Anti-Mullerian hormone signaling is influenced by Follistatin 288, but not 14 other transforming growth factor beta superfamily regulators

作者：Kawagishi Yui; Pankhurst Michael W; Nakatani Yoshio; McLennan Ian S^*

来源：Molecular Reproduction and Development, 2017, 84(7): 626-637.

DOI：10.1002/mrd.22828

• cytokine
• dose-response curve
• EC50

The hypothesis that, in contrast to other transforming growth factor-beta (TGF beta) superfamily ligands, the dose-response curve of Anti-Mullerian hormone (AMH) is unmodulated was tested by examining whether known TGFB superfamily modulators affect AMH signaling, using a P19/BRE luciferase reporter assay. AMH(C) and AMH(N,C) activated the reporter with an EC50 of approximately 0.5 nM. Follistatins (FS) produced concentration-dependent increases in AMH(C)- and AMH(N,C)-initiated reporter activity, with FS288 being more potent than FS315; however, the maximum bioactivity of AMH was not altered by either follistatin. Thirteen other TGF beta regulators (Chordin, Chordin-like 1, Chordin-like 2, Differential screening-selected gene aberrative in neuroblastoma [DAN], Decorin, Endoglin, Follistatin-like 1, Follistatin-like 3, Follistatin-like 4, Noggin, alpha 2 macroglobulin, TGF beta receptor 3, Von Willebrand factor C domain-containing 2) had little or no effect. Surface plasmon resonance analysis showed no significant association between FS288 and AMH(C), suggesting that FS288 indirectly regulates AMH signaling. Activin A, a direct target of FS288, did not itself induce reporter activity in P19 cells, but did prevent the FS288-induced increase in AMH signaling. Hence, local concentrations of FS288 and Activin A may influence the response of some cell types to AMH.

• 出版日期2017-7