Expression of progesterone receptors A and B and insulin-like growth factor-I in human myometrium and fibroids after treatment with a gonadotropin-releasing hormone analogue

Wu, Xinhui; Wang, Hong; Englund, Katarina; Blanck, Agneta; Lindblom, Bo; Sahlin, Lena

doi:10.1016/s0015-0282(02)03378-2

Cited by 12 publications

(7 citation statements)

References 40 publications

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“…However, Viville et al (1997) failed to ®nd the difference between the concentrations of mRNA encoding PR-A and PR-B in leiomyoma and myometrium, suggesting the post-translational control. In addition, GnRH agonist down-regulates immunoreactive PR, PR-A and PR-B expression, and PR mRNA levels in leiomyoma (Vu et al, 1998;Nisolle et al, 1999;Wu et al, 2002a). Interestingly, Fujimoto et al (1998) have found the relative over-expression of PR-B mRNA in the surface of leiomyoma, suggesting that the predominant expression of PR-B in this part reveals an activated phenotype for progestational proliferation related to the growth of leiomyoma.…”

Section: Progesteronementioning

confidence: 99%

“…Reproduced by permission of The Endocrine Society. ã Copyright 1997 decrease in the binding of EGF to leiomyoma (Lumsden et al, 1988) and immunostaining for EGF-R in leiomyoma (Leone et al, 1991), the decrease in the secretion of IGF-I and IGF-II by explant cultures of leiomyoma (Rein et al, 1990) and IGF-I mRNA levels in leiomyoma (Wu et al, 2002a), and the decrease in the levels of TGFb and its receptors (Dou et al, 1996;Di Lietro et al, 2003). However, con¯icting results exist as to whether GnRH agonist induces apoptosis of leiomyoma cells (Higashijima et al, 1996;Burroughs et al, 1997;Mizutani et al, 1998;Huang et al, 2002).…”

Section: Gnrh Agonist Therapymentioning

confidence: 99%

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Sex steroidal regulation of uterine leiomyoma growth and apoptosis

Maruo¹

2004

Human Reproduction Update

256

196

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Uterine leiomyomas develop during the reproductive years and regress after menopause, indicating ovarian steroid-dependent growth potential. Although the clinical and biochemical observations have traditionally supported an important role for estrogen in the promotion of leiomyoma growth, there is also increasing evidence to suggest the involvement of progesterone in the pathogenesis of leiomyoma. In this review, much attention has been paid to characterizing the molecular mechanisms of sex steroidal regulation of leiomyoma growth and apoptosis by evaluating the effects of sex steroids on the expression of growth factors and apoptosis-related factors. The effects of GnRH agonist on the expression of these factors in leiomyoma are also described. 17beta-Estradiol up-regulates epidermal growth factor (EGF) receptor, but down-regulates p53 protein in leiomyoma cells, whereas progesterone augments EGF and Bcl-2 protein, but inhibits insulin-like growth factor (IGF-I) and tumour necrosis factor (TNFalpha). Since it is now evident that EGF and IGF-I act as local factors which stimulate leiomyoma growth, these findings suggest that progesterone may have dual actions, stimulatory and inhibitory, on leiomyoma cell growth and survival, depending on the local growth factor conditions around each leiomyoma. This may explain why the size of uterine leiomyomas during the use of levonorgestrel-releasing intrauterine system (LNG-IUS) increases in some but decreases in other instances. This may also explain why the size of leiomyomas during pregnancy does not increase despite the overwhelming increase in circulating concentrations of sex steroid hormones. Moreover, there is further evidence to suggest that the interactions between estrogen receptors and progesterone receptors may be involved in the modulation of gene transcription activity in leiomyoma. This review demonstrates that leiomyoma growth is integrally regulated by the complex cross-talk between sex steroid hormones and growth factors.

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Section: Progesteronementioning

confidence: 99%

Section: Gnrh Agonist Therapymentioning

confidence: 99%

Sex steroidal regulation of uterine leiomyoma growth and apoptosis

Maruo¹

2004

Human Reproduction Update

256

196

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“…IGF-I, similarly to progesterone receptor (PR), transcripts in both leiomyoma and myometrium in the proliferative phase were significantly higher than those after GnRH-a treatment, indicating that the leiomyoma fibroid shrinkage after steroid deprivation is associated with alterations in IGF-I and PR expression (Wu et al, 2002). Significantly, decreased IGF-I mRNA and protein expression were observed in cultured leiomyoma cells with the treatment of P 4 either alone or in combination with E 2 , whereas E 2 treatment alone was unable to cause any significant effect, demonstrating a role for P 4 in modulating IGF-I expression in leiomyoma (Yamada et al, 2004).…”

Section: Steroid Regulationmentioning

confidence: 99%

Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications

Ciarmela

Islam

Reis

et al. 2011

Human Reproduction Update

196

175

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“…Leiomyoma pathogenesis is a progestin‐responsive process 8 . Volume decrease of leiomyoma in GnRH agonist‐treated patients is associated with alternation in progesterone receptor (PGR) expression 9 …”

Section: Introductionmentioning

confidence: 99%

“…8 Volume decrease of leiomyoma in GnRH agonist-treated patients is associated with alternation in progesterone receptor (PGR) expression. 9 Numerous hormones could influence the hypophyseal-gonadal axis, including oestrogen, progesterone and thyroid hormones (T3, T4, TSH). 10 Progesterone administration might suppress the hypothalamic-pituitary-ovarian axis, which further influences prolactin (PRL) production.…”

Section: Introductionmentioning

confidence: 99%