The human kidney is a progesterone-metabolizing and androgen-producing organ
Abstract
Progesterone (P) is a potent antagonist of the human mineralocorticoid receptor (MR) in vitro. We have previously demonstrated effective downstream metabolism of P in the kidney. This mechanism potentially protects the MR from P action. Here, we have investigated the expression and functional activity of steroidogenic enzymes in human kidney. RT-PCR analysis demonstrated the expression of 5 alpha-reductase type 1, 5 beta-reductase, aldo-keto-reductase (AKR) 1C1, AKR1C2, AKR1C3, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) type 2, and 17 alpha-hydroxylase/17,20-lyase (P450c17). The presence of 3 beta-HSD type 2 and P450c17 indicated that conversion of pregnenolone to dehydroepiandrosterone (DHEA) and to androstenedione may take place effectively in kidney. To investigate this further, we incubated kidney subcellular fractions with radiolabeled pregnenolone. This resulted in efficient formation of DHEA from pregnenolone, indicating both 17 alpha-hydroxylase and 17,20-lyase activities exerted by P450c17. Radiolabeled DHEA was converted via androstenedione, androstenediol, and testosterone, indicating both 3 beta-HSD type 2 activity and 17 beta-HSD activity. In addition, the conversion of testosterone to 5 alpha-dihydrotestosterone was detectable, indicating 5 alpha-reductase activity. In conclusion, we verified the expression and functional activity of several enzymes involved in downstream metabolism of P and androgen synthesis in human kidney. These findings may be critical to the understanding of water balance during the menstrual cycle and pregnancy and of sex differences in hypertension.
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Expression of genes (AKR1D1 and AKR1C2) encoding enzymes contributing to phase 1 metabolism and inactivation of androgens has been demonstrated in the kidney.
“Additionally, the expression of genes (AKR1D1 and AKR1C2) encoding enzymes contributing to phase 1 metabolism and inactivation of androgens have been demonstrated (Quinkler et al., 2003).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Quinkler et al., 2003
The kidney has been shown to be able to catalyse the biosynthesis of active androgens using PREG as precursor for DHEA production by CYP17A1.
“Surprisingly the kidney has been shown to be able to catalyse the biosynthesis of active androgens using PREG as precursor for DHEA production by CYP17A1 (Quinkler et al., 2003).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Quinkler et al., 2003
The relevance of the kidney androgen biosynthesis results to the healthy kidney is questionable because the tissue used was derived from tumour nephrectomies.
“It should, however, be noted that the tissue used in this study was derived from tumour nephrectomies, thus bringing into question the relevance of these results to the healthy kidney.”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Quinkler et al., 2003
DHEA could be further metabolised to T, via A4 or 5α-dione, and the resulting T could be 5α-reduced to DHT in the kidney.
“DHEA could be further metabolised to T, via A4 or 5α-dione, and the resulting T could be 5α-reduced to DHT.”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Quinkler et al., 2003
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- Authors
- Quinkler, M., Bumke-Vogt, C., Meyer, B., Bähr, V., Oelkers, W., & Diederich, S.
- Affiliations
- Freie Universität Berlin (DE)
- Corresponding author
- Quinkler, M.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2003-06
- Volume
- 88
- Issue
- 6
- Pages
- 2803-2809
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2005757009
- Cited by
- 87
- References
- 48
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 8 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 8 · 2019: 5 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 1 · 2012: 5
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- progesterone metabolism, androgen production, human kidney, steroidogenic enzymes, 17α-hydroxylase/17,20-lyase, P450c17, 5α-reductase, pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, mineralocorticoid receptor, water balance, menstrual cycle, pregnancy, sex differences in hypertension
- MeSH terms
- Androgens, Dehydroepiandrosterone, Humans, Kidney, Pregnenolone, Progesterone, Subcellular Fractions
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