Estrogen receptors

The estrogen receptor (ER) is the receptor of estrogens like estradiol. Agonists of the ER include estradiol, ethinylestradiol, and conjugated estrogens. Partial agonists of the ER, or selective estrogen receptor modulators, include tamoxifen, clomifene, and raloxifene. Antagonists of the ER include fulvestrant.

There are two different forms of the estrogen receptor, ERα and ERβ. ERβ may have anti-proliferative effects that oppose the effects of ERα.

Regulation
In MCF-7 breast cancer cells, administration of estradiol suppressed estrogen receptor α (ERα) levels by about 60% after 6 hours. ERα mRNA expression was transiently decreased by about 90%. ERα expression returned to normal in 24-48 hours. ERα gene transcription was suppressed by 90% after 1 hour, then increased to 2x its original rate after 3-6 hours, remaining elevated for at least 48 hours. This suggests that downregulation of ERα by estradiol occurs both at transcription and post-transcription.

Tamoxifen did not upregulate or downregulate ERα. When administered concurrently with estradiol, it prevented the downregulation of ERα by estradiol.

The following table summarizes the regulatory effects of various agents on ERα: a Breast cancer cell line.

b Peripheral blood mononuclear cell.

c Ovarian tissue studied in isolation; HPG axis is not taken into account.

d Comparing with the effect of estradiol alone, this suggests that testosterone alone would result in a decrease of ERα mRNA expression.

e The increase in mRNA expression with estradiol and progesterone is less than the increase with estradiol alone, suggesting that progesterone alone inhibits ERα mRNA expression. This hypothesis is supported by the effect of other progestogens on ERα mRNA expression.

f Paper does not specify which GnRH agonist was used.