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J Clin Endocrinol Metab. 2017 Jun 1;102(6):1971-1982. doi: 10.1210/jc.2016-3153.

Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles.

Author information

1
Department of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, Kentucky 40536.
2
Department of Obstetrics and Gynecology, University of Gothenburg, 405 30 Gothenburg, Sweden.
3
Stockholm IVF, 112 81 Stockholm, Sweden.
4
Bluegrass Fertility Center, Lexington, Kentucky 40503.

Abstract

Context:

In animal models, the luteinizing hormone surge increases progesterone (P4) and progesterone receptor (PGR), prostaglandins (PTGs), and epidermal growth factor (EGF)-like factors that play essential roles in ovulation. However, little is known about the expression, regulation, and function of these key ovulatory mediators in humans.

Objective:

To determine when and how these key ovulatory mediators are induced after the luteinizing hormone surge in human ovaries.

Design and Participants:

Timed periovulatory follicles were obtained from cycling women. Granulosa/lutein cells were collected from in vitro fertilization patients.

Main Outcome Measures:

The in vivo and in vitro expression of PGR, PTG synthases and transporters, and EGF-like factors were examined at the level of messenger RNA and protein. PGR binding to specific genes was assessed. P4 and PTGs in conditioned media were measured.

Results:

PGR, PTGS2, and AREG expressions dramatically increased in ovulatory follicles at 12 to 18 hours after human chorionic gonadotropin (hCG). In human granulosa/lutein cell cultures, hCG increased P4 and PTG production and the expression of PGR, specific PTG synthases and transporters, and EGF-like factors, mimicking in vivo expression patterns. Inhibitors for P4/PGR and EGF-signaling pathways reduced hCG-induced increases in PTG production and the expression of EGF-like factors. PGR bound to the PTGS2, PTGES, and SLCO2A1 genes.

Conclusions:

This report demonstrated the time-dependent induction of PGR, AREG, and PTGS2 in human periovulatory follicles. In vitro studies indicated that collaborative actions of P4/PGR and EGF signaling are required for hCG-induced increases in PTG production and potentiation of EGF signaling in human periovulatory granulosa cells.

PMID:
28323945
PMCID:
PMC5470773
DOI:
10.1210/jc.2016-3153
[Indexed for MEDLINE]
Free PMC Article

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