Effect of a Traditional Chinese Medicine Formula (Bu Shen Zhu Yun) on Mifepristone-Induced Abnormal Pituitary Gonadotropin Secretion in Rats

Mifepristone is effective in contraception and does not affect the menstrual cycle. However, the side effects of mifepristone on sex hormones persist after drug discontinuation, possibly leading to luteal phase defect (LPD) and infertility. Recent studies revealed that mifepristone not only affects the ovary and uterus, but also the pituitary, resulting in LPD. Bu Shen Zhu Yun formula (BSZYF) was developed by Professor Guicheng Xia, a "great master in TCM." It effectively cures LPD, while its effect on the pituitary is unclear. In this study, we aimed to explore the effect of BSZYF on gonadotropins and gonadotropin-releasing hormone receptor (GnRHR) signaling transduction in mifepristone-induced LPD rats. To explore the effect of BSZYF on the pituitary in mifepristone-induced LPD rats, SD female rats were administered mifepristone suspension via oral gavage, followed by pharmaceutical intervention. Then, the serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were detected by ELISA, FSH beta and LH beta expression levels in the pituitary were determined by qPCR, and GnRHR expression levels were assessed by qPCR and western blot analysis. Simultaneously, transcription factors, such as c-Jun, Elk-1, Egr-1, Nur77, CREB, and transduction molecules in PKC-MAPK, Ca2+-CAM, and cAMP-PKA signaling pathways, such as PKC, p38mapk, ERK, CAM, and PKA were assessed by realtime PCR and western blot analysis. BSZYF increased the serum FSH levels suppressed by mifepristone (P<0.05). Moreover, the expression of c-Jun, Elk-1, Egr-1, CREB, PKA, p38mapk, JNK, ERK, and PKA was significantly up-regulated in the BSZYF group compared with that in the mifepristone group (P<0.05). However, there was no statistical difference in Nur77 and CAM expression between the blank, mifepristone, and BSZYF groups. BSZYF could regulate abnormal pituitary gonadotropin secretion and GnRHR signaling transduction systems induced by mifepristone.