Korean J Obstet Gynecol.  2003 Dec;46(12):2352-2359.

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

• Lee WJ
• Cho SH

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.

Keyword

Hormone replacement therapy; Estrogen receptor; Progesterone receptor; Human umbilical vein endothelial cell

MeSH Terms

Cardiovascular Diseases
Down-Regulation
Endothelial Cells
Endothelium
Estradiol
Estrogen Replacement Therapy
Estrogens*
Female
Hormone Replacement Therapy
Human Umbilical Vein Endothelial Cells*
Humans*
Incidence
Mifepristone
Norethindrone
Progesterone*
Progestins
Receptors, Progesterone*
RNA
RNA, Messenger
Estradiol
Estrogens
Mifepristone
Norethindrone
Progesterone
Progestins
RNA
RNA, Messenger
Receptors, Progesterone