Background: 17α-hydroxylase deficiency is a rare autosomal recessive disorder caused by mutations in the cytochrome P450 family 17 subfamily A member 1 gene. The major clinical presentation includes hypertension, hypokalemia, male pseudohermaphroditism and female gonadal dysplasia. Hundreds of pathogenic variants have been reported in this disorder, and some common mutations were found to be race-specific. Case presentation: In this study, we reported 5 Chinese girls with 17α-hydroxylase deficiency from Henan Province. The patients all came to the hospital for hypertension, and they also presented with sexual infantilism. The average age of the patients was 14 years old, ranging from 12 to 17 years old. They all had reduced blood cortisol, estradiol (E2), and testosterone (TESTO) and increased adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). They all had the appearance of females; however, three of the chromosome karyotypes were 46XX, and two were 46XY. Conclusions: All of the patients carried a mutation on the 329 amino acid of CYP17A1 exon 6. By summarizing the currently known pathogenic mutations of 17α-hydroxylase deficiency, we demonstrated the prevalence of these gene mutations in Chinese Han and non-Chinese populations.

Renal luminal sodium transport is essential for physiological blood pressure control, and abnormalities in this process are strongly implicated in the pathogenesis of essential hypertension. Renal G protein-coupled receptors (GPCRs) are critical for the regulation of the reabsorption of essential nutrients, ions, and water from the glomerular filtrate. Recently, we showed that GPCR 37L1 (GPR37L1) is expressed on the apical membrane of renal proximal tubules (RPT) and regulates luminal sodium transport and blood pressure by modulating the function of the sodium proton exchanger 3 (NHE3). However, little is known about GPR37L1 intracellular signaling. Here, we show that GPR37L1 is localized to the nuclear membrane, in addition to the plasma membrane in human RPT cells. Furthermore, GPR37L1 signals via the PI3K/AKT/mTOR pathway to decrease the expression of DNA (cytosine-5)-methyltransferase 1 (DNMT1) and enhance NHE3 transcription. Overall, we demonstrate the direct role of a nuclear membrane GPCR in the regulation of renal sodium through epigenetic gene regulation.

Gastrin, secreted by G-cells, and glucagon-like peptide-1 (GLP-1), secreted by L-cells, may participate in the regulation of sodium balance. We studied the effect of sodium in mice in vivo and mouse ileum and human L-cells, on GLP-1 secretion, and the role of NFAT5 and gastrin-releasing peptide receptor (GRPR) in this process. A high-sodium diet increases serum GLP-1 levels in mice. Increasing sodium concentration stimulates GLP-1 secretion from mouse ileum and L-cells. GRP enhances the high sodium-induced increase in GLP-1 secretion. High sodium increases cellular GLP-1 expression, while low and high sodium concentrations increase NFAT5 and GRPR expression. Silencing NFAT5 in L-cells abrogates the stimulatory effect of GRP on the high sodium-induced GLP-1 secretion and protein expression, and the sodium-induced increase in GRPR expression. GLP-1 and gastrin decrease the expression of Na⁺-K⁺/ATPase and increase the phosphorylation of sodium/hydrogen exchanger type 3 (NHE3) in human renal proximal tubule cells (hRPTCs). This study gives a new perspective on the mechanisms of GLP-1 secretion, especially that engendered by ingested sodium, and the ability of GLP-1, with gastrin, to decrease Na⁺-K⁺/ATPase expression and NHE3 function in hRPTCs. These results may contribute to the better utilization of current and future GLP-1-based drugs in the treatment of hypertension.

This study aimed to investigate whether exposure to them increases the risk of hypertension (HTN) and evaluated the mediating role of sex hormones and the modifying effect of lifestyle. This study recruited 560 pairs of HTN cases and matched controls. After applying inclusion and exclusion criteria, 444 pairs were included. Plasma pyrethroid and serum sex hormone levels were measured. Cox regression models were used to assess the association between pyrethroid exposure and HTN risk. Quantile G-computation (QGC), Bayesian Kernel Machine Regression (BKMR),and adaptive elastic-net to (AENET) were employed to evaluate the effects of pyrethroid mixture exposure on HTN. Mediation analyses were performed to examine the role of sex hormones, and interaction analyses were conducted to assess the modifying effect of lifestyle. In model 3, six pyrethroids were positively associated with HTN in males and females (hazard ratio (HR): 1.216-1.930), and pyrethroid mixture exposure was positively associated with HTN in males(HR: 1.513, 95% confidence interval (CI): 1.299-1.762), with fenvalerate identified as the primary contributor. Meanwhile, the increased HTN risk associated with pyrethroid exposure was exacerbated by lower socioeconomic status, current or former smoking, current or former drinking, and a BMI ≥ 24 kg/m². Progesterone exhibited a partial mediating effect on the association between pyrethroid exposure and HTN in males and females, with a mediation proportion of 2.9%-27.6% (P < 0.05). Pyrethroid exposure was associated with an increased risk of HTN. This association was influenced by specific lifestyle and partially mediated by progesterone.