Summary
In order to investigate the possible role of estrogen in the development of cartilage and bone we studied by immunofluorescence immunohistochemistry and autoradiography 26 human embryos and fetuses 7–22 weeks in gestational age associated with pregnancy interrupted for nonmedical reasons. In order to demonstrate the presence of estrogen receptors (ERs) in human fetal cartilage, cryostat sections of long bones and lumbar and thoracic vertebrae were prepared for (1) fluorescent immunocytochemistry using an antiidiotypic monoclonal antibody to antiestradiol receptor monoclonal Ab labeled with fluorescein isothiocyanate (FITC), (2) immunohistochemistry using monoclonal antihuman estradiol receptor antibody, labeled with strept. A-B immunoperoxidose, and (3) autoradiographic localization of estradiol using labeled (3 H) l7β estradiol. In fetuses aged 10 weeks or older, intranuclear and perinuclear localization of ER was demonstrated by all methods, mainly amongst chondrocytes of the proliferating and higher hypertrophic zones of the epiphyses and in the cartilage of vertebral bodies. These data suggest that estrogen acts directly on chondrocytes of human fetuses through an ER-mediated mechanism.
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References
Lebovitz HE, Eisenbarth GS (1975) Hormonal regulation of cartilage growth and metabolism. Vitam Horm 33:575–648
Thomsen K, Riis B, Christiansen C (1986) Effect of estrogen/ gestagen and 24R,25-dihydroxyvitamin D3 therapy on bone formation in postmenopausal women. J Bone Miner Res 1:503–507
Notelovitz M (1989) Estrogen replacement therapy: Indications, contraindications and agent selection. Am J Obst Gynec 161:1832–1842
Eriksen EF, Colvard DS, Berg WJ, Grahm MG, Spelsberg TC, Riggs BL (1988) Evidence to estrogen receptors in normal human osteoblast like cells. Science 241:84–86
Komm BS, Terpening CM, Benz DG, Graeme KA, Gallegos A, Korc M, Greene GL, O'Malley BM, Haussler MR (1988) Estrogen binding, receptor mRNA and biological response in osteoblast like osteosarcoma cells. Science 241:81–83
Dayani N, Corvol MT, Robel P, Eychenne B, Moncharmont B, Tsagris L, Rappaport R (1988) Estrogen receptors in cultured rabbit articular chondrocytes. Influence of age. J Steroid Biochem 31:351–356
Pinus H, Yaffe P, Ornoy A (1991) Evidence for direct estradiol binding to cartilage of female and male young mice and rats. Abstracts of the 15th International Congress of Biochemistry, Jerusalem, Israel. Aug 4–8, p 73
Mor G, Amir-Zaltsman Y, Barnard G, Kohen F (1992) Characterization of the anti-idiotypic antibody mimicking the action of estradiol and its interactions with estrogen receptors. Endocrinology 130:3633–3640
Barnard G, Kohen F (1990) Idiometric assay: Noncompetitive immunoassay for small molecules typified by the measurement of estradiol in serum. Clin Chem 36:1945–1950
Stefanini M, De Martino C, Zamboni L (1967) Fixation of ejaculated spermatozoa for electron microscopy. Nature 216:173–174
Sternberger LA (1979) Immunocytochemistry. John Wiley, New York
Hsu SM, Raine L, Fanger H (1981) Comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol 75:734–738
Burnett CL, Reddi AH (1983) Influence of estrogen and progesterone on matrix induced endochondral bone formation. Calcif Tissue Int 31:609–614
Colvard DS, Eriksen EF, Keeting PE, Wilson EM, Lubahn DB, French FS, Riggs BL (1989) Identification of androgen receptors in normal human osteoblastic like cells. Proc Natl Acad Sci USA 86:854–857
King WJ, Green GL (1984) Monoclonal antibodies localize estrogen receptor in the nuclei of target cells. Nature 307:745–747
Perrot-Depplaret M, Groyer-Picard MT, Garcia E, Lorenzo F, Milgram E (1988) Immunocytochemical demonstration of estrogen and progesterone receptors in muscle cells of uterine arteries in rabbits and humans. Endocrinology 123:1511–1519
Welshons VW, Lieberman ME, Gorske J (1984) Nuclear localization of monoclonal estrogen receptor. Nature 307:747–749
Raisz LG, Kream BE (1983) Regulation of bone formation. N Engl J Med 309:83–89
Ornoy A (1973) Transplacental effects of estrogens on osteogenesis in rat fetuses. Pathology 5:183–188
Schwartz Z, Neubauer T, Goldstein M, Adi S, Soskolne WA, Ornoy A (1991). Direct and sex specific enhancement of bone formation and calcification by sex steroids in vitro (biochemical and morphometric study) Endocrinology 129:1167–1174
Takahashi NN, Noumura T (1987) Sexually dimorphic and laterally assymetric development of the embryonic Duck syrinx: effects of estrogen on in-vitro cell proliferation and chondrogenesis. Dev Biol 21:417–422
Blanchard O, Tsagris L, Rappaport R, Duval-Beaupere G, Corvol M (1991) Age dependent responsiveness of rabbit and human cartilage cells to sex steroids in vitro. J Steroid Biochem Mol Biol 40:711–716
Nasatzky E, Schwartz Z, Soskolne WA, Boyan B, Suvain L, Ornoy A (1993) Sex dependent effects of l7β estradiol on chondrocyte differentiation in culture. Am J Cell Physiol (in press)
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Ben-Hur, H., Mor, G., Blickstein, I. et al. Localization of estrogen receptors in long bones and vertebrae of human fetuses. Calcif Tissue Int 53, 91–96 (1993). https://doi.org/10.1007/BF01321885
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DOI: https://doi.org/10.1007/BF01321885