17α-Estradiol prevents ovariectomy-mediated obesity and bone loss

Abstract

Menopause is a natural physiological process in older women that is associated with reduced estrogen production and results in increased risk for obesity, diabetes, and osteoporosis. 17α-estradiol (17α-E2) treatment in males, but not females, reverses several metabolic conditions associated with advancing age, highlighting sexually dimorphic actions on age-related pathologies. In this study we sought to determine if 17α-E2 could prevent ovariectomy (OVX)-mediated detriments on adiposity and bone parameters in females. Eight-week-old female C57BL/6J mice were subjected to SHAM or OVX surgery and received dietary 17α-E2 during a six-week intervention period. We observed that 17α-E2 prevented OVX-induced increases in body weight and adiposity. Similarly, uterine weight and luminal cell thickness were decreased by OVX and prevented by 17α-E2 treatment. Interestingly, 17α-E2 prevented OVX-induced declines in tibial metaphysis cancellous bone. And similarly, 17α-E2 improved bone density parameters in both tibia and femur cancellous bone, primarily in OVX mice. In contrast, to the effects on cancellous bone, cortical bone parameters were largely unaffected by OVX or 17α-E2. In the non-weight bearing lumbar vertebrae, OVX reduced trabecular thickness but not spacing, while 17α-E2 increased trabecular thickness and reduced spacing. Despite this, 17α-E2 did improve bone volume/tissue volume in lumbar vertebrae. Overall, we found that 17α-E2 prevented OVX-induced increases in adiposity and changes in bone mass and architecture, with minimal effects in SHAM-operated mice. We also observed that 17α-E2 rescued uterine tissue mass and lining morphology to control levels without inducing hypertrophy, suggesting that 17α-E2 could be considered as an adjunct to traditional hormone replacement therapies.

17α-estradiol, a lifespan-extending compound, attenuates liver fibrosis by modulating collagen turnover rates in male mice

“…To investigate the effects of 17α-E2 on the development of liver fibrosis in mice, we administered CCl 4 to induce hepatotoxic stress while also providing 17α-E2 for the entire duration of the eight-week study (preventive group) or the final four weeks of the study (therapeutic group). Consistent with our previous reports 40-43,46,67,68 , 17α-E2 treatment reduced body mass at the conclusion of the study in both the preventive and therapeutic groups ( Fig. 2a ).…”

High-Fat Diet-Induced Obese Effects of Adipocyte-Specific CXCR2 Conditional Knockout in the Peritoneal Tumor Microenvironment of Ovarian Cancer

“…Thus, we first generated adipocyte-specific CXCR2 cKO mice by crossing C57BL/6- Cxcr2 tm1Rmra /J (JAX #024638) with B6.FVB-Tg (Adipoq-cre)1Evdr/J (JAX #028020) ( Figure 1 A). All mice were ovariectomized to avoid the suppressive effects of estrogen on obesity [ 28 , 29 ] and to create a pseudo-postmenopausal state, as most ovarian cancers develop after menopause. Before the intraperitoneal injection of ID8 OC cells, we confirmed the predominant expression levels of the CXCR2 protein in the adipose tissues from ND- and HFD-fed WT mice, but little expression of CXCR2 in ND- and HFD-fed cKO mice ( Figure 1 B and Figure S1 ).…”

Investigating the Effect of Hydroalcoholic Extract of Licorice Root to Prevent Ovariectomy-Mediated Complications

“…Aging is a natural phenomenon associated with a loss of sex hormones in women (menopause) [ 32 ]. It would be important to note that during the first year of menopause, women lose around 80% per year of their estrogens.…”