Regulation of Estrogen Receptor and Progesterone Receptor Expression by Estrogen and Progesterone/Progestogen in Human Umbilical Vein Endothelial Cells / 대한산부인과학회잡지

ABSTRACT

OBJECTIVE: Observational studies showed a significant reduction in cardiovascular disease (CVD) among postmenopausal hormone replacement therapy (HRT) users. But recent randomized clinical trial reported that HRT does not decrease, and may in fact, increase the incidence of CVD. Progestogen may in part contribute the increased risk but the exact role of different progestogens in the development of CVD is still unclear. The aim of this study was to investigate the effects of progesterone/progestogen and combination with estrogen on the regulation of estrogen and progesterone receptor m RNA expression in vascular endothelial cells to provide a basis to analyze the direct steroid effects on CVD. METHODS: Human Umbilical Vein Endothelial Cells (HUVEC) were cultured for 24 hours. Media were supplemented with estradiol (E2) (10(-7)M), progesterone (P4) (10(-7)M), medoxy-progesterone acetate (MPA) (10(-7)M), norethindrone acetate (NETA) (10(-7)M) and RU 486 (10(-6)M) alone or in combination. Receptor expression (estrogen receptor alpha and progesterone receptor total and isoform B) was examined at the mRNA level by reverse transcription-PCR. RESULTS: Total progesterone receptor expression was decreased after NETA treatment. E2, P4, MPA, NETA increased expression of PRB. PRB expression was more increased in E2 combined with P4 and MPA, than single treatment. PRB down regulation was found when RU 486 was additionally supplemented into the medium. ER expression was decreased after E2, P4, and MPA treatment. When MPA was added to E2, ER was more down reguated than the addition of P4 and NETA. RU 486 prevented down reguation of MPA on ER alpha. CONCLUSION: These findings suggested that MPA compared to P4 and NETA, may attenuate the favorable effect of estrogen on vasular endothelium.