scholarly journals Progesterone receptor antagonist provides palliative effects for uterine leiomyoma through a Bcl-2/Beclin1-dependent mechanism

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Lindong Zhang ◽  
Quanling Feng ◽  
Zhiting Wang ◽  
Pingping Liu ◽  
Shihong Cui
Keyword(s):  
Progesterone Receptor ◽  
Receptor Antagonist ◽  
Uterine Leiomyoma ◽  
Lentiviral Vector ◽  
Smooth Muscle Tumor ◽  
Reproductive Age ◽  
M Cells ◽  
Promising Therapeutic Target ◽  
Dependent Mechanism

Abstract Uterine leiomyoma is the most common benign smooth muscle tumor of uterus in women of reproductive age, with a high lifetime incidence. Nowadays, the exploration on the pharmacotherapies, such as progesterone receptor antagonist (PRA) requires more attention. Hence, the current study aimed to examine whether mifepristone, a PRA, influences the autophagy and apoptosis of uterine leiomyoma cells. Primary uterine leiomyoma cells were collected from 36 patients diagnosed with uterine leiomyoma to establish PR-M-positive (PR-M[+]) cells. The lentiviral vector overexpressing or silencing PR-M was subsequently delivered into one part of PR-M(+) cells in order to evaluate the role of PR-M in PR-M(+) cells. The results obtained revealed that cell viability was increased, while cell autophagy and apoptosis were diminished in the PR-M(+) cells treated with overexpressed PR-M, whereby the Bcl-2 level was elevated and the level of Beclin1 was reduced. An opposite trends were identified following treatment with knockdown of PR-M. Mifepristone at different concentrations (low, moderate, or high) was then applied to treat another part of the PR-M(+) cells. Mifepristone was identified to promote cell autophagy and apoptosis, decrease Bcl-2 level and increase Beclin1 level, accompanied by weakened interaction between Bcl-2 and Beclin1. Moreover, these effects of mifepristone on PR-M(+) cells were enhanced with increasing of the concentration. Taken together, the present study present evidence indicates the ability of PRA to regulate the Bcl-2/Beclin1 axis, ultimately promoting the autophagy and apoptosis of uterine leiomyoma cells, highlighting that PRA serves as a promising therapeutic target for the treatment of uterine leiomyoma.

Role of WNT4, HOXA10 and TWIST1 genes in the pathogenesis of external genital endometriosis and uterine leiomyoma

2021 ◽  
Vol 70 (3) ◽  
pp. 31-40
Author(s):  
Olga V. Malysheva ◽  
Arseny S. Molotkov ◽  
Natalya S. Osinovskaya ◽  
Natalya Yu. Shved ◽  
Maria I. Yarmolinskaya ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Real Time ◽  
Real Time Pcr ◽  
Uterine Leiomyoma ◽  
Comparison Group ◽  
Reproductive Age ◽  
Cycle Phase ◽  
Transcription Analysis ◽  
Polymorphic Variants

BACKGROUND: Uterine leiomyoma and endometriosis are the most common gynecological diseases in women of reproductive age. A number of data indicate that there are common elements in the pathogenesis of these hyperproliferative conditions. This article is devoted to comparative analysis of the role of the WNT4, HOXA10 and TWIST1 genes in the development of uterine leiomyoma and external genital endometriosis. AIM: The aim of this study was to evaluate the frequency of polymorphic variants rs7521902 (WNT4) and rs4721745 (TWIST1) in patients with uterine leiomyoma, external genital endometriosis and in the comparison group; to determine the frequency of rare allelic variants of the HOXA10 gene in patients with external genital endometriosis; and to study the expression of these genes in the endometrium in patients with uterine leiomyoma, EGE and in the comparison group. MATERIALS AND METHODS: The polymorphic variants of the WNT4 and TWIST1 genes were studied by real-time PCR in patients with external genital endometriosis, uterine leiomyoma and in the comparison group. In patients with EGE and women in the comparison group, the second exon of the HOXA10 gene was sequenced. Real-time PCR with reverse transcription analysis of the expression of the WNT4, TWIST1 and HOXA10 genes in endometrial samples from the patients of the study groups was performed. RESULTS: The frequencies of polymorphic variants rs7521902 (WNT4) and rs4721745 (TWIST1) in patients with uterine leiomyoma, external genital endometriosis and in the comparison group did not differ significantly. Minor alleles of the HOXA10 gene were not identified in patients with external genital endometriosis. Expression of the WNT4 gene in the endometrium of patients with external genital endometriosis was independent of menstrual cycle phase and was reduced by 1.9 times compared to the endometrium of women with uterine leiomyoma. Expression of the HOXA10 gene in the endometrium of endometriosis patients on days 20-23 of the menstrual cycle was significantly reduced compared to the women in the comparison group. Expression of the TWIST1 gene was not altered in the endometrium of patients with uterine leiomyoma and external genital endometriosis. CONCLUSIONS: We did not identify associations of the studied polymorphic variants of the WNT4 and TWIST genes and minor variants of the HOXA10 gene with uterine leiomyoma and external genital endometriosis. The expression of the WNT4 and HOXA10 genes is reduced in the endometrium in patients with external genital endometriosis, but not in women with uterine leiomyoma. Changes in expression patterns of the studied genes in the endometrium differ significantly in these two diseases.

Activin A in Inflammation, Tissue Repair, and Fibrosis: Possible Role as Inflammatory and Fibrotic Mediator of Uterine Fibroid Development and Growth

2017 ◽  
Vol 35 (06) ◽  
pp. 499-509 ◽  
Author(s):  
Olga Protic ◽  
Md Islam ◽  
Stefania Greco ◽  
Stefano Giannubilo ◽  
Pasquale Lamanna ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tissue Repair ◽  
Uterine Leiomyoma ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Tissue Injury ◽  
Hormone Secretion ◽  
Activin A ◽  
Reproductive Age

AbstractThe growth factor activin A belongs to the transforming growth factor-β superfamily and was initially isolated as an inducer of follicle-stimulating hormone secretion. Activin A was later found to play roles in cell proliferation, differentiation, apoptosis, and metabolism. More recently, activin A has also been recognized as a novel player in mediating inflammation, immunity, wound repair, and fibrosis. Elevated levels of activin A during inflammation are responsible for the increased production of extracellular matrix in different pathological conditions, including fibroids. Our group has demonstrated a profibrotic role of activin A in leiomyoma growth. Uterine leiomyoma can be considered as a fibrotic disorder that initiates from myometrial smooth muscle layer of uterus in reproductive-age women and that is driven by a strong inflammatory component. In fertile women, transient inflammation is a physiological and essential process during menstruation, ovulation, and parturition. However, tissue injury from extravasated menstrual blood and/or an altered response to harmful stimuli, such as pathogens, damaged cells, or irritants, can establish chronic inflammation in the uterus, ultimately leading to dysregulated tissue repair. Myofibroblasts are key cells in normal repair and the chronic tissue remodeling characteristic for fibrosis and uterine leiomyoma. In this review, we discuss the role of activin A in inflammation, tissue repair, and fibrosis and we elaborate the hypothesis that it plays a central role in myofibroblast activation and leiomyoma development and growth.

scholarly journals Effect of transforming growth factor-β2 on uterine leiomyoma cells proliferation

2015 ◽  
Vol 96 (6) ◽  
pp. 968-970
Author(s):  
N D Muratova ◽  
A A Abduvaliev
Keyword(s):  
Growth Factor ◽  
Cytotoxic Activity ◽  
Uterine Leiomyoma ◽  
Transforming Growth Factor ◽  
Uterine Fibroids ◽  
Uterine Myoma ◽  
Reproductive Age ◽  
Culture Cells ◽  
Transforming Growth Factor Β2

Aim. To study the role of transforming growth factor-β2 in the uterine leiomyoma pathogenesis. Methods. Studies to determine the cytotoxic activity of the transforming growth factor-β2 regarding the temporary cell culture were conducted. The operational material was used from two women of reproductive age with uterine myoma (multiple symptomatic uterine myoma, proliferative type) who underwent hysterectomy. Patients mean age was 43.5±0.57. Obtained temporary culture cells were split into five groups depending on the transforming growth factor-β2 affecting dose (1000, 500, 100, 10 µg/10×106, and culture with no exposure). After incubation living and dead cells were counted at 280 times magnification. The cytotoxic activity was expressed as a percentage of live and dead cells. Results. Total cell death (necrosis) was 23.0% when using factor at the dose 10 µg/10×106 cells, at the dose 100 µg/ 10×106 cells - 34.5%, at the dose 500 µg/10×106 cells - 44%, at the dose 1000 µg/10×106 cells - 59.5%. The most effective vital life suppressing activity of the transformed cells was observed when exposed to transforming growth factor-β2 at the dose 1000 µg/10×106 cells. Conclusion. Transforming growth factor-β2 is capable to suppress the proliferating uterine fibroids growth under certain conditions and the dose, it has a significant dose-dependent cytotoxic effect in respect of the neoplasm.

Oestrogen and Progesterone Receptor Concentrations in Leiomyoma and Normal Myometrium

1987 ◽  
Vol 24 (3) ◽  
pp. 263-267 ◽  
Author(s):  
O Sadan ◽  
B Van Iddekinge ◽  
C J Van Gelderen ◽  
N Savage ◽  
P J Becker ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Progesterone Receptor ◽  
Uterine Leiomyoma ◽  
Progesterone Receptors ◽  
Reproductive Age ◽  
Women Of Reproductive Age ◽  
Receptor Level ◽  
First Report ◽  
Steroid Dependence ◽  
High Concentrations

The content of cytoplasmic 17β oestradiol and progesterone receptors in human uterine leiomyoma and normal myometrium in the Negroid population was determined. Eighteen women of reproductive age, at various stages of the menstrual cycle, were included in the study. The serum oestrogen and progesterone concentrations were also measured. This is the first report in the literature in which oestrogen and progesterone receptors in leiomyoma are significantly higher than in normal myometrium ( P=0·0002). The steroid dependence of the growth of leiomyomas may be related to the steroid receptor level. The presence of persistently high concentrations of oestrogen and progesterone receptors in leiomyoma should be helpful in the treatment of this benign tumour.

The Role of Vitamin B6 in Reducing Serum Prolactin in Comparison to Cabergoline

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Suha J. Witwit
Keyword(s):  
Prolactin Level ◽  
Vitamin B6 ◽  
Reproductive Age ◽  
Serum Prolactin ◽  
Polycystic Ovaries ◽  
Endocrine Disorder ◽  
Hypothalamic Pituitary Axis

Hyperprolactinemia is a common endocrine disorder of hypothalamic-pituitary axis. It affect about 4-17% of women in reproductive age and about 3-10% of patients with polycystic ovaries. Vitamin B6 is an effective prolactin inhibitor that is extremely cheap and safe.it exerts hypothalamic dopaminergic effect which causes a significant reduction in prolactin level. The aim of the study is To evaluate the effectiveness of vitamin B6 in reducing serum prolactin in Hyperprolactinemic patient. Compare this effect to that of cabergoline.

The role of orexin A in pathophysiological mechanisms of sleep disorder in postmenopausal women

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (1) ◽  
pp. 50-54
Author(s):  
Zukhra Kh. Ebzieva ◽  
Svetlana V. Yureneva ◽  
Tatiana Yu. Ivanets
Keyword(s):  
Hormone Therapy ◽  
Sleep Disorder ◽  
Postmenopausal Women ◽  
Menopausal Hormone Therapy ◽  
Reproductive Age ◽  
Vasomotor Symptoms ◽  
Women Of Reproductive Age ◽  
Orexin A ◽  
Group 1

Aim. To conduct a comparative analysis of serum orexin A levels in women of different age periods with and without sleep disorder and vasomotor symptoms. To evaluate the dynamics of orexin A levels under menopausal hormone therapy. Materials and methods. The study included 50 postmenopausal women and 30 women of reproductive age with a regular menstrual cycle. Using block randomization, patients are divided into 3 groups: group 1 (main group), n=25, -STRAW+ 10 (+1b and +1c), patients with sleep disorder and vasomotor symptoms; group 2 (comparison group), n=25, STRAW+ 10 (+1b and +1c), patients with vasomotor symptoms without sleep disorder; group 3 (control group), n=30, STRAW+ 10 (-4), women of reproductive age without sleep disorder. Group 1 patients were given menopausal hormone therapy. A comparative analysis was carried out using the questionnaire for assessing menopausal symptoms severity by the Greene Scale (the Greene Climacteric Scale) and Rating Scale for subjective sleep characteristics. After 12 weeks of treatment, a control examination was performed. Results. In group 1 women, the serum orexin A levels were significantly higher compared to the women without the symptoms. The link between the orexin A levels and menopause syndrome severity was established. A significant decrease in the menopausal symptoms severity after 12 weeks of menopausal hormone therapy was shown. It was accompanied by a 1,3-fold decrease in orexin A levels. Conclusions. The obtained data indicate the possible role of orexin A and the orexin neuropeptide system in the pathogenesis of sleep disorder and vasomotor symptoms in postmenopausal women.

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