Disease relevance of Medroxyprogesterone acetate

• Similarly, human breast cancer cell lines are arrested in G1 but not G0 phase by medroxyprogesterone acetate (MPA) or tamoxifen exposure [1].
• In an attempt to understand the antiproliferative effects of progestins in endometrial cancer, we have examined the effects of the potent progestin, medroxyprogesterone acetate (MPA), on the cell proliferation and the expression of transforming growth factor (TGF) alpha and beta genes in human endometrial adenocarcinoma cell lines [2].
• Primary cultures of the MPA-induced carcinomas C4-HD and C7-HI were set up, and after 3-4 months, several different cell lines were obtained [3].
• Northern blot hybridization using 32P-labeled human prepro-EGF complementary DNA was carried out for nonpregnant human endometria from hysterectomized uteri of leiomyoma, decidua from early pregnancy, and in vitro decidualized endometrial cells by medroxyprogesterone acetate (MPA) [4].
• Reports indicate that medroxyprogesterone acetate (MPA) is clinically effective in alleviating pelvic pain in the majority of endometriosis patients, which leads us to hypothesize that MPA may be antiinflammatory [5].

Psychiatry related information on Medroxyprogesterone acetate

• Medroxyprogesterone acetate (MPA) treatment of sexual acting out in men suffering from dementia [6].
• All these groups also received 2.5 mg of medroxyprogesterone acetate (MPA) sequentially for the last 12 days of HRT, while the fourth therapy group received 0.625 mg/d of CEE and 2.5 mg/d of MPA continuously (n = 19) [7].
• A case history was presented of a young man with mild mental retardation who was successfully treated with MPA [8].

High impact information on Medroxyprogesterone acetate

• Treatment of C4HD cells with MPA induced Stat3 binding to DNA [9].
• While expression of Stat3Y705-F mutant had an inhibitory effect on MPA-induced growth of C4HD cells, transfection with the constitutively activated Stat3-C vector resulted in MPA-independent proliferation [9].
• In vitro, MC4-L2 and MC7-L1 were stimulated by MPA (nM to microM) and 17beta-estradiol (nM and 10 nM); no significant stimulation was observed in MC4-L1, MC4-L3, and MC4-L5 under the same experimental conditions [3].
• When the cells were removed from MPA, TGF-alpha expression declined gradually, but EGF-receptor mRNA levels increased, as did EGF-binding activity [10].
• MPA had no effect on TGF-alpha expression by HEC-50 cells [2].

Chemical compound and disease context of Medroxyprogesterone acetate

• In the present study, we explored the capacity of progestins to modulate Stat3 transcriptional activation in an experimental model of hormonal carcinogenesis in which the synthetic progestin medroxyprogesterone acetate (MPA) induced mammary adenocarcinomas in BALB/c mice and in the human breast cancer cell line T47D [9].
• A randomized comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer [11].
• RESULTS: Among users of estrogen with medroxyprogesterone acetate (MPA) 10 to 24 days/month, women who took >100 mg/month had an endometrial cancer risk that was equal to that of hormone nonusers (95% CI 0.6-1.7) [12].
• Experiences with doxo/epirubicin and medroxyprogesterone acetate (MPA) in prostatic cancer [13].
• Oral treatment with 0.1mg medroxyprogesterone acetate (MPA) per kg body weight, once daily, was started and continued until Day 58 in order to prevent abortion due to progesterone deficiency [14].

Biological context of Medroxyprogesterone acetate

• To investigate the correlation between MPA-induced Stat3 activation and cell growth, C4HD cells were transiently transfected with a DN Stat3 expression vector, Stat3Y705-F, or with a constitutively activated Stat3 mutant, Stat3-C [9].
• In addition, MPA induced rapid, nongenomic Stat3, Jak1, and Jak2 tyrosine phosphorylation in C4HD and T47D cells [9].
• Incubation of both cell lines with MPA resulted in a time- and dose-dependent inhibition of cell proliferation [2].
• Conversely, silencing of FOXO1 expression completely abolishes cell death induced by MPA withdrawal [15].
• However, MPA treatment of T-47D cells resulted in a 55% decrease in overall AP-1 activity, as measured by transient transfection of an AP-1-regulated chloramphenicol acetyltransferase reporter gene [16].

Anatomical context of Medroxyprogesterone acetate

• We found that C4HD epithelial cells, from the MPA-induced mammary tumor model, expressed Stat3 and that MPA treatment of C4HD cells up-regulated Stat3 protein expression [9].
• Treatment with conjugated equine estrogens, but not MPA, augmented endothelium-mediated dilation of atherosclerotic coronary arteries [17].
• Although no hybridized band was found in the proliferative and secretory phase endometria, a specific band of 5 kilobases, in agreement with the size of human prepro-EGF messenger ribonucleic acid, was detected in decidua of early pregnancy as well as in in vitro MPA-induced decidual cells [4].
• In the cultured stromal cells, Northern analysis revealed a 4-fold increase in steady state levels of PAI-1 mRNA in response to 10(-6)-10(-8) mol/L MPA [18].
• Medroxyprogesterone acetate (MPA) in advanced granulosa cell tumours of the ovary--a new therapeutic approach [19]?

Associations of Medroxyprogesterone acetate with other chemical compounds

• A significant decrease in TGF-alpha mRNA was apparent 6 h after exposure to MPA and a further decrease was seen 12-24 h after addition of the progestin [2].
• Our results also demonstrated that induction of steady state TF mRNA by MPA was abolished by treating cells with E2 plus MPA in conjunction with the protein synthesis inhibitor cycloheximide [20].
• Polyacrylamide gel electrophoretic separation after immunoprecipitation of biosynthetically labeled PAs revealed that medroxyprogesterone acetate (MPA) lowered levels of secreted tissue type PA (tPA) at 67 kilodaltons and urokinase type PA (uPA) at 55 kilodaltons [21].
• LDL was isolated from monkeys fed an atherogenic diet for 12 weeks or the same diet with CEE, MPA, CEE + MPA, or tamoxifen added at levels equivalent (on a caloric basis) to those given to women [22].
• In these last lines the synthetic glucocorticoid, dexamethasone, was a more potent inducer of EGF binding than MPA, a known glucocorticoid agonist, while the high-affinity PR ligand, ORG 2058, was without effect [23].

Gene context of Medroxyprogesterone acetate

• Recent data suggest that the presence of structurally altered AR in breast cancers may account for unresponsiveness to MPA in some of these cases [24].
• VEGF production was also significantly greater in cells treated with db-cAMP (0.5 mmol/L) and MPA (1 nmol/L or 100 nmol/L) than in control cells [25].
• HRG induced a potent proliferative effect on these cells and potentiated MPA mitogenic effects [26].
• The level of TGF beta 3 mRNA in endometrial stromal cells, however, was decreased by MPA treatment [27].
• Treatment of stromal cells with medroxyprogesterone acetate (MPA, a synthetic progestin) also effected a small increase in the level of TGF beta 1 mRNA [27].

Analytical, diagnostic and therapeutic context of Medroxyprogesterone acetate

• MPA decreased jun-B mRNA levels 50% 1 h after treatment in T-47D cells.(ABSTRACT TRUNCATED AT 250 WORDS)[16]
• Furthermore, confocal laser microscopy experiments demonstrated that MPA was able to induce co-localization of ErbB-2 and IGF-IR [28].
• Use of RT-PCR to augment the sensitivity of mRNA detection revealed the presence of type I mRNA as a faint band in the MPA-treated cultures and as an intense band in the E2- plus MPA-treated cultures [29].
• Fifty women received oral administration of 0.625 mg of conjugated equine estrogen (CEE) and 2.5 mg of medroxyprogesterone acetate (MPA) every other day, and 49 women received oral administration of 0.625 mg of CEE and 2.5 mg of MPA every day [30].
• Fifty-seven patients were randomised to receive second-line treatment with either medroxyprogesterone acetate (MPA), oral chlorambucil or combination chemotherapy (adriamycin + cyclophosphamide + 5-fluoro-uracil) [31].

References