Effect of Bushen Zhuyun Formula on Pituitary GnRH Receptor and Signal Transduction System in LPD Rats

OBJECTIVE To explore the effect and mechanism of Bushen Zhuyun formula(BSZYF) on gonadotropins and gonadotropin-releasing hormone receptor(GnRHR) signaling transduction in mifepristone-induced LPD rats， and to find the scientific evidence of "heart， kidney and uterus axis" theory of TCM. METHODS 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 assay， the FSHβ and LHβ expression levels in the pituitary were determined by qPCR， and the GnRHR expression levels were assessed by qPCR and Western blot analysis. Simultaneously， transcription factors， such as c-Jun， Elk-1， Egr-1， Nur77 and CREB， and transduction molecules in PKC-MAPK， Ca 2+ -CAM， and cAMP-PKA signaling pathways， such as PKC， p38MAPK， ERK1/2， CAM， and PKA were assessed by qPCR and Western blot analysis. RESULTS After pharmaceutical intervention， 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 were was significantly upregulated 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 among the blank， mifepristone and BSZYF groups (P>0.05). CONCLUSION BSZYF can regulate abnormal pituitary gonadotropin secretion and GnRHR signaling transduction systems induced by mifepristone， which confirms that the prescription can regulate the whole function of the reproductive axis， and explains the consistency of "Heart， kidney and uterus axis" theory in TCM and the concept of the hypothalamus-pituitary-ovary axis in modern medicine