Dihydrotestosterone induces arterial stiffening in female mice

Autor: Alec C. Horton, Mary M. Wilkinson, Isabella Kilanowski-Doroh, Zhejun Dong, Jiao Liu, Benard O. Ogola, Bruna Visniauskas, Sarah H. Lindsey
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Biology of Sex Differences, Vol 15, Iss 1, Pp 1-12 (2024)
Druh dokumentu: article
ISSN: 2042-6410
DOI: 10.1186/s13293-024-00586-3
Popis: Abstract Background Androgens are important sex hormones in both men and women and are supplemented when endogenous levels are low, for gender transitioning, or to increase libido. Androgens also circulate at higher levels in women with polycystic ovarian syndrome, a condition that increases the risk for cardiovascular diseases including hypertension and arterial stiffness. Since our previous work shows an important role for the G protein-coupled estrogen receptor (GPER) in arterial stiffness, we hypothesized that other hormones including androgens may impact arterial stiffness in female mice via downregulation of GPER. Methods The impact of the non-aromatizable androgen dihydrotestosterone (DHT), the glucocorticoid dexamethasone, and the progestin medroxyprogesterone acetate (all 100 nM for 24 h) on GPER and ERα expression was assessed in cultured vascular smooth muscle cells using droplet digital PCR (ddPCR). To assess the in vivo impact of the DHT-induced downregulation of GPER, female ovary-intact C57Bl/6 mice at 15–16 weeks of age were treated with silastic capsules containing DHT for 4 weeks, one with a dosage expected to mimic human male DHT levels and another to double the expected human concentration (n = 8–9/group). Results In cultured vascular smooth muscle cells, GPER mRNA was decreased by DHT (P = 0.001) but was not impacted by dexamethasone or medroxyprogesterone. In contrast, ERα expression in cultured cells was significantly suppressed by all three hormones (P
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