An innovative LC-MS/MS-based method for determining CYP 17 and CYP 19 activity in the adipose tissue of pre- and postmenopausal and ovariectomized women using 13C-labeled steroid substrates
Abstract
CONTEXT: Does adipose tissue produce steroid hormones like an endocrine organ? OBJECT: To clarify whether adipose tissue produces sex steroid hormone like an endocrine organ, we estimated several key steroid hormone levels, as well as CYP17 and CYP19 activity, in ovariectomized, pre- and postmenopausal women by liquid chromatography-tandem mass spectrometry (LC-MS/MS). SUBJECTS AND METHODS: The subjects were 19 premenopausal (n = 12), postmenopausal (n = 4), and ovariectomized women (n = 3) aged 27-68 years. Serum, visceral adipose and sc adipose samples were taken from these subjects and stored at -70°C. The levels of cortisol, cortisone, progesterone (Prog), androstenedione, dehydroepiandrosterone, estrone, estradiol (E2), and T in serum and adipose tissue were estimated simultaneously by LC-MS/MS. CYP17 and CYP19 activity in tissues were assayed with the use of (13)C-labeled steroid precursors and LC-MS/MS-based estimation of the metabolites. RESULTS: E2 and Prog levels in the sera of postmenopausal or ovariectomized women were less than 10% of those in premenopausal women. No marked variations were seen in other hormones. Estrone, androstenedione, dehydroepiandrosterone, and Prog levels in the visceral and sc tissues of postmenopausal and ovariectomized women were 9-60 times higher than those in serum, whereas E2 and T levels were 3- to 7-fold higher than those in serum, and cortisol and cortisone levels were 20% of those found for serum. CYP17 in adipose tissue was found to have 17-hydroxylase and 20,17-lyase activity, with each catalytic activity being essentially equal. Therefore, CYP17 in adipose tissue is of the testicular/ovarian type but not adrenal type, which has 17-hydroxylase activity dominant. The presence of CYP19 activity in adipose tissue was approximately 3% of CYP17. CONCLUSION: Our findings suggest that adipose tissue acts as an endocrine organ, with CYP17 and CYP19 activity playing an essential role in sex steroid hormone biosynthesis.
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In postmenopausal women, tissue to serum ratios of estrone (E1) and especially estradiol (E2) tend to be higher when compared to premenopausal women.
“In postmenopausal women, tissue to serum ratios of E 1 and especially E 2 tend to be higher when compared to premenopausal women [12,20,21].”
From Adipose tissue estrogen production and metabolism in premenopausal women (2021) · cites this paper as [20]
The ‘Hormone levels in adipose tissue’ section (page not available) reports higher tissue-to-serum E2 ratios in postmenopausal women (3.0–4.3) than in premenopausal women (1.5–1.6). It reports that E1 levels in adipose tissue exceed serum levels in both groups, but does not establish that the E1 ratio is higher after menopause. (LLM, conf=0.85)
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References 33 · Cited by 33
Research works printed but not linked: 1
- Sharp L, Cardy AH, Cotton SC, Little J. CYP17 gene polymor- phisms: prevalence and associations with hormone levels and related factors. Am J Epidemiol. 2004;160:729 -740.
- Authors
- Kinoshita, T., Honma, S., Shibata, Y., Yamashita, K., Watanabe, Y., Maekubo, H., Okuyama, M., Takashima, A., & Takeshita, N.
- Affiliations
- Toho University Medical Center Sakura Hospital (JP)
- ASKA Pharmaceutical (Japan) (JP)
- Gunma University (JP)
- Tohoku Medical and Pharmaceutical University (JP)
- Corresponding author
- Kinoshita, Toshihiko
- Shibata, Yasuhiro
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2014-04-01
- Volume
- 99
- Issue
- 4
- Pages
- 1339-1347
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2170074392
- Cited by
- 33
- References
- 33
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 8 · 2014: 2
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- aromatase, adipose tissue, steroidogenesis, menopause, ovariectomy, visceral adipose tissue, subcutaneous adipose tissue, estradiol, progesterone
- MeSH terms
- Adipose Tissue, Adult, Aged, Aromatase, Carbon Isotopes, Chromatography, Liquid, Female, Humans, Middle Aged, Ovariectomy, Steroid 17-alpha-Hydroxylase, Premenopause, Postmenopause, Tandem Mass Spectrometry
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