Introduction: Early pre-pubertal exposure to androgens induces an increase in blood pressure (BP) and renal injury in females, as seen in polycystic ovary syndrome females. However, it is not clear whether treatment with gender-affirming hormonal therapy (GAHT) in trans-men have an impact on their BP and renal health as adults and with aging. Therefore, the present study was undertaken to test the hypothesis that chronic androgen supplements (starting post-pubertal, model of GAHT) in female-to-male trans-sex rats will increase BP and promote renal injury that are exaggerated with aging. Methods: Female SD rats were implanted with testosterone propionate-filled silastic implants (TP, 7.5 mg/10 mm silastic tube/rat, replaced every 3 wks) starting at 7 wks of age (post-pubertal) until 17 months (mos) of age and compared to controls (CON, empty silastic implants). Serum testosterone was measured by LC/MS at 3 mos of age (n=4/grp). Radiotelemetry transmitters were implanted and mean arterial pressure (MAP) was measured at 3 and 17 mos of age (n=3-6/grp). Body composition was determined at 3 and 17 mos of age (n=3-4/grp). Proteinuria was determined at 3, 5 and 7 mos of age (n=4/grp). Serum and urinary creatinine (Cr) were measured at 7 mos of age and Cr clearance was calculated (n=4/grp). Urinary kidney injury molecule-1 (Kim-1) was measured at 12 mos of age (n=3-4/grp). Results: TP had significantly higher serum testosterone compared to CON (6.4 ± 1.5 vs 0.2 ± 0.05 ng/ml; p<0.05). Despite the similar fat mass, lean mass was significantly higher in TP compared to CON starting at 3 mos of age (253.9 ± 6.7 vs 217.7 ± 5.8 g; p<0.05), until 17 mos of age (325.7 ± 15.1 vs 253.5 ± 3.9 g; p<0.05). Proteinuria was significantly higher in TP compared to CON at 5 and 7 mos of age (7.6 ± 1.1 vs 2.4 ± 0.5 mg/24 h and 10.1 ± 1.6 vs 2.4 ± 0.4 mg/24 h, respectively, p<0.05). Cr clearance was significantly lower (0.24 ± 0.03 vs 0.32 ± 0.02 ml/min/100 g, p<0.05) and urinary Kim-1 was significantly higher (6.3 ± 1.5 vs 3.5 ± 0.2 ng/24 h, p<0.05) in TP compared to CON. Importantly, MAP was significantly higher in TP compared to CON starting at 3 mos of age (112 ± 3 vs 106 ± 4 mmHg, p<0.05), with further increases at 17 mos of age (133 ± 1 vs 117 ± 6 mmHg, p<0.05). Conclusion: Post-pubertal testosterone in female sex promotes renal injury and increases BP, independent of adiposity. Aging promotes further increases in BP, suggesting increased risk of cardiovascular diseases. Future studies should determine the mechanisms behind the increase in BP in the female-to-male trans-sex model. P20GM121334, AHA Career Development Award 938320, P20GM104357, R01HL135089, P01HL051971 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Background: Polycystic ovary syndrome ( PCOS ) is the most common endocrinopathy affecting women of reproductive age. It is characterized by hyperandrogenemia, increased blood pressure ( BP ) and metabolic dysfunction. Consumption of western diet ( WD ) aggravates the reproductive and metabolic phenotypes of PCOS. Yet, the effect of WD consumption on BP in PCOS women is not clear. Therefore, this study was undertaken to test the hypothesis that WD consumption in hyperandrogenemic female ( HAF ) rats (a model that mimics most of PCOS symptoms) increases BP along with increasing renal expression of the vasoconstrictor ( VC ) components of the renin-angiotensin system ( RAS ). Methods: At 4 wks of age, female Sprague Dawley rats were implanted (s.c.) with either 5α-dihydrotestosterone pellets (7.5 mg/90 d; HAF rats) or placebo pellets (controls; CON) , that were replaced throughout life. At 4 wks of age, HAF and CON rats were also started on WD (high fat and high sucrose content) or control diet ( CD ), thus forming 4 groups; CON-CD, CON-WD, HAF-CD and HAF-WD. At 20 wks of age, rats were implanted with radiotelemetry transmitters in the abdominal aorta to measure mean arterial pressure ( MAP ) [n=4-5/group]. Another set of rats (n=3-6/group) were euthanized and kidneys collected for measurement of components of the RAS by western blot. Results: are shown in Table 1 . Conclusion: WD consumption in HAF results in further increases in BP, despite upregulation of components of the intrarenal vasodilator RAS (ACE2 and AT2R), which is likely a protective mechanism. Future studies will determine the role(s) of other major VC pathways (e.g. endothelin system) in hypertension in WD-fed HAFs.
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