In Vitro Evidence Suggests Activin-a May Promote Tissue Remodeling Associated with Human Luteolysis.
From: Obstetrics and Gynaecology, Department of Reproductive and Developmental Sciences, University of Edinburgh, United Kingdom. m.myers@sms.ed.ac.uk
Endocrinology
- Publish Date: Aug 2007
- ISSN: 0013-7227
- Volume: 148
- Issue: 8
- Pages: 3730-9
- Medium: Print
- Language: English
- Citation (JAMA): Myers Michelle, Gay Eva, McNeilly Alan S, et al. In Vitro Evidence Suggests Activin-a May Promote Tissue Remodeling Associated with Human Luteolysis.. Endocrinology Aug 2007;148:3730-9
Abstract
Luteolysis in women is associated with an up-regulation of the expression and activity of matrix metalloproteinase-2 (MMP-2), which is inhibited by human chorionic gonadotropin (hCG) during maternal recognition of pregnancy. Because the primary source of MMP-2 is fibroblasts that do not express LH/hCG receptors, we aimed to investigate the regulation of MMP-2. Women with regular cycles having hysterectomy for nonmalignant conditions and women undergoing oocyte retrieval for assisted conception were used in this current study. Novel primary cultures and cocultures of luteinized granulosa cells and fibroblast-like cells in conjunction with human corpora lutea from different stages of the luteal phase were used to investigate the role of activin-A in the corpus luteum. The effect of hCG, activin-A, and follistatin on MMP-2 activity and expression was assessed by gelatin zymography and quantitative RT-PCR in primary cell cultures. Confirmation of signaling pathways involved in the activation of MMP-2 was assessed by immunofluorescence, RT-PCR, and quantitative RT-PCR. In primary cell culture, steroidogenic cells secrete activin-A and its inhibitors, inhibin-A and follistatin. Follistatin expression is up-regulated by hCG (P < 0.05). The fibroblast-like cells producing MMP-2 have the machinery for activin reception, expressing both type I and type II activin receptors and Smad proteins. Activin-A up-regulated both activity and expression of MMP-2 in fibroblast-like cells (P < 0.05). This activity was inhibited in cocultures of luteinized granulosa cells and fibroblast-like cells in the presence of hCG (P < 0.05) or follistatin (P < 0.01). Activin-A is an excellent candidate for an effector molecule in human luteolysis whose paracrine action is inhibited during maternal recognition of pregnancy.
Mesh Headings (Keywords): Activins, Cells, Cultured, Chorionic Gonadotropin, Corpus Luteum, Female, Fibroblasts, Follistatin, Granulosa Cells, Humans, Inhibins, Luteal Phase, Luteolysis, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Paracrine Communication, RNA, Messenger, Signal Transduction, Smad2 Protein, Smad3 Protein
Check for Full Text / PubMed Unique Identifier (PMID): 17478557
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