Estrogen Receptor β Contributes to Both Hypertension and Hypothalamic Plasticity in a Mouse Model of Peri-Menopause
| Autor: | Fangmin Yu, Gang Wang, Elizabeth M. Waters, Natalina H. Contoreggi, Megan A. Johnson, Clara Woods, Bruce S. McEwen, Michael J. Glass, Teresa A. Milner, Sanoara Mazid, Kenneth S. Korach, Tracey A. Van Kempen |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Agonist medicine.medical_specialty medicine.drug_class Estrogen receptor Mice 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Estrogen Receptor beta Research Articles Neuronal Plasticity business.industry General Neuroscience Neurogenic hypertension medicine.disease Angiotensin II Perimenopause Mice Inbred C57BL Menopause Disease Models Animal 030104 developmental biology Endocrinology Blood pressure Estrogen Hypertension Female business hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Paraventricular Hypothalamic Nucleus Hormone |
| Zdroj: | J Neurosci |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.0164-21.2021 |
| Popis: | Hypertension susceptibility in women increases at the transition to menopause, termed perimenopause, a state characterized by erratic estrogen fluctuation and extended hormone cycles. Elucidating the role of estrogen signaling in the emergence of hypertension during perimenopause has been hindered by animal models that are confounded by abrupt estrogen cessation or effects of aging. In the present study, accelerated ovarian failure (AOF) in estrogen receptor β (ERβ) reporter mice was induced by 4-vinylcyclohexene diepoxide in young mice to model early-stage ovarian failure (peri-AOF) characteristic of peri-menopause. It was found that administering ERβ agonists suppressed elevated blood pressure in a model of neurogenic hypertension induced by angiotensin II (AngII) in peri-AOF, but not in age-matched male mice. It was also found that ERβ agonist administration in peri-AOF females, but not males, suppressed the heightened NMDAR signaling and reactive oxygen production in ERβ neurons in the hypothalamic paraventricular nucleus (PVN), a critical neural regulator of blood pressure. It was further shown that deleting ERβ in the PVN of gonadally intact females produced a phenotype marked by a sensitivity to AngII hypertension. These results suggest that ERβ signaling in the PVN plays an important role in blood pressure regulation in female mice and contributes to hypertension susceptibility in females at an early stage of ovarian failure comparable to human perimenopause. |
| Databáze: | OpenAIRE |
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