Relaxin Acts on Stromal Cells to Promote Epithelial and Stromal Proliferation and Inhibit Apoptosis in the Mouse Cervix and Vagina

• Published in: Endocrinology (Philadelphia) 2008-05, Vol.149 (5), p.2072-2079
• Main Authors: Yao, LiJuan, Agoulnik, Alexander I, Cooke, Paul S, Meling, Daryl D, Sherwood, O. David
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Algorithms; Animals; Animals, Newborn; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cell Lineage; Cell proliferation; Cell Proliferation - drug effects; Cervix; Cervix Uteri - drug effects; Cervix Uteri - metabolism; DNA nucleotidylexotransferase; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelium; Female; Fundamental and applied biological sciences. Psychology; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Kidney transplantation; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Ovariectomy; Progesterone; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Recombinants; Relaxin; Relaxin - pharmacology; Relaxin - physiology; Sex hormones; Stromal cells; Stromal Cells - drug effects; Stromal Cells - metabolism; Syngeneic grafts; Transplants & implants; Vagina; Vagina - drug effects; Vagina - metabolism; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2007-1176

The objective of this study was to determine whether stromal and/or epithelial relaxin receptor (LGR7) is required for relaxin to promote proliferation and inhibit apoptosis of stromal and epithelial cells in the mouse cervix and vagina. Tissue recombinants were prepared with stroma (St) and epithelium (Ep) from wild-type (wt) and LGR7 knockout (ko) mice: wt-St+wt-Ep, wt-St+ko-Ep, ko-St+wt-Ep, and ko-St+ko-Ep. Tissue recombinants were grafted under the renal capsule of intact syngeneic female mice. After 3 wk of transplant growth, hosts were ovariectomized and fitted with silicon implants containing progesterone and estradiol-17β (designated d 1 of treatment). Animals were injected sc with relaxin or relaxin vehicle PBS at 6-h intervals from 0600 h on d 8 through 0600 h on d 10 of treatment. To evaluate cell proliferation, 5-bromo-2′-deoxyuridine was injected sc 10 h before cervices and vaginas were collected at 1000 h on d 10. Terminal deoxynucleotidyl transferase-mediated deoxyuridine 5′-triphosphate nick end labeling was used to quantify apoptosis. Relaxin markedly increased proliferation and decreased apoptosis of epithelial and stromal cells in tissue recombinants containing wt stroma (P < 0.01) but had no effect on tissue recombinants prepared with ko stroma, regardless of whether epithelium was derived from wt or ko mice. In conclusion, this study shows that LGR7-expressing cells in the stroma are both necessary and sufficient for relaxin to promote proliferation and inhibit apoptosis in both stromal and epithelial cells of cervix and vagina, whereas epithelial LGR7 does not affect these processes.