• Made available online as an Accepted Preprint 18 August 2008
  • Accepted Preprint first posted online on 18 August 2008

Activin A reduces luteinisation of human luteinised granulosa cells and has opposing effects to human chorionic gonadotropin in vitro

  1. W Colin Duncan
  1. Obstetrics and Gynaecology, Department of Reproductive and Developmental Sciences, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK1MRC Human Reproductive Sciences Unit, Queen's Institute of Medical Research, Centre for Reproductive Biology, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
  1. (Correspondence should be addressed to W C Duncan at Obstetrics and Gynaecology, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK; Email: w.c.duncan{at}ed.ac.uk)


The transition of the dominant follicle into the corpus luteum is of fundamental reproductive importance. Luteinisation involves disparate changes in the gene expression of follicular granulosa cells that differentiate into the granulosa-lutein cells of the corpus luteum after the gonadotrophin surge. We have shown that activin and human chorionic gonadotropin (hCG) have opposing effects during luteolysis. Therefore, we hypothesised that activin A was an inhibitor of luteinisation that was blocked during the pre–ovulatory gonadotrophin surge. Ovarian tissue and cells were collected from women with regular cycles having hysterectomy and women undergoing oocyte retrieval for assisted conception. Genes that changes during luteinisation were investigated in primary cultures of luteinised granulosa cells exposed to activin A and hCG in vitro. hCG promotes a luteinised granulosa cell phenotype, while activin A promotes a more follicular phenotype in luteinised cells by upregulating granulosa cells markers such as FSHR, HSD11B2 and downregulating LHCGR. In addition, activin A blocked hCG upregulation of STAR, HSD3B1 and HSD11B1 and downregulation of oestrogen receptor α. Activin A antagonised hCG effects in a dose-dependent manner and could block the hCG-stimulated molecular inhibitors of activin action (inhibin α-subunit, follistatin and TGFBR3). These studies show that hCG and activin A have opposing effects on luteinised granulosa cells and some effects of activin are seen only in the presence of hCG. While hCG can inhibit activin action in granulosa cells to facilitate luteinisation, activin A can promote an unluteinised phenotype in luteinised granulosa cells. This confirms the importance of adequate activin withdrawal during luteinisation in women.

  • Received in final form 28 July 2008
  • Accepted 7 August 2008
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