Mechanisms of Bushen Zhuyun Decoction Regulating Pituitary Cell GnRH Receptor and Downstream cAMP-PKA Signaling Pathway in Treating Infertility Due to Luteal Phase Defect
Mechanisms of Bushen Zhuyun Decoction Regulating Pituitary Cell GnRH Receptor and Downstream cAMP-PKA Signaling Pathway in Treating Infertility Due to Luteal Phase Defect
Bei Liu1, Yanli Hong1, Huifang Zhou1,*, Zhenzhen Cao1, Shuang Zhang1, Jing Jin1, Miao Jiang1, Cunsi Shen2 and Jianjian Ji2
ABSTRACT
To observe the effect of Bushen Zhuyun Decoction (BSZYD) on rat pituitary cells (RFC), and to investigate the mechanism of BSZYD in treating infertility due to luteal phase defect (LPD), a GnRH-receptor (GnRHR) antagonized model of pituitary cells was established by using the blocking agent of Cetrorelix. The cells were treated with BSZYD-containing cerebrospinal fluid (CSF). Thus, a total of five groups of cells, including blank (+) group, Cetrorelix (+) group, CSF with BSZY (+) group, model-treated (+) group and corresponding blocker-treated group were established. Secretion levels of related hormone and their mRNAs were detected in the supernatant of each group. The mRNA and protein levels of GnRHR, the hub genes and key transcription factors in the downstream cAMP-PKA signaling pathways in RPC cells were also detected. The secretion and transcription levels of FSH and LH in Cetrorelix group were significantly decreased, while the expression of GnRHR was significantly increased compared to the blank group (p<0.05). Use of CSF with BSZYD alone showed no significant effect on the secretion of RPC, and the expressions of GnRHR and related hub genes in cAMP-PKA pathway. However, it exerted an effect on the model-treated group. Further, no significant difference was found in the content of cAMP and the levels of mRNA and protein of PKA in the supernatant between model-treated group and Cetrorelix group, while there was significant difference in the expression of CREB and Egr-1 between the two groups (p<0.05). Pituitary is one of the effective targets of BSZYD. BSZYD, by interacting with the GnRHR of pituitary gland, can activate cAMP-PKA signal transduction pathway, and in turn affect the downstream factors CREB and Egr-1 to regulate the secretion and transcription of FSH and LH. This pharmacological mechanism can redress luteal function and improve endometrial receptivity, and thus increase the clinical pregnancy rate.
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April 2019
Vol. 51, Iss. 2, Pages 399-799
