We describe a series of women after allogeneic stem cell transplantation with vaginal graft-versus-host disease (GVHD) who were treated with topical cyclosporine, surgery, or both. We reviewed the medical charts of 11 women who presented with vaginal pain, discomfort, and vaginal scarring (inability to perform a Papanicolaou test or have vaginal intercourse because of pain). Vaginal symptoms develop an average of 10 months from bone marrow transplantation. Symptoms and physical findings include excoriated and ulcerated mucosa, thickened mucosa, narrowed introitus, and obliterated introitus from dense scar tissue that does not resolve with systemic or topical estrogens. The severity of symptoms and the physical findings in our study population did not correlate with age, type of leukemia, type of transplant, or severity or acute or chronic GVHD. Excoriated mucosa and moderately thickened mucosa were successfully treated with topical cyclosporine. Extensive synechiae and complete obliteration of the vaginal canal required surgical lysis with postoperative topical cyclosporine. Vaginal GVHD can successfully be treated with topical cyclosporine when mild to moderate disease is present. Surgical lysis with topical cyclosporine is required when more severe disease ensues.

The response of pituitary gonadotropes to gonadotropin-releasing hormone (GnRH) correlates directly with the concentration of GnRH receptors (GnRHR) on the cell surface, which is mediated in part at the level of gene expression. Several factors are known to affect expression of the mouse GnRHR (mGnRHR) gene, including GnRH and activin. We have previously shown that activin augments GnRH-mediated transcriptional activation of mGnRHR gene, and that region ؊387/؊308 appears to be necessary to mediate this effect. This region contains two overlapping cis-regulatory elements of interest: GnRHR activating sequence (GRAS) and a putative SMAD-binding element (SBE). This study investigates the role of these elements and their cognate transcription factors in transactivation of the mGnRHR gene. Transfection studies confirm the presence of GnRH-and activin-response elements within ؊387/؊308 of mGnRHR gene promoter. Competition electrophoretic mobility shift assay experiments using ؊335/ ؊312 as probe and ␣T3-1 nuclear extract or SMAD, Jun, and Fos proteins demonstrate direct binding of AP-1 (Fos/Jun) protein complexes to ؊327/؊322 and SMAD proteins to ؊329/؊328. Further transfection studies using mutant constructs of these cis-regulatory elements confirm that both are functionally important. These data define a novel cis-regulatory element comprised of an overlapping SBE and newly characterized non-consensus AP-1 binding sequence that integrates the stimulatory transcriptional effects of both GnRH and activin on the mGnRHR gene.