The Localization and Regulation of Proprotein Convertase Subtilisin/Kexin (PCSK) 6 in Human Ovary
Article first published online: 31 AUG 2012
© 2012 John Wiley & Sons A/S
American Journal of Reproductive Immunology
Volume 68, Issue 6, pages 491–498, December 2012
How to Cite
The localization and regulation of proprotein convertase subtilisin/kexin (PCSK) 6 in human ovary Am J Reprod Immunol 2012;00:00–00, , , , , , , , , , .
- Issue published online: 8 NOV 2012
- Article first published online: 31 AUG 2012
- Manuscript Accepted: 9 JUL 2012
- Manuscript Received: 17 MAR 2012
- Bone morphogenetic protein;
- proprotein convertase;
- proprotein convertase subtilisin/kexin
The aim of this study is to evaluate the expression and regulation of proprotein convertase subtilisin/kexin (PCSK) 6, which is known to be an important factor in the production of bone morphogenetic protein (BMP) cytokines in human ovary.
Method of study
The localization of PCSK 6 protein in normal human ovaries was examined by immunohistochemistry. Human granulosa cells (GC), obtained from 34 patients undergoing ovarian stimulation for in vitro fertilization, were cultured with BMP-2, BMP-6, BMP-7, BMP-15, growth differentiation factor (GDF)-9, and activin-A with or without FSH. PCSK 6 mRNA expression level was evaluated by quantitative real-time reverse transcription and polymerase chain reaction (RT-PCR).
An immunohistochemistry study revealed that GC expressed PCSK 6 throughout follicular development, beginning in the primary follicle stage, while oocytes expressed PCSK 6 from the primordial follicle stage onwards. An in vitro study demonstrated that BMP-2, BMP-6, BMP-7, and BMP-15, not activin-A and GDF-9, decreased PCSK 6 gene expression in human GC. FSH induced PCSK 6 mRNA in the presence of activin-A or GDF-9. GDF-3, which is an inhibitor of BMP cytokines, also induced PCSK 6 mRNA expression.
PCSK 6, which is a critical factor to produce BMP cytokines, was suppressed with BMP stimulation in human GC, suggesting the presence of a negative feedback system in the follicular development process.