TY - JOUR
T1 - Estrogen Enhances Cystatin C Expression in the Macaque Vagina
AU - Slayden, Ov D.
AU - Hettrich, Kevin
AU - Carroll, Rebecca S.
AU - Otto, Lesley N.
AU - Clark, Amanda L.
AU - Brenner, Robert M.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/2
Y1 - 2004/2
N2 - Cystatin C is a secreted inhibitor of cysteine proteinases that participates in extracellular matrix remodeling. Whether hormones affect its expression in the vagina was unknown. Consequently, we examined the effects of estradiol (E2), progesterone (P), and raloxifene on vaginal cystatin C in rhesus macaques. In experiment 1, ovariectomized animals were treated sequentially with E2 (14 d) and E2 + P (14 d) to induce 28-d menstrual cycles. Vaginal samples were collected on d 6, 8, 14, and 28 of the induced cycle. Some cycled animals were deprived of both E2 + P for 28 d. In experiment 2, ovariectomized animals were treated for 5 months with E2 alone, E2 + P, raloxifene, or left untreated. Total RNA from the vaginal wall was analyzed for the cystatin C transcript with a commercially prepared cDNA array and semiquantitative RT-PCR. Vaginal cryosections were analyzed by in situ hybridization for cystatin C transcript and by immunocytochemistry for the protein. E2 treatment significantly (5-fold; P < 0.05) increased expression of cystatin C transcript over the levels in the hormone-deprived controls, and cotreatment with P (E2 + P) blocked this effect. Raloxifene treatment did not affect cystatin C expression. In situ hybridization and immunocytochemistry revealed that cystatin C was localized in fibroblasts and smooth muscle cells throughout the vaginal wall but not in smooth muscle cells of arteries or levator ani myocytes. In summary, E2 increased vaginal cystatin C expression in the fibroblasts and smooth muscle bundles, P suppressed this effect, and raloxifene had no effects on cystatin C. Elevated cystatin C, by suppressing cysteine proteinase activity, may strengthen the vaginal wall and mitigate the potential for pelvic floor prolapse.
AB - Cystatin C is a secreted inhibitor of cysteine proteinases that participates in extracellular matrix remodeling. Whether hormones affect its expression in the vagina was unknown. Consequently, we examined the effects of estradiol (E2), progesterone (P), and raloxifene on vaginal cystatin C in rhesus macaques. In experiment 1, ovariectomized animals were treated sequentially with E2 (14 d) and E2 + P (14 d) to induce 28-d menstrual cycles. Vaginal samples were collected on d 6, 8, 14, and 28 of the induced cycle. Some cycled animals were deprived of both E2 + P for 28 d. In experiment 2, ovariectomized animals were treated for 5 months with E2 alone, E2 + P, raloxifene, or left untreated. Total RNA from the vaginal wall was analyzed for the cystatin C transcript with a commercially prepared cDNA array and semiquantitative RT-PCR. Vaginal cryosections were analyzed by in situ hybridization for cystatin C transcript and by immunocytochemistry for the protein. E2 treatment significantly (5-fold; P < 0.05) increased expression of cystatin C transcript over the levels in the hormone-deprived controls, and cotreatment with P (E2 + P) blocked this effect. Raloxifene treatment did not affect cystatin C expression. In situ hybridization and immunocytochemistry revealed that cystatin C was localized in fibroblasts and smooth muscle cells throughout the vaginal wall but not in smooth muscle cells of arteries or levator ani myocytes. In summary, E2 increased vaginal cystatin C expression in the fibroblasts and smooth muscle bundles, P suppressed this effect, and raloxifene had no effects on cystatin C. Elevated cystatin C, by suppressing cysteine proteinase activity, may strengthen the vaginal wall and mitigate the potential for pelvic floor prolapse.
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U2 - 10.1210/jc.2003-031143
DO - 10.1210/jc.2003-031143
M3 - Article
C2 - 14764809
AN - SCOPUS:1442352195
VL - 89
SP - 883
EP - 891
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 2
ER -