Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ovarian steroids are associated with the proliferation of normal as well as tumorigenically transformed mammary epithelial cells. The experiments performed in this study were designed to establish that (1) tumorigenic transformation induced by the ras oncogene is associated with alterations in estradiol biotransformation, (2) altered endocrine responsiveness persists in the fully transformed tumor cell phenotype and (3) specific perturbations induced by the ras oncogene can be experimentally downregulated. The ras transfectant pH06T and the tumor-derived T1/Pr1 cells exhibited 3- and 43-fold increases, respectively, in C-16 alpha hydroxylation of estradiol relative to the parental mouse mammary epithelial cells (P less than 0.0001). At the cellular level, this alteration corresponded with approximately 90-fold increase in the anchorage-independent growth of T1/Pr1 cells (P less than 0.0001). Estrogen responsiveness of T1/Pr1 cells was demonstrated by their suppression of growth in phenol red-free and/or tamoxifen-supplemented medium and by the reversal of antiproliferative effect of tamoxifen by phenol red and estradiol. Indole-3-carbinol, a naturally occurring tumor suppressive agent, was able to upregulate C-2 hydroxylation at the expense of C-16 alpha hydroxylation of estradiol. Treatment of T1/Pr1 cells with indole-3-carbinol resulted in a substantial decrease in anchorage-independent growth.
Steroids 1992 Jun
PMID:Persistent estrogen responsiveness of ras oncogene-transformed mouse mammary epithelial cells. 144 Jun 96

In each menstrual cycle only very few follicles in the mammalian ovary undergo maturation and ovulation while most of the follicles degenerate in the process of atresia. Moreover, in the absence of pregnancy, the newly formed corpora lutea will degenerate and disappear in the process of luteolysis. Recent studies suggest that ovarian follicular atresia is associated with DNA fragmentation and degeneration of follicular cells, characteristics of programmed cell death (apoptosis). Apoptosis can be induced in vitro, in primary granulosa cell culture, by serum deprivation and by induction of a high intracellular level of cAMP. This induction of apoptosis can be blocked by fibroblast growth factor, suggesting that receptor-medicated activation of a tyrosine kinase can serve as a survival signal. Apoptosis can also be induced in immortalized steroidogenic granulosa cells, transformed by SV40 DNA and Ha-ras oncogene, by overexpression of the wild-type p53 tumor suppressor gene in cAMP-stimulated cells. Omitting the cAMP stimulus prevents the p53-induced apoptosis in these cells, suggesting cross-talk between p53 and c-AMP-generated signals in the induction of apoptosis. Steroidogenic activity in these cells, as well as in nontransformed granulosa cells, does not decline during apoptosis but is rather significantly elevated before total cell collapse occurs. Cytochemical studies using confocal laser microscopy, electron microscopy, and three-dimensional reconstruction reveal a specific reorganization pattern of proteasomes, the most abundant nonlysosomal protease, and of the steroidogenic organelles, such as mitochondria and lipid droplets, in the apoptotic cell. Our results suggest that compartmentalization of intracellular organelles during apoptosis permits proteolysis without interfering with steroidogenesis, characteristic of the differentiated phenotype of the granulosa cell. Moreover, cytoskeletal rearrangement may serve as a barrier between these cellular activities.
Steroids 1996 Apr
PMID:Cross-talk between cAMP and p53-generated signals in induction of differentiation and apoptosis in steroidogenic granulosa cells. 873 10

Expression of the ras family of cellular oncogenes is associated with tumorigenicity, invasiveness and metastatic potential in a variety of human carcinomas. Additionally, H-ras cooperates with glucocorticoids and with ovarian hormones in cell transformation and in the development of mammary carcinomas. Steroids are considered to be tumor promoters and their levels influence the cure rates and survival of the patients with gynecological lesions. It is proposed that they exert tumor promoting activity by transcriptional regulation of nuclear proto-oncogenes, such as c-fos, c-jun, and c-myc. The human H-ras gene contains within its first and fourth introns, sequences that are specifically recognized by glucocorticoid and estrogen receptors, respectively. Using gel retardation assays, the level of steroid receptor binding in H-ras elements has been compared, employing nuclear extracts from human endometrial and ovarian lesions and from the adjacent normal tissue. Elevated binding of the glucocorticoid and estrogen receptors in the corresponding H-ras elements in almost all tissue pairs tested has been found. It is suggested that the H-ras proto-oncogene is hormonally regulated and directly implicated in human gynecological cancer through elevated, steroid-induced gene expression.
 ...
PMID:The association of the H-ras oncogene and steroid hormone receptors in gynecological cancer. 941 22

Anomalous diequatorial epoxide ring opening of 1 beta, 2 beta-oxido-cholesta-5,7-diene-3 beta, 25-diol 1 produces the 1 beta-hydroxy-2 alpha-chloro-provitamin 2 and its corresponding 1 beta-hydroxy-provitamin 3. The provitamins 2 and 3 are transformed by irradiation and thermal isomerization to 2 alpha-chloro-1-epicalcitriol NS3 (4) and 1-epicalcitriol NS8 (5), respectively. These two A-ring derivatives were tested for their in vitro biological activity in the mesenchymal, murine cell line C3H10T1/2, and their effects were compared with those of the native vitamin D3 derivatives 25(OH)D3 and 1.25(OH)2D3. NS3 and NS8 showed marked differences in their affinity for the vitamin D binding protein (DBP) and in their ability to inhibit cell proliferation. NS8 has the ability to bind to a high-affinity DBP-binding site for which 25(OH)D3 has none affinity. The 2 alpha-chloro-substitution (NS3) prevents binding to the postulated noncompetitive, NS8-specific DBP-binding site and diminishes the affinity to the vitamin D receptor (VDR) and therefore diminishing NS3's biological abilities. The elucidation of the structure-function relationships at the DBP-binding-sites could have major impact on the development of new vitamin D3 derivatives with extended serum half-life.
Steroids 1998 Jan
PMID:Synthesis and biological activities of 2 alpha-chloro-1-epicalcitriol and 1-epicalcitriol. 943 92

Dengue virus NS2/NS3 protease because of its ability to cleave viral proteins is considered as an attractive target to screen antiviral agents. Medicinal plants contain a variety of phytochemicals that can be used as drug against different diseases and infections. Therefore, this study was designed to uncover possible phytochemical of different classes (Aromatic, Carbohydrates, Lignin, Saponins, Steroids, Tannins, Terpenoids, Xanthones) that could be used as inhibitors against the NS2B/NS3 protease of DENV. With the help of molecular docking, Garcinia phytochemicals found to be bound deeply inside the active site of DENV NS2B/NS3 protease among all tested phytochemicals and had interactions with catalytic triad (His51, Asp75, Ser135). Thus, it can be concluded from the study that these Gracinia phytochemicals could serve as important inhibitors to inhibit the viral replication inside the host cell. Further in-vitro investigations require confirming their efficacy.
...
PMID:Computer Aided Screening of Phytochemicals from Garcinia against the Dengue NS2B/NS3 Protease. 2474 49