46 Studies in pregnant mice indicate that progesterone (but not 17-OHPC) could prevent preterm delivery. 47 However, the effects of the 2 compounds are complex and dependent on the route of administration, and the vehicle used.…”

Section: Differences Between Progesterone and 17α-hydroxyprogesteronesupporting

confidence: 86%

Progesterone is not the same as 17α-hydroxyprogesterone caproate: implications for obstetrical practice

Romero

Stanczyk

2013

American Journal of Obstetrics and Gynecology

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Section: Differences Between Progesterone and 17α-hydroxyprogesteronesupporting

confidence: 86%

Progesterone is not the same as 17α-hydroxyprogesterone caproate: implications for obstetrical practice

Romero

Stanczyk

2013

American Journal of Obstetrics and Gynecology

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“…The findings from these studies are summarized in Table III. The relaxing effect occurs only in pharmacological concentrations (micromolar) and is rapid, suggesting non-genomic mechanism of action (Perusquia et al , 1990; Anderson et al , 2009; Tica et al , 2011). A logical assumption would be that the observed effect of androgens might not occur physiologically because physiological androgen concentrations are in a nanomolar range.…”

Section: Resultsmentioning

confidence: 99%

Androgens in pregnancy: roles in parturition

Makieva

Saunders

Norman

2014

Human Reproduction Update

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186

143

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BACKGROUNDUnderstanding the physiology of pregnancy enables effective management of pregnancy complications that could otherwise be life threatening for both mother and fetus. A functional uterus (i) retains the fetus in utero during pregnancy without initiating stretch-induced contractions and (ii) is able to dilate the cervix and contract the myometrium at term to deliver the fetus. The onset of labour is associated with successful cervical remodelling and contraction of myometrium, arising from concomitant activation of uterine immune and endocrine systems. A large body of evidence suggests that actions of local steroid hormones may drive changes occurring in the uterine microenvironment at term. Although there have been a number of studies considering the potential role(s) played by progesterone and estrogen at the time of parturition, the bio-availability and effects of androgens during pregnancy have received less scrutiny. The aim of this review is to highlight potential roles of androgens in the biology of pregnancy and parturition.METHODSA review of published literature was performed to address (i) androgen concentrations, including biosynthesis and clearance, in maternal and fetal compartments throughout gestation, (ii) associations of androgen concentrations with adverse pregnancy outcomes, (iii) the role of androgens in the physiology of cervical remodelling and finally (iv) the role of androgens in the physiology of myometrial function including any impact on contractility.RESULTSSome, but not all, androgens increase throughout gestation in maternal circulation. The effects of this increase are not fully understood; however, evidence suggests that increased androgens might regulate key processes during pregnancy and parturition. For example, androgens are believed to be critical for cervical remodelling at term, in particular cervical ripening, via regulation of cervical collagen fibril organization. Additionally, a number of studies highlight potential roles for androgens in myometrial relaxation via non-genomic, AR-independent pathways critical for the pregnancy reaching term. Understanding of the molecular events leading to myometrial relaxation is an important step towards development of novel targeted tocolytic drugs.CONCLUSIONSThe increase in androgen levels throughout gestation is likely to be important for establishment and maintenance of pregnancy and initiation of parturition. Further investigation of the underlying mechanisms of androgen action on cervical remodelling and myometrial contractility is needed. The insights gained may facilitate the development of new therapeutic approaches to manage pregnancy complications such as preterm birth.

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“…Importantly, the effects of progesterone on connexin 43 expression do not become apparent until several hours after drug administration. 24,26 Thus, they are unlikely to account for the acute tocolytic effect of progesterone that we and others have shown in vitro, 30,31 suggesting that progesterone has additional nongenomic effects on uterine contractility. The effects of progesterone administration on connexin 26, EP2, and eNOS observed ex vivo were not replicated in our in …”

Section: Discussionmentioning

confidence: 76%

Effect of Prolonged In Vivo Administration of Progesterone in Pregnancy on Myometrial Gene Expression, Peripheral Blood Leukocyte Activation, and Circulating Steroid Hormone Levels

et al. 2011

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The Effect of Progesterone on Myometrial Contractility, Potassium Channels, and Tocolytic Efficacy

Abstract: Progesterone exerts rapid inhibition of the amplitude of myometrial contractions in vitro but 17OHPC does not. The action of progesterone does not appear to operate via potassium channels nor does it enhance the activity of certain tocolytic drugs.

Cited by 49 publications

References 29 publications

Progesterone is not the same as 17α-hydroxyprogesterone caproate: implications for obstetrical practice

Progesterone is not the same as 17α-hydroxyprogesterone caproate: implications for obstetrical practice

Androgens in pregnancy: roles in parturition

Effect of Prolonged In Vivo Administration of Progesterone in Pregnancy on Myometrial Gene Expression, Peripheral Blood Leukocyte Activation, and Circulating Steroid Hormone Levels

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