FSH receptor binding inhibitor restrains follicular development and possibly attenuates carcinogenesis of ovarian cancer through down-regulating expression levels of FSHR and ERβ in normal ovarian tissues

Objectives: The current study aimed to investigate FSH receptor binding inhibitor (FRBI) effects in the expressions of FSH receptor (FSHR) and estrogen receptor-beta (ER beta) in the mice ovaries at the gene and protein levels, also to find the potential efficacy of FRBI on suppressing ovarian cancer through down-regulating over-expression of FSHR and ER beta in the normal ovarian tissues. Methods: 180 female mice were randomized into six groups (n = 30). Mice of FRBI-1, FRBI-2 and FRBI-3, FRBI-4 were intramuscularly injected with FRBI of 10, 20, 30 and 40 mg/kg, respectively, for five consecutive days. The qPCR and Western blotting were used to determine expression levels of FSHR and ER beta mRNAs and proteins in mouse ovaries. Results: The ovarian cortex thickness (OCT) of the FRBI-4 group were less than that FSH group on day 30 (P < 0.05). The numbers of secondary follicles (SF) and the maximum transverse diameters (MTD) of secondary follicles of FRBI-3 and FRBI-4 groups were decreased as compared to FSH group (P < 0.05 or P < 0.01) by 24.11% and 27.47% on day 20 based on the control group (CG) levels. On day 15, the reductions of FSHR mRNA levels in FRBI-2, FRBI-3 and FRBI-4 were 27.78%, 29.37% and 43.65% (P < 0.05 or P < 0.01), respectively in comparison with CG. ER beta and FSHR protein levels of FRBI-treated mice were gradually decreased as compared to and CG and FSH group. ER beta protein level of FRBI-4 was less than that of CG on day 20 (P < 0.05). On days 15 and 20, estradiol (E-2) concentrations of FRBI-2, FRBI-3 and FRBI-4 groups were lower than those of the CG and FSH group (P < 0.05 or P < 0.01). Conclusions: FRBI could reduce OCT and follicle numbers. A high dose of FRBI (30 mg/kg to 40 mg/kg) could suppress ovarian and follicular development, and attenuate expression levels of ER beta and FSHR mRNAs and proteins in the ovaries, additionally inhibit E-2 production. Therefore, FRBI will possibly be utilized to restrain the carcinogenesis of ovarian cancer by down-regulating overexpression of FSHR and ER beta in the ovaries.