Modulation of expression of 17-Hydroxylase/17, 20 lyase (CYP17) and P450 aromatase (CYP19) by inhibition of MEK1 in a human ovarian granulosa-like tumor cell line. (3rd March 2016)

• Record Type: Journal Article
• Authors: Huang, Xiao; Jin, Jiewen; Shen, Shanmei; Xia, Yanjie; Xu, Pei; Zou, Xiang; Wang, Hongwei; Yi, Long; Wang, Yong; Gao, Qian
• Is Part Of: Gynecological endocrinology. Volume 32:Number 3(2016:Mar.)
• Page Start: 201
• Page End: 205
• Publication Date: 2016-03-03
• Subjects: c-fos -- CYP17 -- CYP19 -- KGN -- MEK/ERK; Endocrine gynecology -- Periodicals; Generative organs, Female -- Diseases -- Periodicals; 618.1
• DOI: 10.3109/09513590.2015.1106470
• Languages: English
• ISSNs: 0951-3590

Abstract

Abstract: The differential steroid production in the theca and granulosa cells in ovary are resulted from unique enzyme expression profiles. Among them, c-fos, a downstream target of mitogen and extracellular signal-regulated kinases (MEK/ERK) signaling, takes part in this compartment. In this study, we investigated the effect of c-fos on the steady-state levels of CYP17 and CYP19 in human ovarian granulosa-like tumor cell line (KGN) by inhibiting MEK/ERK pathway with PD98059. As a result, our finding demonstrated the distinct distribution patterns of CYP17 and CYP19 in KGN. Moreover, the MEK/ERK pathway functions to inhibit the production of CYP17, while enhance the production of CYP19 in granulosa cells, probably involving a c-fos-dependent mechanism. In conclusion, factors such as c-fos may play a crucial role in the down-regulation of CYP17 and up-regulation of CYP19 in granulosa cells, thereby suppressing androstenedione synthesis.