TY - JOUR
T1 - Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary
AU - Nallasamy, Shanmugasundaram
AU - Kim, Jaeyeon
AU - Sitruk-Ware, Regine
AU - Bagchi, Milan
AU - Bagchi, Indrani
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: a grant from the NICHD/NIH U54 HD 29990 . This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR16515-01 from the National Center for Research Resources, National Institutes of Health (I.C.B.).
PY - 2013/4
Y1 - 2013/4
N2 - Ulipristal acetate (UPA), a progesterone receptor (PR) modulator, is used as an emergency contraceptive in women. Here, using a mouse model, we investigated the mechanism of action of UPA as an ovulation blocker. In mice, ovulation is induced ∼12 hours following the treatment with exogenous gonadotropins, including human chorionic gonadotropin (hCG), which mimics the action of luteinizing hormone (LH). When administered within 6 hours of hCG treatment, UPA is a potent blocker of ovulation. However, UPA's effectiveness declined significantly when it was given at 8 hours post hCG. Our study revealed that, when administered within 6 hours of hCG, UPA blocks ovulation by inhibiting PR-dependent pathways intrinsic to the ovary. At 8 hours post hCG, when the PR signaling has already occurred, UPA is unable to block ovulation efficiently. Collectively, these results indicated that UPA, when administered within a critical time window following the LH surge, blocks PR-dependent pathways in the ovary to function as an effective antiovulatory contraceptive.
AB - Ulipristal acetate (UPA), a progesterone receptor (PR) modulator, is used as an emergency contraceptive in women. Here, using a mouse model, we investigated the mechanism of action of UPA as an ovulation blocker. In mice, ovulation is induced ∼12 hours following the treatment with exogenous gonadotropins, including human chorionic gonadotropin (hCG), which mimics the action of luteinizing hormone (LH). When administered within 6 hours of hCG treatment, UPA is a potent blocker of ovulation. However, UPA's effectiveness declined significantly when it was given at 8 hours post hCG. Our study revealed that, when administered within 6 hours of hCG, UPA blocks ovulation by inhibiting PR-dependent pathways intrinsic to the ovary. At 8 hours post hCG, when the PR signaling has already occurred, UPA is unable to block ovulation efficiently. Collectively, these results indicated that UPA, when administered within a critical time window following the LH surge, blocks PR-dependent pathways in the ovary to function as an effective antiovulatory contraceptive.
KW - contraception
KW - ovulation
KW - progesterone receptor
KW - ulipristal acetate
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U2 - 10.1177/1933719112459239
DO - 10.1177/1933719112459239
M3 - Article
C2 - 23012316
AN - SCOPUS:84875746014
SN - 1933-7191
VL - 20
SP - 371
EP - 381
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 4
ER -