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Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

Gao WL, Wu LS, Zi JH, Wu B, Li YZ, Song YC, Cai DZ - Braz. J. Med. Biol. Res. (2014)

Bottom Line: We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA.Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA.Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedics, Linyi People's Hospital of Shandong Province, Linyi, China.

ABSTRACT
Although 17β-estradiol (E2) deficiency has been linked to the development of osteoarthritis (OA) in middle-aged women, there are few studies relating other estrogens and estrogen metabolites (EMs) to this condition. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA. This method had a precision ranging from 1.1 to 3.1% and a detection limit ranging from 10 to 15 pg. Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA. Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA. In conclusion, our HPLC-ESI-MS/MS method allowed the measurement of multiple biochemical targets in a single assay, and, given its increased cost-effectiveness, simplicity, and speed relative to previous methods, this method is suitable for clinical studies.

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Estrogen metabolism pathways, including estrone, estradiol, and estrogenmetabolites. 17β-HSD: 17beta-hydroxysteroid dehydrogenase; P450 AROM: cytochromeP450 aromatase.
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f01: Estrogen metabolism pathways, including estrone, estradiol, and estrogenmetabolites. 17β-HSD: 17beta-hydroxysteroid dehydrogenase; P450 AROM: cytochromeP450 aromatase.

Mentions: Endogenous estrones (E1) and E2 are synthesized from theandrogenic precursors androstenedione and testosterone, respectively, in a reactioncatalyzed by cytochrome P450 aromatase, which is expressed primarily in ovariangranulosa cells, adipose stromal cells, and the placenta. Circulating E2, theprimary estrogen in premenopausal and early perimenopausal women, declines withmenopause. E1 generated by oxidation of E2 is hydroxylated via twomutually exclusive pathways (6) to generateeither 2-hydroxyestrone (2-OHE1) or 16a-hydroxyestrone (16a-OHE1;Figure 1), which are estrogen agonists (7) with target tissue-specific biological activitiesdistinct from one another and from E2. Compared to E2,16a-OHE1 binds with lower affinity to both the estrogen receptor (8) and to serum sex hormone-binding globulin, and isconsequently more available in estrogen-sensitive target tissues than E2.Although 2-hydroxyestrogens have a reduced binding affinity for the estrogen receptorcompared to 16a-OHE1, they participate in oxidation/reduction reactions(9,10).


Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

Gao WL, Wu LS, Zi JH, Wu B, Li YZ, Song YC, Cai DZ - Braz. J. Med. Biol. Res. (2014)

Estrogen metabolism pathways, including estrone, estradiol, and estrogenmetabolites. 17β-HSD: 17beta-hydroxysteroid dehydrogenase; P450 AROM: cytochromeP450 aromatase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321220&req=5

f01: Estrogen metabolism pathways, including estrone, estradiol, and estrogenmetabolites. 17β-HSD: 17beta-hydroxysteroid dehydrogenase; P450 AROM: cytochromeP450 aromatase.
Mentions: Endogenous estrones (E1) and E2 are synthesized from theandrogenic precursors androstenedione and testosterone, respectively, in a reactioncatalyzed by cytochrome P450 aromatase, which is expressed primarily in ovariangranulosa cells, adipose stromal cells, and the placenta. Circulating E2, theprimary estrogen in premenopausal and early perimenopausal women, declines withmenopause. E1 generated by oxidation of E2 is hydroxylated via twomutually exclusive pathways (6) to generateeither 2-hydroxyestrone (2-OHE1) or 16a-hydroxyestrone (16a-OHE1;Figure 1), which are estrogen agonists (7) with target tissue-specific biological activitiesdistinct from one another and from E2. Compared to E2,16a-OHE1 binds with lower affinity to both the estrogen receptor (8) and to serum sex hormone-binding globulin, and isconsequently more available in estrogen-sensitive target tissues than E2.Although 2-hydroxyestrogens have a reduced binding affinity for the estrogen receptorcompared to 16a-OHE1, they participate in oxidation/reduction reactions(9,10).

Bottom Line: We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA.Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA.Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedics, Linyi People's Hospital of Shandong Province, Linyi, China.

ABSTRACT
Although 17β-estradiol (E2) deficiency has been linked to the development of osteoarthritis (OA) in middle-aged women, there are few studies relating other estrogens and estrogen metabolites (EMs) to this condition. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA. This method had a precision ranging from 1.1 to 3.1% and a detection limit ranging from 10 to 15 pg. Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA. Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA. In conclusion, our HPLC-ESI-MS/MS method allowed the measurement of multiple biochemical targets in a single assay, and, given its increased cost-effectiveness, simplicity, and speed relative to previous methods, this method is suitable for clinical studies.

Show MeSH
Related in: MedlinePlus