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Role of Sex Hormones in Prevalent Kidney Diseases.

ABSTRACT: Chronic kidney disease (CKD) is a constantly growing global health burden, with more than 840 million people affected worldwide. CKD presents sex disparities in the pathophysiology of the disease, as well as in the epidemiology, clinical manifestations, and disease progression. Overall, while CKD is more frequent in females, males have a higher risk to progress to end-stage kidney disease. In recent years, numerous studies have highlighted the role of sex hormones in the health and diseases of several organs, including the kidney. In this review, we present a clinical overview of the sex-differences in CKD and a selection of prominent kidney diseases causing CKD: lupus nephritis, diabetic kidney disease, IgA nephropathy, and autosomal dominant polycystic kidney disease. We report clinical and experimental findings on the role of sex hormones in the development of the disease and its progression to end-stage kidney disease.

SUBMITTER: Conte C

PROVIDER: S-EPMC10179191 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Role of Sex Hormones in Prevalent Kidney Diseases.

Conte Carolina C Antonelli Giulia G Melica Maria Elena ME Tarocchi Mirko M Romagnani Paola P Peired Anna Julie AJ

International journal of molecular sciences 20230504 9

Chronic kidney disease (CKD) is a constantly growing global health burden, with more than 840 million people affected worldwide. CKD presents sex disparities in the pathophysiology of the disease, as well as in the epidemiology, clinical manifestations, and disease progression. Overall, while CKD is more frequent in females, males have a higher risk to progress to end-stage kidney disease. In recent years, numerous studies have highlighted the role of sex hormones in the health and diseases of s ...[more]

PMID: 37175947

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Project description:BackgroundA growing body of evidence highlights sex differences in the diagnostic accuracy of cardiovascular imaging modalities. Nonetheless, the role of sex hormones in modulating myocardial perfusion and coronary flow reserve (CFR) is currently unclear. The aim of our study was to assess the impact of female and male sex hormones on myocardial perfusion and CFR.MethodsRest and stress myocardial perfusion imaging (MPI) was conducted by small animal positron emission tomography (PET) with [18F]flurpiridaz in a total of 56 mice (7-8 months old) including gonadectomized (Gx) and sham-operated males and females, respectively. Myocardial [18F]flurpiridaz uptake (% injected dose per mL, % ID/mL) was used as a surrogate for myocardial perfusion at rest and following intravenous regadenoson injection, as previously reported. Apparent coronary flow reserve (CFRApp) was calculated as the ratio of stress and rest myocardial perfusion. Left ventricular (LV) morphology and function were assessed by cardiac magnetic resonance (CMR) imaging.ResultsOrchiectomy resulted in a significant decrease of resting myocardial perfusion (Gx vs. sham, 19.4 ± 1.0 vs. 22.2 ± 0.7 % ID/mL, p = 0.034), while myocardial perfusion at stress remained unchanged (Gx vs. sham, 27.5 ± 1.2 vs. 27.3 ± 1.2 % ID/mL, p = 0.896). Accordingly, CFRApp was substantially higher in orchiectomized males (Gx vs. sham, 1.43 ± 0.04 vs. 1.23 ± 0.05, p = 0.004), and low serum testosterone levels were linked to a blunted resting myocardial perfusion (r = 0.438, p = 0.020) as well as an enhanced CFRApp (r = -0.500, p = 0.007). In contrast, oophorectomy did not affect myocardial perfusion in females. Of note, orchiectomized males showed a reduced LV mass, stroke volume, and left ventricular ejection fraction (LVEF) on CMR, while no such effects were observed in oophorectomized females.ConclusionOur experimental data in mice indicate that sex differences in myocardial perfusion are primarily driven by testosterone. Given the diagnostic importance of PET-MPI in clinical routine, further studies are warranted to determine whether testosterone levels affect the interpretation of myocardial perfusion findings in patients.

Project description:BackgroundOur previous study revealed that adult female rats respond differently to trauma than adult males, recapitulating sex differences in symptoms of post-traumatic stress disorder (PTSD) exhibited by women and men. Here, we asked two questions: does the female phenotype depend on (1) social housing condition and/or (2) circulating gonadal hormones?MethodsFor the first study, the effects of single prolonged stress (SPS) were compared for females singly or pair-housed. For the second study, adult male and female rats were gonadectomized or sham-gonadectomized 2 weeks prior to exposure to SPS, with half the gonadectomized rats given testosterone. In addition to the typical measures of the trauma response in rats, acoustic startle response (ASR), and the dexamethasone suppression test (DST), we also used two other measures typically used to assess depressive-like responses, social interaction and sucrose preference. Glucocorticoid receptor (GR) expression in the hypothalamus was also examined.ResultsWe now report that the distinct trauma response of female rats is not influenced by social housing condition. Moreover, sex differences in the response to SPS based on ASR and DST, replicated in the current study, are independent of adult gonadal hormones. Regardless of hormonal status, traumatized males show a hyper-responsive phenotype whereas traumatized females do not. Moreover, testosterone treatment in adulthood did not masculinize the response to trauma in females. Notably, both sucrose preference and social interaction tests revealed an effect of trauma in females but not in males, with the effects of SPS on sucrose preference dependent on ovarian hormones. Effects of SPS on GR expression in the hypothalamus also depended on gonadal hormones in females.ConclusionsWe propose that the trauma response for female rats is depressive in nature, recapitulating the female bias in PTSD for internalizing symptoms and major depression in contrast to the externalizing symptoms of males. Presumed core markers of PTSD (enhanced ASR and negative feedback control of corticosterone) are apparently relevant only to males and are independent of adult gonadal hormones. Such sex differences in trauma responding are likely determined earlier in life. We conclude that males and females show fundamentally different responses to trauma that do not simply reflect differences in resilience.

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Role of Sex Hormones in Prevalent Kidney Diseases.

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Role of Sex Hormones in Prevalent Kidney Diseases.

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