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Journal of Clinical Endocrinology & Metabolism, Vol 77, 1014-1019, Copyright © 1993 by Endocrine Society
ARTICLES |
CJ Lockwood, Y Nemerson, G Krikun, V Hausknecht, L Markiewicz, M Alvarez, S Guller and F Schatz
Department of Obstetrics, Gynecology, and Reproductive Sciences, Mount Sinai School of Medicine, New York, New York 10029.
This study examined steroidal regulation of tissue factor expression by cultured endometrial stromal cells. Confluent stromal cell cultures derived from cycling human endometria were exposed to vehicle control, 10(-8) mol/L estradiol (E2), 10(-8)-10(-6) mol/L medroxyprogesterone acetate (MPA), or both E2 and MPA for 2-24 days in serum-containing medium. The progestin enhanced immunoreactive and functionally active stromal cell tissue factor content, achieving peak effects by 8-12 days of culture. Although E2 alone was ineffective, it augmented MPA- enhanced tissue factor content by 8 days of culture, with continued increases beyond 20 days. Dose-dependent effects on tissue factor protein content were observed between 10(-8)-10(-6) mol/L MPA added alone or together with E2. The content of tissue factor mRNA was also increased by MPA and synergistically increased by E2 plus MPA. Similar steroidal effects on stromal cell tissue factor protein and mRNA content were observed using a defined medium. After optimal induction of tissue factor expression by E2 plus MPA, removal of these steroids reduced levels of stromal cell tissue factor mRNA and protein, with virtually complete reversal by day 7 of withdrawal. These time-course and dose-response relationships establish in vitro conditions with which to dissect factors controlling endometrial hemostasis, whereas the observed effects of steroid withdrawal establish a novel model for the study of mechanisms regulating normal and abnormal uterine bleeding.
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C. J. Lockwood, G. Krikun, R. Runic, L. B. Schwartz, A. F. Mesia, and F. Schatz Progestin-Epidermal Growth Factor Regulation of Tissue Factor Expression during Decidualization of Human Endometrial Stromal Cells J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 297 - 301. [Abstract] [Full Text]
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J. J. Brosens, N. Hayashi, and J. O. White Progesterone Receptor Regulates Decidual Prolactin Expression in Differentiating Human Endometrial Stromal Cells Endocrinology, October 1, 1999; 140(10): 4809 - 4820. [Abstract] [Full Text]
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G. Krikun, F. Schatz, N. Mackman, S. Guller, and C. J. Lockwood Transcriptional Regulation of the Tissue Factor Gene by Progestins in Human Endometrial Stromal Cells J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 926 - 930. [Abstract] [Full Text]
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R. Runic, F. Schatz, L. Krey, R. Demopoulos, S. Thung, L. Wan, and C. J. Lockwood Alterations in Endometrial Stromal Cell Tissue Factor Protein and Messenger Ribonucleic Acid Expression in Patients Experiencing Abnormal Uterine Bleeding While Using Norplant-2 Contraception J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1983 - 1988. [Abstract] [Full Text] [PDF]
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