DOCA Reduces Renal Progesterone in Female Rats Independent of Body Weight and Estrogens

Hypertension is the leading modifiable risk factor for heart disease, which remains the primary cause of death in the United States. T cells are known to be critical in the development of hypertension. Effector T cells promote, whereas regulatory T cells (Tregs) attenuate increases in BP. We have previously shown that female hypertensive rats (spontaneously hypertensive rats, angiotensin II, norepinephrine) exhibit a compensatory increase in Tregs with the development of hypertension. However, deoxycorticosterone acetate (DOCA)-salt–treated female Sprague Dawley (SD) rats exhibit a significant reduction in renal Tregs compared with uni-nephrectomized (UNX) females, although Treg levels remain higher than in DOCA-treated UNX males. Females rely on Tregs for BP control; however, it is unclear why Tregs decline in females following DOCA treatment. Sex hormones influence Treg levels, therefore the goal of the current study was to determine the impact of DOCA-salt on renal sex hormone levels in female rats. We hypothesized that female sex hormone levels would decrease with DOCA-salt treatment. 10-week-old female SD rats were UNX and allowed to recover for 2 weeks before being randomized DOCA-salt (200 mg, s.c.) with 0.9% saline water or tap water control (n=5/group). All rats were euthanized after 3 weeks. Body weights were recorded. Kidneys and the uterus were collected and weighed. Kidneys were snap-frozen for measurement of sex hormones by mass spectrometry. Data were compared via Student T-test. There was no difference in body weight between DOCA-treated rats and UNX controls (g: 220±6 vs 236±7, P=0.12). Interestingly, the uterine to body weight ratio was lower in DOCA vs. control females (0.002±.0001 vs 0.001±0.0002, P=0.04). As expected, DOCA-treated rats had greater kidney weight to body weight ratio (g: vs 0.008±0.0003 vs 0.004±0.0002, P< 0.0001) and renal deoxycorticosterone levels compared to UNX controls (ng/g: 35±6 vs 5±2, P=0.001). There were no differences in renal estrone (ng/g:19±9 vs 10±2, P=0.36) or estradiol (ng/g:15±4 vs 16±4, P=0.89) in female DOCA-treated vs. UNX control rats. However, DOCA-treated rats had significantly lower renal progesterone levels compared to UNX females (ng/g:26±5 vs 10±4, P=0.05, student T test). In conclusion, DOCA-treated females had lower renal progesterone levels compared to UNX females independent of body weight, estrone, and estradiol. Since progesterone has been shown to promote the development of regulatory T cells, future studies will determine whether reduced Tregs are mediated by reduced renal progesterone levels in female DOCA-treated rats. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.