Abstract
Purpose: To determine the effect of Bu-Shen-Zhu-Yun Decoction (BSZY-D) on the kisspeptin through JAK2/STAT5 signaling pathway in hyperprolactinemia (HPRL) infertility.Method: SD rats were treated with BSZY-D for cerebrospinal fluid (CSF) extraction. GT1-7 cells were subjected to different treatments. The phosphorylation levels of JAK2 and STAT5, and the expressions of PRLR and kisspeptin of GT1-7 cells in different groups were detected by western blot, RT-qPCR and immunofluorescence. The expressions of CSN5 and GATA1 and other molecular features were checked by western blot, RT-PCR, co-immunoprecipitation and renilla luciferase activity.Results: The phosphorylation levels of JAK2 and STAT5, and the expressions of PRLR and kisspeptin in the HPRL group were significantly decreased, and these changes could be reversed after BSZY-D treatment. In addition, the presence of PRLR deubiquitination was detected in the HPRL group, which could be reversed by shRNA-CSN5, suggesting that BSZY-D played a role through targeting CSN5. The binding level of GATA1 and CSN5 promoter in the HPRL group was significantly decreased, but elevated in the HPRL (BSZY-D/CSF) group (P < 0.05).Conclusion: BSZY-D improved the transcription activity of GATA1 and increased the binding of GATA1 and CSN5. BSZY-D was involved in the deubiquitination of PRLR, which contributes to alleviating the symptoms of HPRL infertility.
Highlights
Hyperprolactinemia (HPRL) is caused by a variety of factors and characterized by the significant elevation of serum prolactin (PRL)
The phosphorylation levels of JAK, signal transducer and activator of transcription 5 (STAT5), and the levels of PRLR and kisspeptin of GT1-7 cells in different groups were detected by western blot (Figure 1)
Our data represented that compared with the Control group, the phosphorylation levels of Janus kinase 2 (JAK2) and STAT5, and the levels of PRLR and kisspeptin in the PRL (100 ng/ml and 200 ng/ml) group were significantly decreased (P < 0.05)
Summary
Hyperprolactinemia (HPRL) is caused by a variety of factors and characterized by the significant elevation of serum prolactin (PRL). It is a syndrome of reproductive-endocrine disorder in the hypothalamicpituitary axis, with relatively high morbidity [1]. There is no consistent detection method or reference range among different hospitals, it is widely accepted that the subject with serum PRL value more than 1.4 nmol/L should be diagnosed as HPRL [2]. The main clinical symptoms include galactorrhea, menstrual disorders, hirsutism, and even infertility [4]. Nowadays, the medication such as bromocriptine is mostly applied in clinical practice. It is necessary to explore more safe and effective therapeutic strategies for patients with HPRL infertility
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