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Response of matrix metalloproteinases and tissue inhibitors of metalloproteinases messenger ribonucleic acids to ovarian steroids in human endometrial explants mimics their gene- and phase-specific differential control in vivo.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2005 Oct; Vol. 90 (10), pp. 5848-57. Date of Electronic Publication: 2005 Jul 26. - Publication Year :
- 2005
-
Abstract
- Context: Cyclic remodeling and breakdown of the extracellular matrix, a unique feature of the human endometrium, depends on matrix metalloproteinases (MMPs). These enzymes are globally controlled by estradiol and progesterone or their withdrawal, but various MMPs and their tissue inhibitors (TIMPs) show distinct responses.<br />Objective and Design: To clarify the role of ovarian steroids in the differential regulation of MMP-1, MMP-3, MMP-7, MMP-8, MMP-10, TIMP-1, TIMP-2, and TIMP-3 mRNAs, we compared their variations in the cycling endometrium in vivo with their response to hormone addition or withdrawal in corresponding explants.<br />Results: Different patterns were identified in vivo according to the time frame (secretory vs. perimenstrual increase), sharpness (peak vs. progressive increase or decrease), and magnitude of the changes. In vivo ratios between early/midsecretory and perimenstrual phases ranged from more than 1000 (MMP-1, MMP-3, and MMP-10) to less than 10 (TIMPs). Differential response to ovarian steroids of the various MMPs and TIMPs mRNAs tested in cultured explants matched the same ranking and varied according to the phase at sampling. Remarkably, ovarian steroids repressed MMPs and TIMP-1 and TIMP-2 but, in secretory explants, increased TIMP-3 mRNA. Finally, in situ hybridization evidenced the major contribution of fibroblasts to the increase in MMP-8 mRNA at menstruation or in explants cultured without hormones.<br />Conclusions: Both phase- and gene-specific modulators finely tune in space, time, and amplitude the global control of MMPs and TIMPs mRNAs by estradiol and progesterone in the cycling human endometrium.
- Subjects :
- Adult
Endometrium drug effects
Estradiol pharmacology
Female
Fibroblasts drug effects
Fibroblasts metabolism
Humans
Immunoblotting
In Situ Hybridization
Matrix Metalloproteinases biosynthesis
Menstrual Cycle physiology
Middle Aged
Ovary drug effects
Progesterone pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Tissue Culture Techniques
Tissue Inhibitor of Metalloproteinases biosynthesis
Endometrium metabolism
Gonadal Steroid Hormones pharmacology
Matrix Metalloproteinases genetics
Ovary physiology
RNA, Messenger biosynthesis
Tissue Inhibitor of Metalloproteinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0021-972X
- Volume :
- 90
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 16046583
- Full Text :
- https://doi.org/10.1210/jc.2005-0762