دورية أكاديمية
Biological sex modifies aldosterone's secretion at a cellular level.
| العنوان: | Biological sex modifies aldosterone's secretion at a cellular level. |
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| المؤلفون: | Gholami SK; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Tay CS; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur, Malaysia., Lee JM; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur, Malaysia., Zagoren E; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Maris SA; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Department of Exercise Science and Athletic Training, Springfield College, Springfield, Massachusetts, USA., Wong JY; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur, Malaysia., Garza AE; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Caliskan Guzelce E; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Pojoga LH; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Adler GK; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Romero JR; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Williams GH; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. |
| المصدر: | The Journal of endocrinology [J Endocrinol] 2021 Nov 24; Vol. 252 (1), pp. 1-13. Date of Electronic Publication: 2021 Nov 24. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioScientifica Country of Publication: England NLM ID: 0375363 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-6805 (Electronic) Linking ISSN: 00220795 NLM ISO Abbreviation: J Endocrinol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Jan. 2011- : Bristol, UK : BioScientifica Original Publication: Bristol, UK : Society for Endocrinology |
| مواضيع طبية MeSH: | Sex Characteristics*, Aldosterone/*metabolism , Zona Glomerulosa/*metabolism, Angiotensin II/pharmacology ; Animals ; Cells, Cultured ; Female ; Gene Expression/drug effects ; Male ; Rats ; Rats, Wistar ; Secretory Pathway/drug effects ; Secretory Pathway/genetics ; Secretory Pathway/physiology ; Zona Glomerulosa/cytology ; Zona Glomerulosa/drug effects |
| مستخلص: | Inconsistencies have been reported on the effect of sex on aldosterone (ALDO) levels leading to clinical confusion. The reasons for these inconsistencies are uncertain but include estrogen and/or its receptor modulating target gene responses to mineralocorticoid receptor activation and ALDO secretagogues' levels. This study's goal was to determine whether ALDO's biosynthesis also differed by sex. Two approaches were used. First, plasma renin activity and aldosterone were measured in rats. Both were significantly higher in males. Secondly, using rat zona glomerulosa (ZG) cells, we assessed three ex vivo areas: (1) activity/levels of early steps in ALDO's biosynthesis (StAR and CYP11A1); (2) activity/levels of a late step (CYP11B2); and (3) the status of the mineralocorticoid receptor (MR)-mediated, ultrashort feedback loop. Females had higher expression of CYP11A1 and StAR and increased CYP11A1 activity (increased pregnenolone/corticosterone levels) but did not differ in CYP11B2 expression or activity (ALDO levels). Activating the ZG's MR (thereby activating the ultrashort feedback loop) reduced CYP11B2's activity similarly in both sexes. Exvivo, these molecular effects were accompanied, in females, by lower ALDO basally but higher ALDO with angiotensin II stimulation. In conclusion, we documented that not only was there a sex-mediated difference in the activity of ALDO's biosynthesis but also these differences at the molecular level help explain the variable reports on ALDO's circulating levels. Basally, both in vivo and ex vivo, males had higher ALDO levels, likely secondary to higher ALDO secretagogue levels. However, in response to acute stimulation, ALDO levels are higher in females because of the greater levels and/or activity of their StAR/CYP11A1. |
| معلومات مُعتمدة: | R01 HL104032 United States HL NHLBI NIH HHS; R01 HL136567 United States HL NHLBI NIH HHS; R01 HL096518 United States HL NHLBI NIH HHS; T32 HL007609 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: CYP11A1; CYP11B2; StAR; Zonal Glomerulosa; aldosterone biosynthesis; corticosterone; pregnenolone; sex |
| المشرفين على المادة: | 11128-99-7 (Angiotensin II) 4964P6T9RB (Aldosterone) |
| تواريخ الأحداث: | Date Created: 20211013 Date Completed: 20211228 Latest Revision: 20211228 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1530/JOE-21-0126 |
| PMID: | 34643545 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1479-6805 |
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| DOI: | 10.1530/JOE-21-0126 |