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In the non\u2010pregnant adult, the mammary gland undergoes repeated cycles of proliferation and apoptosis in response to the fluctuating levels of oestrogen that occur during the reproductive stage. Oestrogen actions are mediated through the steroid hormone receptors, oestrogen receptor \u03b1 and \u03b2 and through a G\u2010protein coupled receptor. In the mammary gland, ER\u03b1 is of particular importance and thus will be highlighted. Mechanisms regulating oestrogen\u2010induced responses through ER\u03b1 are necessary to maintain homeostasis given that the signalling pathways that are activated in response to ER\u03b1\u2010mediated transcription can also induce transformation. ERK1\/2 and its downstream effector, p90 ribosomal S6 kinase (RSK), control homeostasis in the mammary gland by limiting oestrogen\u2010mediated ER\u03b1 responsiveness. ERK1\/2 drives degradation coupled ER\u03b1\u2010mediated transcription, whereas RSK2 acts as a negative regulator of ERK1\/2 activity to limit oestrogen responsiveness. Moreover, RSK2 acts as a positive regulator of translation. Thus, RSK2 provides both positive and negative signals to maintain oestrogen responsiveness. In addition to transmitting signals through tyrosine kinase receptors, ERK1\/2\u2010RSK engages with hedgehog signalling to maintain oestrogen levels and with the HIPPO pathway to regulate ER\u03b1\u2010mediated transcription. Additionally, ERK1\/2\u2010RSK controls the progenitor populations within the mammary gland to maintain the ER\u03b1\u2010positive population. RSK2 is involved in increased breast cancer risk in individuals taking oral contraceptives and in parity\u2010induced protection against breast cancer. RSK2 and ER\u03b1 may also co\u2010operate in diseases in tissues outside of the mammary gland.<\/jats:p>","DOI":"10.1111\/febs.16407","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T17:09:10Z","timestamp":1645117750000},"page":"1943-1953","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["ERK1\/2\u2010RSK regulation of oestrogen homeostasis"],"prefix":"10.1111","volume":"290","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9575-6801","authenticated-orcid":false,"given":"Eric B.","family":"Wright","sequence":"first","affiliation":[{"name":"Biomedical Engineering Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8380-9240","authenticated-orcid":false,"given":"Deborah A.","family":"Lannigan","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Vanderbilt University  Nashville 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