Scholarlink

<p>17α-estradiol (17α-E2) extends median lifespan and improves metabolic homeostasis in male mice through estrogen receptor α (ERα)-dependent mechanisms, but female mice are largely unresponsive unless ovariectomized or subjected to chronic high-fat feeding. Whether the gradual hormonal transition of natural reproductive aging similarly unmasks female responsiveness to 17α-E2 remains unknown. We tested whether 4-vinylcyclohexene diepoxide (VCD)-induced depletion of the ovarian reserve would render female mice responsive to 17α-E2 by treating wild-type (WT) and ERα knockout (ERαKO) littermates with VCD followed by 16 weeks of 17α-E2 administration. VCD-induced estropause was confirmed by elevated FSH, anestrus, and reduced ovarian size, but did not adversely affect metabolic phenotypes in WT mice. 17α-E2 treatment elicited modest improvements in adiposity and glucose tolerance, suppressed circulating IL-1β and IL-6, and reversed estropause-induced uterine atrophy in WT mice, but failed to rescue endometrial fibrosis. All 17α-E2-mediated effects were absent in ERαKO mice. These findings demonstrate that estropause does not unmask broad female responsiveness to 17α-E2 and indicate that the sex-specific actions of 17α-E2 extend beyond competitive receptor occupancy by endogenous 17β-E2.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

VCD-induced estropause fails to enhance responsiveness to 17α-estradiol in adult female mice

  • 期刊论文

  • 发表日期：

    2026年7月22日

查看全文
  • Sean R. Janovic,
  • Roberto Santín-Márquez,
  • José V. V. Isola,
  • Camila R. C. de Brito,
  • Roshini Sathiaseelan,
  • Jessica D. Hense,
  • Subhasri Biswas,
  • Heather C. Rice,
  • Samim A. Mondal,
  • Michael B. Stout

摘要

17α-estradiol (17α-E2) extends median lifespan and improves metabolic homeostasis in male mice through estrogen receptor α (ERα)-dependent mechanisms, but female mice are largely unresponsive unless ovariectomized or subjected to chronic high-fat feeding. Whether the gradual hormonal transition of natural reproductive aging similarly unmasks female responsiveness to 17α-E2 remains unknown. We tested whether 4-vinylcyclohexene diepoxide (VCD)-induced depletion of the ovarian reserve would render female mice responsive to 17α-E2 by treating wild-type (WT) and ERα knockout (ERαKO) littermates with VCD followed by 16 weeks of 17α-E2 administration. VCD-induced estropause was confirmed by elevated FSH, anestrus, and reduced ovarian size, but did not adversely affect metabolic phenotypes in WT mice. 17α-E2 treatment elicited modest improvements in adiposity and glucose tolerance, suppressed circulating IL-1β and IL-6, and reversed estropause-induced uterine atrophy in WT mice, but failed to rescue endometrial fibrosis. All 17α-E2-mediated effects were absent in ERαKO mice. These findings demonstrate that estropause does not unmask broad female responsiveness to 17α-E2 and indicate that the sex-specific actions of 17α-E2 extend beyond competitive receptor occupancy by endogenous 17β-E2.

Graphical abstract