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Previous studies have demonstrated that the anti-androgenic effects of cypermethrin (CYP) are associated with testosterone (T) - related signaling pathway. This study was to investigate the effects of CYP on mouse Sertoli cells (TM4) and clarify whether the mechanisms were mediated by non-classical T signaling pathway activating mitogen-activated protein kinase (MAPK) cascade. The Cell Counting Kit 8 (CCK8) and Real-Time Cell Analysis iCELLigence (RTCA-iCELLigence) system were performed to detect the effects of 10 μM, 20 μM, 40 μM and 80 μM CYP on the viability and proliferation of TM4. The mammalian two hybrid assay, quantitative Real-Time PCR (qRT-PCR) and western blot were conducted to analyze the key genes and proteins involved in T-mediated MAPK signaling pathway. CYP was found to inhibit the viability and proliferation of TM4. Additionally, CYP disturbed the functions of Sertoli cells by inhibiting inhibin B (INH B) expression and facilitating androgen binding protein (ABP) and transferrin (TF) expression. Moreover, CYP suppressed the interaction of AR and Src kinase and inhibited androgen-mediated phosphorylation of Src, epidermal growth factor receptor (EGFR), extracellular-regulated kinase1/2 (ERK1/2) and transcription factor cAMP response element binding protein (CREB). Furthermore, the androgen-induced mRNA and protein expression of CREB-regulated gene early growth response factor (Egr1) decreased after treated with CYP. It is indicated that CYP inhibits the viability and proliferation of Sertoli cells and non-classical T signaling pathway activation of MAPK cascade is involved in anti-androgenic effect of CYP. This study provides a novel insight into the CYP-induced reproductive toxicity.
This article was published in the following journal.
Name: Ecotoxicology and environmental safety
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A potent androgenic metabolite of TESTOSTERONE. Dihydrotestosterone (DHT) is generated by a 5-alpha reduction of testosterone. Unlike testosterone, DHT cannot be aromatized to ESTRADIOL therefore DHT is considered a pure androgenic steroid.
Steroidal compounds related to TESTOSTERONE, the major mammalian male sex hormone. Testosterone congeners include important testosterone precursors in the biosynthetic pathways, metabolites, derivatives, and synthetic steroids with androgenic activities.
A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.
A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
A serine protease that cleaves multiple COMPLEMENT 5 into COMPLEMENT 5A (anaphylatoxin) and COMPLEMENT 5B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of CLASSICAL PATHWAY C3 CONVERTASE (C4b2a) with an additional COMPLEMENT C3B, or C4b2a3b.
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