HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0302v1 199/2/201    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Myers, M. Articles by Duncan, W. Search for Related Content PubMed PubMed Citation Articles by Myers, M. Articles by Duncan, W.

M Myers, Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh, United Kingdom
S van den Driesche, Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh, United Kingdom
A McNeilly, MRC Human Reproductive Sciences Unit, Edinburgh, United Kingdom
W Duncan, Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh, EH16 4SA, United Kingdom

Correspondence: William Duncan, Email: W.C.Duncan{at}ed.ac.uk

Abstract

The transition of the dominant follicle in the corpus luteum is of fundamental reproductive importance. Luteinisation involves disparate changes in the gene expression of follicular granulosa cells which differentiate into the granulosa-lutein cells of the corpus luteum after the gonadotrophin surge. We have shown that activin and hCG have opposing effects during luteolysis. Therefore we hypothesised that activin A was an inhibitor of luteinisation that was blocked during the preovulatory 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, whilst activin A promotes a more follicular phenotype in luteinised cells by up-regulating granulosa cells markers such as FSHR, HSD11B2 and down-regulating LHCGR. In addition activin A blocked hCG up-regulation of STAR, HSD3B1 and HSD11B1 and down-regulation of ESR1. Activin A antagonised hCG effects in a dose-dependent manner and could block the hCG stimulated molecular inhibitors of activin action (INHA, FST and TGFBR3). These studies show that hCG and activin A have opposing effects on luteinised granulosa cells and some effects of activin are only seen 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.

This article has been cited by other articles:

				Y. Xia and A. L Schneyer The biology of activin: recent advances in structure, regulation and function J. Endocrinol., July 1, 2009; 202(1): 1 - 12. [Abstract] [Full Text] [PDF]