Chronic 17Beta‐Estradiol Supplementation Reduces Blood Pressure and Alters Renal Estrogen Receptor Expression in Female Growth‐Restricted Rats in Later Life
Authors: Davis Gwendolyn K. , Cole Alyssa , Newsome Ashley D. , Ojeda Norma B. , Alexander Barbara T. 
Published: June 2021

The role of estrogen in mediating protective cardiovascular (CV) effects in menopausal women is controversial. The prevalence of hypertension in women born low birth weight is two‐fold greater at the age of 60 relative to normal birth weight women. In addition, low birth weight women exhibit increased adiposity by middle‐age and an earlier age at menopause. In our model of intrauterine growth restriction (IUGR) induced by placental insufficiency in the pregnant rat, female IUGR offspring have an elevated blood pressure (BP) at 12 months of age that is associated with increased adiposity. Female IUGR also exhibit reproductive senescence by 12 months of age, or 6 months prior to female control, resulting in a shift in the estradiol to testosterone ratio. To determine the importance of estradiol on the CV profile in female IUGR, we tested the hypothesis that chronic 17Beta‐estradiol (E2) supplementation would reduce BP and alter the renal expression of the nuclear estrogen receptors, alpha (ER‐alpha) and beta (ER‐beta). Placebo or E2 pellets (1.5 mg 17Beta‐estradiol, 60‐day release) were initiated at 12 months of age for 6 weeks followed by measurement of BP in conscious, chronically catheterized animals and collection of kidneys for molecular analysis. Real‐time PCR was used to measure renal mRNA expression of ER‐alpha and ER‐beta; Western blot was used to measure ER‐Alpha protein expression. BP was significantly decreased in E2‐treated IUGR relative to placebo‐treated IUGR (decrease of 13 mmHg, P<0.05), whereas BP was not significantly altered in E2‐treated control relative to placebo‐treated control (increase of 2 mmHg). Preliminary studies suggest that cortical ER‐alpha mRNA expression did not differ in placebo‐treated IUGR versus placebo‐treated control. Yet, medullary ER‐alpha mRNA expression was decreased in placebo‐treated IUGR versus placebo‐treated control, but not in E2‐treated IUGR. Preliminary studies also reveal that cortical ER‐beta mRNA expression was increased 4‐fold in placebo‐treated IUGR versus placebo‐treated control. However, cortical ER‐beta mRNA expression was not increased in E2‐treated IUGR counterparts. Cortical and medullary ER‐alpha protein expression did not differ in IUGR versus control, or E2‐treated versus placebo‐treated groups. The CV protective effects attributed to estrogen include: vasodilation via nitric oxide production, angiogenesis, and modulation of components of the renin angiotensin system (RAS). Therefore, alterations in BP in female IUGR vs. female control may be attributed to changes in the expression of ERs with future studies investigating the effect of E2 on the RAS which is up‐regulated in female IUGR at 12 months of age. To conclude, although a loss of female sex hormones may not be the only contributing factor to increases in BP after menopause in LBW women, therapies that target specific estrogen receptors may prove beneficial in improving cardiovascular health.Support or Funding InformationHL074927, AHAGRNT19900004 (Alexander), HL51971, P20GM104357 (Hall), T32HL105324 (Granger), F30DK112718 (Newsome)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.