The progesterone antagonist onapristone increases the effectiveness of oxytocin to produce delivery without changing the myometrial oxytocin receptor concentrations.
The progesterone antagonist onapristone was used in guinea pigs during late pregnancy (43 +/- 2 days after coitus) and before term (day 61 after coitus) to investigate the role of progesterone on uterine reactivity to exogenous oxytocin, concentration of oxytocin receptors, and gap junctions in the myometrium. Onapristone priming increased the ability of oxytocin to induce delivery during late pregnancy and before term by factors of greater than or equal to 30 and approximately 10, respectively. The intrauterine pressure recording on day 43 after coitus revealed phasic, laborlike contractions in response to oxytocin in onapristone-treated animals, in contrast to tonic reactions in controls. The increase in the oxytocin response in onapristone-treated animals was not associated with an increase in myometrial oxytocin receptor concentrations either during late pregnancy or before term. By contrast, treatment with onapristone significantly decreased the input resistance of myometrial cells in guinea pigs in late pregnancy (43 +/- 1 day after coitus) to the level of animals at term. This was associated with a marked increase in myometrial gap junctions stained with antibodies against connexin 43. These results indicate that progesterone may control myometrial reactivity to oxytocin in pregnant guinea pigs by effects on postreceptor events mainly by suppressing the gap junctions.
Chwalisz
K
K
Research Laboratories of Schering AG, Berlin, Germany.
Fahrenholz
F
F
Hackenberg
M
M
Garfield
R
R
Elger
W
W
D000818:Animals; D017630:Connexins; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004594:Electrophysiology; D005260:Female; D005865:Gestational Age; D006067:Gonanes / Q000494:pharmacology*; D006168:Guinea Pigs; D007365:Intercellular Junctions / Q000187:drug effects*; D007751:Labor, Induced; D008565:Membrane Proteins; D015735:Mifepristone / Q000494:pharmacology; D009215:Myometrium / Q000737:chemistry / Q000187:drug effects*; D010121:Oxytocin / Q000494:pharmacology*; D011374:Progesterone / Q000037:antagonists & inhibitors*; D011945:Receptors, Angiotensin / Q000032:analysis / Q000187:drug effects*; D018045:Receptors, Oxytocin; D014590:Uterine Contraction
D017630:Connexins; D006067:Gonanes; D008565:Membrane Proteins; D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; D015735:Mifepristone; D011374:Progesterone; D010121:Oxytocin; C053238:onapristone