[Multiple blue nevi of the vagina--a rare differential diagnosis to melanoma of the vagina].
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Recently, it was demonstrated that endogenous relaxin promotes growth of the vagina during the second half of pregnancy in rats and that administration of porcine relaxin promotes growth of the uterus in nonpregnant or early pregnant gilts. This study examined the effects of circulating relaxin on growth of both the vagina and uterus during the last two thirds of the 114-day gestation period in gilts. Furthermore, this study employed an in vitro immunohistochemical localization technique to determine whether the vagina and uterus in pigs have specific relaxin-binding sites. Three groups of pregnant gilts were used: sham-ovariectomized controls (group C; n = 8), ovariectomized progesterone-treated (group OP; n = 6), and ovariectomized progesterone- plus relaxin-treated (group OPR; n = 7). Gilts were either sham ovariectomized or ovariectomized on day 40 of gestation. Hormone replacement therapy with progesterone (group OP), progesterone plus relaxin (group OPR), or hormone vehicles (group C) began on day 38 (progesterone) or day 40 (relaxin) and continued until day 110. On day 110, the vagina and uterus were collected, and wet weight, dry weight, and percent hydration were determined. Small pieces (2-3 cm3) of the vagina and uterus from groups C and OP were frozen and cryosectioned for the immunohistochemical localization of relaxin-binding sites. Relaxin promoted growth of both the vagina and uterus. The wet weights of both the vagina and uterus in relaxin-deficient gilts (group OP) were lower (P < 0.05) than those in controls (group C), and relaxin replacement therapy (group OPR) restored the wet weights of both tissues to values that did not differ from those in controls. The mean dry weights and percent hydrations in the vagina and uterus did not differ among treatments. Immunohistochemical localization studies in the vagina and uterus demonstrated that specific and saturable binding of relaxin was localized in the same cell types of both tissues, namely epithelial cells (luminal in vagina, and both luminal and glandular in uterus), smooth muscle cells (both circular and longitudinal in vagina, and myometrial in uterus), and cells associated with blood vessels. In conclusion, this study provides evidence that circulating relaxin promotes growth of both the vagina and uterus during pregnancy in the pig. Furthermore, this study provides evidence that both the vagina and uterus contain specific and saturable relaxin-binding sites in epithelial cells, smooth muscle cells, and cells associated with blood vessels. We conclude that these cells probably initiate relaxin's effects on the vagina and uterus of the pregnant pig.
Nitric oxide synthase (NOS) and arginase have been shown to regulate nitric oxide (NO) production reciprocally in genital tissues. In animal models, NO is an important regulator of vaginal blood flow and vaginal wall contractility. In this study, we investigated the modulation of NOS and arginase activities by estrogens and androgens in the proximal and distal rabbit vagina. In intact control animals, total NOS activity was higher in the proximal (528+/-78 pmol/mg protein) than the distal (391+/-44 pmol/mg protein) vagina. However, arginase activity was higher in the distal (206+/-8 nmol/mg protein) than the proximal (64+/-5 nmol/mg protein) vagina. Ovariectomy enhanced NOS activity in the proximal but not distal vagina with concomitant decrease in arginase activity in both the proximal and distal vagina. In ovariectomized rabbits, replacement with 5alpha-dihydrotestosterone (DHT) or Delta5-androstenediol (Adiol) increased NOS activity beyond that observed in ovariectomized rabbits receiving vehicle. In contrast, DHT and Adiol treatment reduced arginase activity more than that of the ovariectomized rabbits receiving vehicle. Testosterone exhibited inconsistent effects on NOS and arginase activity in the distal and proximal vagina. Estradiol replacement in ovariectomized animals reduced NOS activity in the proximal vagina down to levels that were comparable to intact control animals. However, estradiol positively modulated arginase activity in the distal vagina. Western blot analyses indicated that in the proximal vagina, neural NOS protein levels paralleled the changes observed in enzyme activity. These observations suggest that steroid hormones differentially regulate NOS and arginase activities of the proximal and distal regions of the vagina. Although estrogen treatment reduced total NOS activity in proximal vagina, estrogens are known to enhance vaginal blood flow. This paradoxical observation may be explained by differential regulation of n-NOS and e-NOS in the proximal and distal vagina. We suggest that changes in vaginal blood flow and compliance may depend on the endocrine status and the levels of circulating androgens and estrogens.
Perinatal treatment of female mice with natural or synthetic estrogens including diethylstilbestrol (DES) results in estrogen-independent persistent proliferation and cornification of the vaginal epithelium. However, the molecular mechanisms of the estrogen-independent changes have not been elucidated. To analyze the mechanism of estrogen-independent cell proliferation and cornification of the vaginal epithelium, we used differential display and determined specific genes expressed in neonatally DES-treated vagina. A candidate clone that designated DDV5 was identical to the serine protease, neuropsin that is reportedly expressed in the mouse central nervous system. We then analyzed the expression pattern of DDV5/neuropsin using Northern blot analysis. We found: (1). DDV5/neuropsin mRNA is expressed in vaginae from neonatally DES-treated ovariectomized mice but not in vaginae from ovariectomized control mice, (2). its expression is not detected in uteri from neonatally DES-treated mice, (3). DDV5/neuropsin is expressed in vaginae from normal intact mice during estrus. Furthermore, we found that DDV5/neuropsin mRNA rapidly decreased in vaginae after ovariectomy. DDV5/neuropsin was detected in vaginae from ovariectomized mice 48 h after estrogen treatment. These results suggest that DDV5/neuropsin is expressed in estrogen-stimulated mouse vagina, and its gene expression is regulated by estrogen. Neonatal DES exposure affects transcriptional control of DDV5/neuropsin in the mouse vagina, which results in persistent expression of DDV5/neuropsin even after ovariectomy, thus, DDV5/neuropsin may play a role in estrogen-independent persistent proliferation and cornification of the vaginal epithelium. Using in situ hybridization method, we found DDV5/neuropsin mRNA localized in epithelial cells but not stromal cells in vaginae. This is the first report on the gene expression of a serine-protease neuropsin in the mouse vagina, and as a marker of the estrogen-independent persistent proliferation and cornification of the vaginal epithelium.