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J Endocrinol Invest. 2016 Oct;39(10):1149-58. doi: 10.1007/s40618-016-0494-9. Epub 2016 Jun 16.

The anti-estrogenic activity of indole-3-carbinol in neonatal rat osteoblasts is associated with the estrogen receptor antagonist 2-hydroxyestradiol.

Author information

1
Department of Reproductive Biology, "Carlos Gual Castro", Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Vasco de Quiroga 15, Sección XVI, 14000, Mexico City, Mexico. juanaenriquez@yahoo.com.mx.
2
Genomics of Bone Metabolism Laboratory, Instituto Nacional de Medicina Genómica, 14610, Mexico City, Mexico.
3
Research Support Network, INCMNSZ-Universidad Nacional Autónoma de México, 14000, Mexico City, Mexico.
4
Department of Reproductive Biology, "Carlos Gual Castro", Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Vasco de Quiroga 15, Sección XVI, 14000, Mexico City, Mexico.

Abstract

PURPOSE:

To gain new insight into the roles of cruciferous vegetable-derived bioactive phytochemicals in bone cells, we investigated the effects of indole-3-carbinol (I3C) on cell proliferation and differentiation in estradiol (E2)-exposed calvarial osteoblasts that were obtained from neonatal rats.

METHODS:

Osteoblast activity was assessed by analyzing cellular DNA, cell-associated osteocalcin (OC) levels and alkaline phosphatase (AP) activity. We also examined [(3)H]-estrone (E1) metabolism and estrogen-agonistic and estrogen-antagonistic activities of 2-hydroxy (OH) E1 and 2-OHE2 and their capacity to displace [(3)H]-E2 at ER binding sites using competition studies.

RESULTS:

I3C did not affect on cellular DNA, OC levels or AP activity. However, I3C completely inhibited E2-induced increases in cell proliferation and differentiation in neonatal rat osteoblasts. Metabolic studies demonstrated that I3C promoted the conversion of [(3)H]-E1 to 2-OHE1 and 2-OHE2 and those higher rates of conversion (twofold-threefold) were archived when a higher dose of I3C was applied. Proliferation and differentiation studies showed that 2-OHE2 but not 2-OHE1 inhibited E2-induced increases in cell proliferation and differentiation via an ER-mediated mechanism. Likewise, Esr1 was expressed at high level than Esr2. 2-OHE1 showed no activity or affinity for ER.

CONCLUSIONS:

This study is the first to show that a bioactive compound derived from cruciferous vegetables, I3C, abolishes the E2-mediated stimulation of cell activities including, proliferation and differentiation, in rat osteoblasts and increases the 2-hydroxylation of E1, resulting in the formation of inactive and anti-estrogenic metabolites. These results suggest that in neonatal rat osteoblasts, the anti-estrogenic effect of I3C is mediated by 2-OHE2 through ER-α.

KEYWORDS:

Estrogen metabolites; Indole-3-carbinol; Osteoblast 2-hydroxylation; Osteoblasts differentiation; Osteoblasts proliferation

PMID:
27312859
DOI:
10.1007/s40618-016-0494-9
[Indexed for MEDLINE]

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