Masami Uji

Estrogen Replacement Suppresses Pressor Response and Oxidative Stress Induced by Cage-switch Stress in Ovariectomized Rats

We examined the suppressive effects of estradiol on psychological stress–induced cardiovascular responses and oxidative stress in ovariectomized rats, both placebo‐treated (OVX+Pla) and estrogen‐treated (OVX+E2). The elevations in blood pressure and heart rate induced by cage‐switch stress were attenuated in the OVX+E2 as compared with the OVX+Pla group. NG‐nitro‐L‐arginine methyl ester, administered via drinking water, reduced the difference in these responses. Furthermore, this stress increased plasma nitrotyrosine and decreased plasma nitric oxide (NO) metabolites only in the OVX+Pla group. We demonstrated that estrogen replacement suppresses cardiovascular responses to psychological stress, at least in part by improving NO bioavailability in ovariectomized rats.

Estrogen replacement enhances insulin-induced AS160 activation and improves insulin sensitivity in ovariectomized rats.

Menopause predisposes women to impaired glucose metabolism, but the role of estrogen remains unclear. In this study, we examined the effects of chronic estrogen replacement on whole body insulin sensitivity and insulin signaling in ovariectomized rats. Female Wistar rats aged 9 wk were ovariectomized under anesthesia. After 4 wk, pellets containing either 17β-estradiol (E2) or placebo (Pla) were subcutaneously implanted in the rats. After 4 wk of treatment, the intra-abdominal fat accumulation was greater in the Pla group than that in the E2 group. Hyperinsulinemic-euglycemic clamp analysis and intravenous glucose tolerance test revealed that insulin sensitivity was significantly lower in the Pla group than in the E2 group. In addition, Western blotting showed that in vivo insulin stimulation increased protein kinase B (Akt) phosphorylation to a similar degree in the gastrocnemius and liver of both groups, but phosphorylated Akt2 Ser474 was enhanced in the muscle of the E2 group compared with the Pla group. Moreover, insulin-stimulated phosphorylation of Akt substrate of 160 kDa (AS160) Thr642 was observed only in the E2 group, resulting in the difference between the two groups. Additionally, AS160 protein and mRNA levels were higher in muscle of the E2 group than the Pla group. In contrast, E2 replacement had no effect on glucose transporter 4 protein levels in muscle and glycogen synthase kinase-3β in muscle and liver. These results suggest that estrogen replacement improves insulin sensitivity by activating the Akt2/AS160 pathway in the insulin-stimulated muscle of ovariectomized rats.