Estrone sulfate Is a Major source of local estrogen formation in human bone
Abstract
Estrone sulfate (E1S) is the most abundant estrogen in the circulation of adults. The present study was undertaken to assess estrone (E1) and estradiol formation from E1S in freshly resected bone [bone fragments (BFs)] and osteoblast-like cells (hOB) cultured from BFs. Furthermore, we compared estrogen formation from E1S in rat and human osteosarcoma (OS) cell lines and that of estrogen formation from E1S with that of aromatization of androstenedione and testosterone in BFs and those from E1S and androstenedione in hOB cells. The bone used was from the head of the femur from a total of 15 women and 12 men. Steroid sulfatase activity (STA) was found, and the formation of estrone and estradiol from E1S was demonstrated. STA was similar in cells derived from BFs of men and women. STA was significantly lower in OS cell lines, compared with hOB cells. Estrogen formation from E1S in BFs was at least 20 times higher than that from androstenedione and about 50 times higher than that from testosterone. Similarly, estrogen formation from E1S in hOB cells exceeded the values derived from aromatization of androstenedione by two orders of magnitude. Based on these results, we conclude that hOB cells express the same pattern of E1S metabolism as resected bone and thus may accurately mirror the in vivo situation in man. In comparison with hOB cells, STA is fundamentally lower in widely used OS cell lines that express an osteoblastic phenotype. This shortcoming precludes their use as model cell lines to unravel STA metabolic pathways and its regulation in nontumorous bone. E1S is a major source of local bioactive estrogen formation in human bone. Because bone is highly susceptible to estrogen action, local estrogen formation from E1S may play an important role in bone maturation and homeostasis, particularly in elderly adults.
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Estrone sulfate is the predominant estrogen in circulation for both men and premenopausal women and serves as a biologically inactive reservoir for the generation of active estrogens in target tissues.
“Notably, estrone sulfate is the predominant estrogen in circulation for both men and premenopausal women and serves as a biologically inactive reservoir for the generation of active estrogens in target tissues [40,309,310].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [309]
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“biologically inactive reservoir for the generation of active estrogens in target tissues [40,309,310].”
- Authors
- Muir, M., Romalo, G., Wolf, L., Elger, W., & Schweikert, H.-U.
- Affiliations
- University of Bonn (DE)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2004-09
- Volume
- 89
- Issue
- 9
- Pages
- 4685-4692
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2147842882
- Cited by
- 41
- References
- 34
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 1
- FWCI
- 1.25
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Keywords
- estrone sulfate, steroid sulfatase, estrone, estradiol, osteoblast-like cells, osteosarcoma cell lines, androstenedione aromatization, testosterone aromatization, bone, bone homeostasis, skeletal maturation, sex differences
- MeSH terms
- Adult, Aged, Aged, 80 and over, Animals, Bone and Bones, Estrogens, Estrone, Female, Humans, Male, Middle Aged, Osteoblasts, Osteosarcoma, Cell Line, Tumor, Rats
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