Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, United States; Laboratory of Neuroendocrinology of the Brain Research Institute, University of California Los Angeles, Los Angeles, United States
Jae Whan Park
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, United States; Laboratory of Neuroendocrinology of the Brain Research Institute, University of California Los Angeles, Los Angeles, United States
In Sook Ahn
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, United States
Graciel Diamante
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, United States
Nilla Sivakumar
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, United States; Laboratory of Neuroendocrinology of the Brain Research Institute, University of California Los Angeles, Los Angeles, United States
Douglas Arneson
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, United States
Xia Yang
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, United States
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, United States; Laboratory of Neuroendocrinology of the Brain Research Institute, University of California Los Angeles, Los Angeles, United States
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, United States; Laboratory of Neuroendocrinology of the Brain Research Institute, University of California Los Angeles, Los Angeles, United States
Adjuvant tamoxifen therapy improves survival in breast cancer patients. Unfortunately, long-term treatment comes with side effects that impact health and quality of life, including hot flashes, changes in bone density, and fatigue. Partly due to a lack of proven animal models, the tissues and cells that mediate these negative side effects are unclear. Here, we show that mice undergoing tamoxifen treatment experience changes in temperature, bone, and movement. Single-cell RNA sequencing reveals that tamoxifen treatment induces widespread gene expression changes in the hypothalamus and preoptic area (hypothalamus-POA). These expression changes are dependent on estrogen receptor alpha (ERα), as conditional knockout of ERα in the hypothalamus-POA ablates or reverses tamoxifen-induced gene expression. Accordingly, ERα-deficient mice do not exhibit tamoxifen-induced changes in temperature, bone, or movement. These findings provide mechanistic insight into the effects of tamoxifen on the hypothalamus-POA and indicate that ERα mediates several physiological effects of tamoxifen treatment in mice.
