FF-MAS Oksisterolünün Folikülogenezdeki Rolünün ve Hedgehog Sinyal Yolağıyla İlişkisinin İncelenmesi

Abstract

FF-MAS oxysterol is a derivative of steroid, found in follicular fluid and involved in oocyte maturation. Hedgehog pathway is one of the many cell signaling mechanisms effective in cell proliferation and its effect on the maturation of oocytes has been demonstrated. The effect of Hedgehog ligands in the cell, begins with binding and inhibiting the negative regulatory protein Ptch. Ptch inhibition performs the activation of positive regulatory receptor SMO then activation of the transcription factor Gli1, thus it initiate transcription of the target genes. Granulosa cells are critical cells in follicular development. Cumulus-oocyte complex displaced from Graaf follicle in ovulation; it includes oocyte and granulosa cells. Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders today, in which follicular development cannot progress, and resultant cystic follicles are observed. The aim of this research is to investigate the effect of FF-MAS, which plays a role in folliculogenesis, on granulose cell proliferation through Hedgehog pathway molecules SMO and Gli1. For this purpose; the effect of FF-MAS and pathway inhibitor cyclopamine on SMO and Gli1 expressions was evaluated in cell cultures of granulosa cells from healthy and PCOS patient women. SMO and Gli1 immunohistochemistry expressions and quantitative cytoELISA evaluations showed that FF-MAS increased these expressions, while cyclopamine decreased the expressions statistically. These results show that in the presence of FF-MAS oxysterol the Hedgehog pathway is more activated than the control. In addition, cells of PCOS patients respond at a higher rate to FF-MAS. These data suggest that the FF-MAS - Hedgehog and other cell signaling pathway relationships should be evaluated in vivo in other studies.