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Biomedical subjects

R R Greb

Publications and source records attributed to R R Greb.

5 recordsLinked to original sources
PubMed2000

Localization in tissues and secretion of eotaxin by cells from normal endometrium and endometriosis.

Our laboratories have focused recently on the production and localization of eotaxin, a C-C-chemokine of 8.4 kDa, whose major biological activity is the chemoattraction of eosinophils. Given evidence of autoimmune activity in the endometriosis syndrome, we hypothesized that eosinophil chemoattractants might be expressed in endometriosis. In histological sections, we observed eotaxin protein localized mainly in epithelial cells, with only very faint immunostaining in the surrounding stromal cells. Prominent eotaxin accumulation was noted in the luminal epithelium of secretory endometrium. Eotaxin distribution in endometriosis was similar to that seen in eutopic endometrium but with higher levels of eotaxin staining in the glandular epithelium. Peritoneal fluid concentrations of eotaxin were significantly higher in women with moderate or severe endometriosis than in women with minimal or mild endometriosis or no disease. The treatment of isolated human endometriosis epithelial cells with estradiol, medroxyprogesterone acetate, tumor necrosis factor-alpha, and interferon-gamma stimulated measurable eotaxin secretion into the conditioned media. The results indicate that eotaxin is produced in epithelial cells of normal endometrium and endometriosis tissues, varies across the menstrual cycle, and is elevated in women with endometriosis. We postulate that eotaxin, interacting with other known cytokines and immune cells, contributes to an inflammatory reproductive tract environment, leading to endometrial or blastocyst dysfunction.

Adult↗
PubMed1999

Vascular endothelial growth factor A (VEGF-A) mRNA expression levels decrease after menopause in normal breast tissue but not in breast cancer lesions.

We hypothesized that the regulation of microvascular functions and angiogenesis in breast tissue, a well known target of ovarian steroid action, is dependent on the hormonal exposure of the breast. Relative expression levels of VEGF-A (vascular endothelial growth factor A), a putative key regulator of angiogenesis in breast cancer, were analysed in the tumour and the adjacent non-neoplastic breast tissue of 19 breast cancer patients by quantitative reverse transcriptase polymerase chain reaction. In non-neoplastic breast specimens the expression levels of all detected VEGF-A-isoforms (189, 165, 121) were significantly higher in premenopausal compared to post-menopausal women (P = 0.02) and were inversely correlated with the patient's age (P = 0.006). In contrast, in cancerous tissues menopausal status had no influence on VEGF-A-expression levels. Benign and malignant tissues exhibited a similar expression pattern of VEGF-A-isoforms relative to each other. Thus, the regulation of the vasculature in normal breast tissue, as opposed to breast cancer tissue, appears to be hormonally dependent. Endogenous and therapeutically used hormonal steroids might, therefore, cause clinically relevant changes of the angiogenic phenotype of the human breast.

Adult↗
PubMed1999

Disparate actions of mifepristone (RU 486) on glands and stroma in the primate endometrium.

Besides being an antiprogestin, mifepristone (RU 486) was recently shown to antagonize oestrogen-dependent growth in the endometrium. To explore the molecular mechanisms for this phenomenon, we investigated whether or not the morphological effects of mifepristone are mediated by the progesterone receptor (PR) and whether mifepristone has disparate effects on the glandular epithelium and stroma. Six groups of hypogonadal, oestrogen-primed cynomolgus monkeys were treated for 2 weeks with: vehicle only (group I); mifepristone (group II); mifepristone plus progesterone at 0.2 mg/kg (group III), 1.0 mg/kg (group IV) or 5.0 mg/kg (group V); and progesterone only (5.0 mg/kg) (group VI). Histomorphological evaluation showed strikingly compacted stroma in the mifepristone-exposed endometria (group II), which was partially reversible by additional progesterone treatment (groups III-V). Glandular proliferation (pseudostratification, glandular mitoses) in mifepristone-treated monkeys was not significantly different from that in vehicle (oestradiol)-treated monkeys, but was inhibited by progesterone-only treatment. Cells containing vacuoles were scarce in the mifepristone-exposed endometrium, but detected frequently in progesterone-exposed endometria, indicating the strong antisecretory effect of mifepristone on glands. We conclude that oestrogen-dependent oedema in the stroma is antagonized by mifepristone. The reversal of this effect by progesterone suggests a PR-mediated mechanism. In glands, mifepristone is antiprogestogenic, but not antioestrogenic. Thus, stromal cells may be the target of antiprogestin-induced inhibition of oedema and endometrial growth.

Animals↗
PubMed1997

Vascular endothelial growth factor in primate endometrium is regulated by oestrogen-receptor and progesterone-receptor ligands in vivo.

We investigated hormonal regulation of endometrial angiogenesis in menstruating primates. This study was designed to demonstrate: (i) that cell-specific vascular endothelial growth factor (VEGF) production and expression in monkey endometrium are regulated by steroid receptor ligands; and (ii) mifepristone (RU 486) alters VEGF production even in the absence of a progestin agonist. Endometrial VEGF production was compared by computer-assisted immunohistochemical analysis during induced hypoestrogenism and after oestradiol, progestin, or antiprogestin (mifepristone) treatment. VEGF gene expression was estimated by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in endometrial samples from castrate cynomolgus monkeys, from intact monkeys in the luteal phase, and from monkeys treated for 20 days with levonorgestrel (LNG) or mifepristone. VEGF staining intensities in glandular epithelium and VEGF mRNA expression were highest in hypoestrogenic monkeys. Progestin treatment induced intense VEGF staining in the stroma. Gene expression of VEGF-189, but not other isoforms, was higher in progesterone- and progestin (LNG)-exposed endometria compared to mifepristone-exposed endometria or endometria from anovulatory cycles (P < 0.04). Mifepristone abolished VEGF staining in glandular epithelium almost completely. We conclude that VEGF protein and VEGF mRNA expression levels in primate endometrium depend on the steroidal milieu. Anti-angiogenic effects of mifepristone via suppression of VEGF production might represent a mechanism for its quelling effects on endometrium.

Animals↗