2-Methoxyestradiol in the human corpus luteum throughout the luteal phase and its influence on lutein cell steroidogenesis and angiogenic activity

Abstract

Objective: To quantitate 2-methoxyestradiol (2-ME) in human corpus luteum (CL) of different ages and to determine the expression of cytochrome-P450-1A1 (CYP1A1) and catechol-O-methyl transferase (COMT) in CL and the action of 2-ME on P, vascular endothelial growth factor (VEGF) secretion, and luteal angiogenesis.

Design: Experimental study.

Setting: University division of reproductive endocrinology.

Patient(s): Twenty-four women of reproductive age.

Intervention(s): CL was collected from 15 women during the minilaparotomy for tubal sterilization. Granulosa lutein cells were harvested 36 hours after hCG administration in patients undergoing IVF.

Main outcomes measure(s): Levels of 2-ME were determined by high-performance liquid chromatography in CL. CYP1A1 and COMT were assessed by immunohistochemistry and Western blot. P and VEGF were measured by radioimmunoassay and ELISA. The angiogenic potential was analyzed using EA.hy926 cells.

Result(s): Plasma levels of E₂ decreased in the late luteal phase in association with an increase in luteal tissue of 2-ME concentrations. Concomitantly, there was a significant reduction of angiogenic activity in late CL. There was no significant variation in CYP1A1 and COMT expression in all CL. In physiological doses, 2-ME inhibited basal VEGF by granulosa lutein cells and diminished the angiogenic activity in conditioned media but did not prevent P and VEGF production stimulated by hCG.

Conclusion(s): These data suggest the participation of 2-ME in physiological luteolysis by reducing angiogenesis. However, 2-ME did not prevent in vitro hCG stimulation of P biosynthesis, providing a mechanism for CL rescue in the cycle of conception.

Keywords: 2-methoxyestradiol; angiogenic potential; human corpus luteum; vascular endothelial growth factor.