Differential expression of upstream stimulatory factor (USF) 2 variants in eutopic endometria from women with endometriosis: estradiol regulation

BACKGROUND: Endometriosis, pro-inflammatory and invasive benign disease estrogen dependent, abnormally express in endometria the enzyme P450Arom, positively regulated by steroid factor-1 (SF-1). Our objective was to study the nuclear protein contents of upstream stimulating factor 2 (USF2a and USF2b), a positive regulator of SF-1, throughout the menstrual cycle in eutopic endometria from women with and without (control) endometriosis and the involvement of nuclear estrogen receptors (ER) and G-coupled protein estrogen receptor (GPER)-1. RESULTS: Upstream stimulating factor 2 protein contents were higher in mid (USF2b) and late (USF2a and USF2b) secretory phase in eutopic endometria from endometriosis than control (p < 0.05). In isolated control epithelial cells incubated with E2 and PGE2, to resemble the endometriosis condition, the data showed: (a) significant increase of USF2a and USF2b nuclear protein contents when treated with E2, PPT (specific agonist for ERa) or G1 (specific agonist for GPER1); (b) no increase in USF2 binding to SF-1 E-Box/DNA consensus sequence in E2-treated cells; (c) USF2 variants protein contents were not modified by PGE2; (d) SF-1 nuclear protein content was significantly higher than basal when treated with PGE2, E2 or G1, stimulation unaffected by ICI (nuclear ER antagonist); and (e) increased (p < 0.05) cytosolic protein contents of P450Arom when treated with PGE2, E2, PPT or G1 compared to basal, effect that was additive with E2 + PGE2 together. Nevertheless, in endometriosis cells, the high USF2, SF-1 and P450Arom protein contents in basal condition were unmodified. CONCLUSION: These data strongly suggest that USF2 variants and P450Arom are regulated by E2 through ERa and GPER1, whereas SF-1 through GPER1, visualized by the response of the cells obtained from control endometria, being unaffected the endogenously stimulated cells from endometriosis origin. The lack of E2 stimulation on USF2/SF-1 E-Box/DNA-sequence binding and the absence of PGE2 effect on USF2 variants opposite to the strong induction that they exert on SF1 and P450 proteins suggest different mechanisms and indirect regulations. The sustained USF2 variants protein expression during the secretory phase in eutopic endometria from women with endometriosis may participate in the pathophysiology of this disease strongly associated with infertility and its characteristic endometrial invasion to ectopic sites in the pelvic cavity.

The Expression of P450arom in Human Ovarian Endometriosis and the Relation Ship with its Estrogen Aabnormal Synthesis Locally / 医学研究杂志

Objective To study the expression of P450arom(P450A)protein and mRNA in human ovarian endometriosis and normal endometrium and the relationship with its local estrogen abnormal synthesis.Methods PT-PCR was used to assess P450arom messenger RNA(mRNA)expression of 45 ovarian endometriosis and 35 normal eutopic endometrium;immunohistochemical assay was performed to locate and examin the protein expression of P450arom in the above cases.Results P450A mRNA level was higher in the ectopic endometrium than that in eutopic endometrium(P

Effect of Zhuyunjiaonang on Serum Gonadal Hormone and Expression of P450arom in Polycystic Ovary Syndrome Rats / 中国中医药信息杂志

Objective To observe the effects of Zhuyunjiaonang on morphological change of the ovary, serous hormone and the expression of P450arom in PCO model rats. To explore its target and mechanism in treating PCO model rats. Methods Using INS and HCG to establish PCO model. The PCO rat models were devided into 4 groups randomly, which included control group, model group, Zhuyunjiaonang group and mefformin group. Zhuyunjiaonang group was given 3.0 g/(kg ? d) Zhuyunjiaonang, mefformin group was given 0.75 g/(kg ? d) metformin, control group and model group were given same volume distilled water 1 mL/100 g. The effects of Zhuyunjiaonang on ovaries and ovarial follicular development were observed by light microscope. The levels of serum gonadal hormone were detected by radioimmunoassay. The expression level of P450arom was detected with immtmohistochemical staining technique. Results Zhuyunjiaonang could increase the thickness of granular cell layer and decrease the thickness of theca cell layer, decrease the level of T and LH, and increase the level of FSH and E_2 in serum. Meanwhile the expression of P450arom in ovary were increased. Conclusion Zhuyunjiaonang could indirectly or directly affect the expression of the P450arom in ovary, it could regulate the endocrine function of PCO rat and promote the mature and ovulation of follicular.

Corticotrophin-releasing hormone promotes estrogen synthesis in human placentas / 第二军医大学学报

Objective:To study the effect of corticotrophin-releasing hormone(CRH) on estrogen production in human trophoblasts and its mechanisms. Methods: Cytotrophoblasts were isolated from term human placentas and cultured for 72 h. The cultured cells were then treated with various concentrations of CRH and CRH receptor antagonist,?-Helical CRH9-41 for 24 h; estradiol was measured by radioimmunoassay in the culture media. Expression of aromatase(P450arom),the key enzyme for estrogen synthesis,was analyzed by Northern blot. Results: CRH significantly stimulated estradiol production and the expression of P450arom mRNA in placental cells. It was found that ?-Helical CRH9-41 blocked the effect of CRH and inhibited estradiol production and P450arom mRNA expression(P