ABSTRACT
Experiments were conducted to determine if the follicle-stimulating hormone (FSH) receptor binding inhibitor (FRBI) impacts the expression levels of AT-rich interactive domain-containing protein 1A (ARID1A) and phosphatase and tensin homolog (PTEN) in ovaries and blood, as well as expressions of follicle-stimulating hormone cognate receptor (FSHR) gene and proteins. Mice in FRBI-10, FRBI-20, FRBI-30, and FRBI-40 groups were intramuscularly injected with 10, 20, 30, and 40 mg FRBI/kg, respectively, for five consecutive days. Western blotting and qRT-PCR were utilized to determine expression levels of ARID1A and PTEN proteins and mRNAs. Serum ARID1A and PTEN concentrations of the FRBI-40 group were higher than the control group (CG) and FSH group (P<0.05). FSHR mRNA levels of FRBI-20, FRBI-30, and FRBI-40 groups were lower than that of CG and FSH groups on day 15 (P<0.05 or P<0.01). Expression levels of FSHR proteins of FRBI-30 and FRBI-40 groups were lower than those of CG and FSH groups (P<0.05). Levels of ARID1A and PTEN proteins of the FRBI-30 group were greater than CG on days 20 and 30 (P<0.05). FRBI doses had significant positive correlations to levels of ARID1A and PTEN proteins. Additionally, ARID1A and PTEN had negative correlations to FSHR mRNAs and proteins. A high dose of FRBI could promote the expression levels of ARID1A and PTEN proteins in ovarian tissues. FRBI increased serum concentrations of ARID1A and PTEN. However, FRBI depressed expression levels of FSHR mRNAs and proteins in mouse ovaries.
Subject(s)
Animals , Female , Rabbits , Ovarian Neoplasms/metabolism , Receptors, FSH/antagonists & inhibitors , Nuclear Proteins/blood , DNA-Binding Proteins/metabolism , PTEN Phosphohydrolase/blood , Follicle Stimulating Hormone/metabolism , Phosphorylation , Transcription Factors , Nuclear Proteins/metabolism , Transcriptional Activation/genetics , Up-Regulation , Blotting, Western , DNA-Binding Proteins/blood , PTEN Phosphohydrolase/metabolism , Real-Time Polymerase Chain ReactionABSTRACT
Follicle stimulating hormone receptor is used as an imaging biomarker for the detection of ovarian cancer (OC). Inhibiton of FSHR may attenuate the carcinogenesis particularly epithelial ovarian cancer. Here we investigated FSH receptor binding inhibitor (FRBI) effects on the follicular development, to explore their impact on expressions of FSH receptor (FSHR) and estrogen receptor b (ERβ) proteins in the ovaries. 150 female mice were assigned to FRBI+FSH (COM) group, FSH group, and control group (CG). Mice in COM-1, COM-2, and COM-3 groups were intramuscularly injected with 500, 750 and 1000 μg FRBI combined with 10 IU FSH for five consecutive days. The results showed that the numbers of secondary follicles (SF) in FSH group were increased. SF numbers of three COM groups were gradually declined as the FRBI doses rose. SF numbers of COM-2 and COM-3 groups were less than the FSH group on day 20 (P <0.05). Ovarian cortex thicknesses (OCT) of COM-3 group was less than that FSH group (P <0.05). Maximum longitudinal diameter (MLD) and transverse diameter (MTD) of SFs in three COM groups were dose-dependently decreased. FSHR protein levels of COM groups were significantly decreased as compared to FSH group (P <0.05). ERβ protein levels of COM-1 and COM-2 were less than the FSH group (P <0.05). Summarily, FRBI could reduce OCT and follicle numbers, suppress follicular development, decrease expression of ovarian ERβ and FSHR protein.