Estrogen Enhances Cystatin C Expression in the Macaque Vagina

Ov Slayden, Kevin Hettrich, Rebecca S. Carroll, Lesley N. Otto, Amanda L. Clark, Robert M. Brenner

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)883-891
    Number of pages9
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume89
    Issue number2
    DOIs
    StatePublished - Feb 2004

    Fingerprint

    Cystatin C
    Macaca
    Vagina
    Estrogens
    Muscle
    Animals
    Fibroblasts
    Smooth Muscle Myocytes
    In Situ Hybridization
    Immunohistochemistry
    Cells
    Hormones
    Cysteine Proteinase Inhibitors
    Pelvic Floor
    Cysteine Proteases
    Prolapse
    Anal Canal
    Menstrual Cycle
    Oligonucleotide Array Sequence Analysis
    Macaca mulatta

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Estrogen Enhances Cystatin C Expression in the Macaque Vagina. / Slayden, Ov; Hettrich, Kevin; Carroll, Rebecca S.; Otto, Lesley N.; Clark, Amanda L.; Brenner, Robert M.

    In: Journal of Clinical Endocrinology and Metabolism, Vol. 89, No. 2, 02.2004, p. 883-891.

    Research output: Contribution to journalArticle

    Slayden, Ov ; Hettrich, Kevin ; Carroll, Rebecca S. ; Otto, Lesley N. ; Clark, Amanda L. ; Brenner, Robert M. / Estrogen Enhances Cystatin C Expression in the Macaque Vagina. In: Journal of Clinical Endocrinology and Metabolism. 2004 ; Vol. 89, No. 2. pp. 883-891.
    @article{dd7a2506f9e4428f9c2b9bb9dfb31e36,
    title = "Estrogen Enhances Cystatin C Expression in the Macaque Vagina",
    abstract = "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.",
    author = "Ov Slayden and Kevin Hettrich and Carroll, {Rebecca S.} and Otto, {Lesley N.} and Clark, {Amanda L.} and Brenner, {Robert M.}",
    year = "2004",
    month = "2",
    doi = "10.1210/jc.2003-031143",
    language = "English (US)",
    volume = "89",
    pages = "883--891",
    journal = "Journal of Clinical Endocrinology and Metabolism",
    issn = "0021-972X",
    publisher = "The Endocrine Society",
    number = "2",

    }

    TY - JOUR

    T1 - Estrogen Enhances Cystatin C Expression in the Macaque Vagina

    AU - Slayden, Ov

    AU - Hettrich, Kevin

    AU - Carroll, Rebecca S.

    AU - Otto, Lesley N.

    AU - Clark, Amanda L.

    AU - Brenner, Robert M.

    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.

    UR - http://www.scopus.com/inward/record.url?scp=1442352195&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=1442352195&partnerID=8YFLogxK

    U2 - 10.1210/jc.2003-031143

    DO - 10.1210/jc.2003-031143

    M3 - Article

    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 -