The Effect of Progestins on the Mitotic Activity of Uterine Fibromyomas

Tiltman, A. J.

doi:10.1097/00004347-198506000-00001

Cited by 132 publications

(65 citation statements)

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“…On the other hand, it is clear that these tumors are subject to hormonal modulation during the cycle, as mitotic activity is reported to be significantly higher during the secretory phase than during the proliferative phase (Kawaguchi et al 1989;Lamminen et al 1992;Nisolle et al 1999). These latter reports are consistent with a study by Tiltman (Tiltman 1985) that demonstrated a significantly higher mitotic activity in the leiomyomas of patients who received a progestin-only preparation. In lone contrast to these studies is an earlier report that had noted no mitotic activity in the myomas of patients given progestin therapy (Goldzieher et al 1966).…”

Section: Review | Uterine Leiomyomasupporting

confidence: 81%

Etiology and pathogenesis of uterine leiomyomas: a review.

Flake

Andersen

Dixon

2003

Environ Health Perspect

494

392

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Uterine leiomyomas, or fibroids, represent a major public health problem. It is believed that these tumors develop in the majority of American women and become symptomatic in one-third of these women. They are the most frequent indication for hysterectomy in the United States. Although the initiator or initiators of fibroids are unknown, several predisposing factors have been identified, including age (late reproductive years), African-American ethnicity, nulliparity, and obesity. Nonrandom cytogenetic abnormalities have been found in about 40% of tumors examined. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has only recently been explored. Growth factors with mitogenic activity, such as transforming growth factor-β 3, basic fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I, are elevated in fibroids and may be the effectors of estrogen and progesterone promotion. These data offer clues to the etiology and pathogenesis of this common condition, which we have analyzed and summarized in this review.

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Section: Review | Uterine Leiomyomasupporting

confidence: 81%

Etiology and pathogenesis of uterine leiomyomas: a review.

Flake

Andersen

Dixon

2003

Environ Health Perspect

494

392

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“…Here we demonstrated that R5020 increased total viable primary LSM cells. Others have also reported that progestins stimulate proliferation and inhibit apoptosis of primary LSM cells, whereas the selective PR modulator asoprisnil inhibits proliferation and induces apoptosis in the same cells (5)(6)(7)(8)(9)(10)(11). Our report further explored the molecular mechanisms by which progestin stimulation of leiomyoma growth occurs.…”

Section: Discussionsupporting

confidence: 51%

“…Several investigators have shown an increased concentration of both PR isoforms (PR-A and PR-B) in leiomyoma tissue, compared with adjacent myometrium (2,3). Furthermore, increases in mitotic activity occur in leiomyoma tissue relative to the adjacent myometrial tissue during the luteal phase and after treatment with medroxyprogesterone acetate (4,5). Additionally, in vitro studies showed that progesterone suppresses apoptosis and stimulates proliferation of leiomyoma smooth muscle (LSM) cells in culture, whereas PR modulators inhibit proliferation and induce apoptosis in these cells (6 -11).…”

Section: Discussionmentioning

confidence: 99%

Progesterone Receptor Regulates Bcl-2 Gene Expression through Direct Binding to Its Promoter Region in Uterine Leiomyoma Cells

Yin

Lin

Cheng

et al. 2007

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context: Uterine leiomyomas are smooth muscle cell tumors that cause irregular uterine bleeding and pregnancy loss in many reproductive-age women. Progesterone stimulates their growth, whereas treatment with progesterone receptor (PR) antagonists or selective progesterone receptor modulators shrinks these tumors. Molecular mechanisms underlying these observations are unknown.Objective: Bcl-2 is a key protein that inhibits apoptosis. It was proposed that growth enhancement of leiomyoma cells by progesterone was mediated via bcl-2 induction. Here we test the hypothesis that PR regulates the bcl-2 gene by directly binding to its promoter. Results:The pure progesterone agonist R5020 increased the total number of viable primary human leiomyoma smooth muscle (LSM) cells in culture. Progesterone or R5020 (10 Ϫ6 M) significantly increased bcl-2 mRNA levels after 2 and 4 h by 9.2-and 3.4-fold, respectively, in LSM cells. Transient transfection with deletion mutants of bcl-2 promoter showed that the Ϫ1281/Ϫ258-bp region conferred responsiveness to progesterone induction in the presence of PR-A. We identified a palindromic progesterone response element (PRE) at Ϫ553/Ϫ539 bp. EMSA showed that PR in nuclear extracts from LSM cells bound specifically to this PRE. Chromatin immunoprecipitation-PCR confirmed in situ recruitment of PR to the Ϫ629/Ϫ388-bp region bearing the PRE. In vivo, bcl-2 mRNA levels correlated significantly with total PR mRNA levels in leiomyoma tissues. Conclusion

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“…Recent data suggest that progestogens, like estrogens, stimulate fibromyoma growth [21]. Estrogen and P receptors have been found in the myometrium and in myomas [22,23]. Myometrial and myoma tissue cultures incubated with P grow significantly [24].…”

Section: Discussionmentioning

confidence: 99%

Short-Term Treatment of Uterine Fibromyomas with Danazol

Leo

Marca²,

Morgante³

1999

Gynecol Obstet Invest

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The aim of this study was to evaluate the effects of danazol in reducing the volume of fibromyomas and in the treatment of associated symptoms. Twenty women (34–42 years) with uterine fibromyomas were treated with 400 mg/day of danazol for 4-month periods. The women underwent ultrasound examination to determine their uterine volume at enrollment in the follicular phase and after 2 and 4 months. The examination was repeated by the same sonographer 3 and 6 months after the end of therapy. Blood samples were taken on the same days for LH, FSH, estradiol and progesterone assays. After therapy, fibromyoma volume decreased significantly (p < 0.01) by an average of 23.6 ± 5%. All patients experienced partial or complete relief of symptoms while using danazol. Three and six months after the end of treatment the fibromyoma volume had only increased slightly with respect to the volume at the end of therapy, but was still lower than the starting volume. The present study shows the efficacy of danazol at a dose of 400 mg/day for 4 months in reducing the volume of fibromyomas and associated symptoms. The mechanism by which danazol reduces the volume of fibromyomas may be due to reduced estrogen concentrations and to its antiprogesterone effects on uterine myomas.

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The Effect of Progestins on the Mitotic Activity of Uterine Fibromyomas

Cited by 132 publications

References 0 publications

Etiology and pathogenesis of uterine leiomyomas: a review.

Etiology and pathogenesis of uterine leiomyomas: a review.

Progesterone Receptor Regulates Bcl-2 Gene Expression through Direct Binding to Its Promoter Region in Uterine Leiomyoma Cells

Short-Term Treatment of Uterine Fibromyomas with Danazol

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