August 6, 2020

The importance of estrogen cycles

Deborah Lannigan and colleagues identify a key regulator of the estrogen receptor and suggest that its downregulation by oral contraceptives may increase oxidative stress and DNA damage, a common cause of cancer.

by Sarah E. Glass

Oral contraceptives are implicated in slightly increasing breast cancer risk. This birth control method contains forms of estrogen, a hormone that binds ERalpha (estrogen receptor alpha), to alter the reproductive cycle. While much is known about estrogen signaling, few have researched how receptor homeostasis is maintained to ensure regular cycling. 

Deborah Lannigan, PhD, and colleagues discovered that RSK2, a potential tumor-suppressor protein, is integral for ERalpha levels when comparing reproductive tissues of wild-type and RSK2 knockout mice. 

Further analysis by mammary gland staining showed that RSK2 maintains receptor homeostasis, and therefore regular cycling, by reducing oxidative stress. These findings were supported in a cohort of women using oral contraceptives, as they had lower levels of RSK2 than a control group. 

In the journal Cell Reports, the researchers identified RSK2 as a key regulator of the estrogen receptor and suggested that its downregulation by contraceptive use can increase DNA damage, a common cause of cancer, via oxidative stress.

The study was supported by National Institutes of Health grants DK113423, CA213201, AI144196 and AI142040, and by the National Science Foundation.