Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tibolone, a tissue-selective compound with a combination of estrogenic, progestagenic, and androgenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. The current study compares the endometrial gene expression profiles after short-term (21 days) treatment with tibolone to the profiles after treatment with estradiol-only (E(2)) and E(2) + medroxyprogesterone acetate (E(2) + MPA) in healthy postmenopausal women undergoing hysterectomy for endometrial prolapse. The impact of E(2) treatment on endometrial gene expression (799 genes) was much higher than the effect of tibolone (173 genes) or E(2) + MPA treatment (174 genes). Furthermore, endometrial gene expression profiles after tibolone treatment show a weak similarity to the profiles after E(2) treatment (overlap 72 genes) and even less profile similarity to E(2) + MPA treatment (overlap 17 genes). Interestingly, 95 tibolone-specific genes were identified. Translation of profile similarity into biological processes and pathways showed that ER-mediated downstream processes, such as cell cycle and cell proliferation, are not affected by E2 + MPA, slightly by tibolone, but are significantly affected by E(2). In conclusion, tibolone treatment results in a tibolone-specific gene expression profile in the human endometrium, which shares only limited resemblance to E(2) and even less resemblance to E2 + MPA induced profiles.
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PMID:Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling. 1722 44

Progesterone and progesterone receptors (PGR) are known to play important roles in the pathophysiology of pelvic organ prolapse (POP). We investigated whether the PGR gene polymorphisms were associated with POP by conducting a case-control association study in 87 women with POP and 150 women without POP. Genotypes of the PGR gene polymorphisms (rs500760 and rs484389) were determined by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. There was significant difference between women with and those without POP in the distribution of the PGR rs484389 genotypes evaluated. Using multivariable logistic regression, older age, increased body mass index, menopausal status, and PGR rs484389 genotype CT were significantly associated with POP. The present study shows that PGR genotype may be associated with POP.
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PMID:Progesterone receptor polymorphism is associated with pelvic organ prolapse risk. 1926 71

Foxl2 codes for a forkhead/HNF3 transcription factor essential for follicular maturation and maintenance of ovarian identity. FOXL2 mutations are associated with Blepharophimosis, Ptosis and Epicanthus inversus Syndrome (BPES) characterized by eyelid malformations (types I and II) and premature ovarian insufficiency (type I). We show that Foxl2 is not only expressed by the ovary, but also by other components of the mouse female reproductive tract, including the uterus, the cervix and the oviduct. In the uterus, Foxl2 expression is first observed in the neonatal mesenchyme and, during uterine maturation, persists in the stroma and in the deep inner myometrial layer (IML). In the adult, Foxl2 is expressed in the differentiated stromal layer, but no longer in the myometrium. Conditional deletion of Foxl2 in the postnatal (PN) uterus using Progesterone Receptor-cre (Pgr(cre/+)) mice results in infertility. During PN uterine maturation Pgr(cre/+); Foxl2(flox/flox) mice present a severely reduced thickness of the stroma layer and an hypertrophic, disorganized IML. In adult Pgr(cre/+); Foxl2(flox/flox) mice a supplementary muscular layer is present at the stroma/myometrium border and vascular smooth muscle cells fail to form a coherent layer around uterine arteries. Wnt signalling pathways play a central role in uterine maturation; in Pgr(cre/+); Foxl2(flox/flox) mice, Wnt genes are deregulated suggesting that Foxl2 acts through these signals. In humans, thickening of the IML (also called "junctional zone") is associated with reduced fertility, endometriosis and adenomyosis. Our data suggest that Foxl2 has a crucial role in PN uterine maturation and could help to understand sub-fertility predisposition in women.
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PMID:Role of Foxl2 in uterine maturation and function. 2568 38

This study investigated whether ovariohysterectomy (OVH) surgery to induce menopause resulted in changes to modulus, failure strain and lubricin/proteoglycan 4 (PRG4) gene expression in rabbit medial collateral ligaments (MCLs), similar to aging (Thornton et al., 2015a). The MCLs from adult rabbits that underwent OVH surgery as adolescents (15-week-old) and adults (1-year-old) were compared by evaluating mechanical behaviour (adolescent OVH, n=8; adult OVH, n=7; normal, n=7), gene expression (adolescent OVH, n=9; adult OVH, n=8; normal, n=8), and collagen and glycosaminoglycan (adolescent OVH, n=9; adult OVH, n=8; normal, n=8) and water (adolescent OVH, n=9; adult OVH, n=8; normal, n=8) content. Mechanical behaviour evaluated cyclic, static and total creep strain, and ultimate tensile strength, modulus and failure strain. The RT-qPCR assessed mRNA levels for matrix regulatory genes. Adult OVH MCLs exhibited increased cyclic creep and failure strain, and decreased modulus with increased mRNA levels for lubricin/PRG4 and collagen I compared with normal MCLs. Adolescent OVH MCLs exhibited increased cyclic, static and total creep strain with decreased mRNA levels for the progesterone receptor. Lubricin/PRG4 plays a role in the lubrication of collagen fascicles which is likely related to the decreased modulus and increased failure strain observed in ligaments from adult OVH rabbits. Progesterone and its receptor are thought to play a role in the stretching of ligaments in pelvic organ prolapse and pregnancy which is likely related to the increase in creep strain observed in ligaments from adolescent OVH rabbits. Ovariohysterectomy in adult rabbits resulted in changes that were consistent with the aging MCL.
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PMID:Increased lubricin/proteoglycan 4 gene expression and decreased modulus in medial collateral ligaments following ovariohysterectomy in the adult rabbit: Evidence consistent with aging. 2677 33