Functional effects of 17alpha-hydroxyprogesterone caproate (17P) on human myometrial contractility in vitro.
BACKGROUND
17 alpha-hydroxyprogesterone caproate (17P) administration reportedly improves outcome for women with a previous spontaneous preterm delivery. This study, using in vitro strips of human uterine smooth muscle, aimed to investigate the direct non-genomic effects of 17P on spontaneous and induced contractions in tissues obtained during pregnancy, and in the non-pregnant state.


METHODS
Biopsies of human myometrium were obtained at elective cesarean section, and from hysterectomy specimens, and dissected strips suspended for isometric recordings. The effects of 17P (1 nmol/L -10 micro mol/L) on spontaneous and agonist-induced (oxytocin 0.5 nmol/L for pregnant, phenylephrine 10 micromol/L for non-pregnant) contractions were measured. Integrals of contractile activity, including the mean maximal inhibition values (MMI) observed at the maximal concentration, were compared with those from simultaneously run control strips.


RESULTS
There was no significant direct effect exerted by 17P on pregnant or non-pregnant human myometrial contractility. The MMI +/- SEM for spontaneous contractions in pregnant myometrium was 4.9% +/- 7.2 (n = 6; P = 0.309) and for oxytocin-induced contractions was 2.2% +/- 1.3 (n = 6; P = 0.128). For non-pregnant myometrium, the MMI +/- SEM for spontaneous contractions was 8.8% +/- 11.0 (n = 6; P = 0.121) and for phenylephrine induced contractions was -7.9% +/- 6.5 (n = 6; P = 0.966).


CONCLUSIONS
The putative benefits of 17P for preterm labor prevention are not achieved, even partially, by a direct utero-relaxant effect. These findings outline the possibility that genomic effects of 17P, achieved over long periods of administration, are required for its reported therapeutic benefits.
Sexton
Donal J
DJ
Department of Obstetrics and Gynaecology, National University of Ireland Galway, Clinical Science Institute, University College Hospital, Newcastle Road, Galway, Ireland. donalsexton0@hotmail.com <donalsexton0@hotmail.com>
O'Reilly
Michael W
MW
Friel
Anne M
AM
Morrison
John J
JJ
D000077713:17 alpha-Hydroxyprogesterone Caproate; D001706:Biopsy; D002585:Cesarean Section; D005260:Female; D006801:Humans; D006908:Hydroxyprogesterones / Q000494:pharmacology*; D007044:Hysterectomy; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects* / Q000502:physiology*; D010121:Oxytocin / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D014590:Uterine Contraction / Q000187:drug effects*
D006908:Hydroxyprogesterones; D010656:Phenylephrine; D000077713:17 alpha-Hydroxyprogesterone Caproate; D010121:Oxytocin