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

Biotin deficiency and biotin excess have both been found to affect reproduction and cause teratogenic effects. In the reproductive tract, however, the effects of biotin have not been well established yet. We investigated the effects of varying biotin content diets on the oestrus cycle, ovarian morphology, estradiol and progesterone serum levels, and the uterine mRNA abundance of their nuclear receptors, as well as on the activity of the estradiol-degrading group of enzymes cytochrome P450 (CYP) in the liver. Three-week-old female BALB/cAnN Hsd mice were fed a biotin-deficient, a biotin-control, or a biotin-supplemented diet (0, 7.2 or 400 micromol of free biotin/kg diet, respectively) over a period of nine weeks. Striking effects were observed in the biotin-deficient group: mice showed arrested estrous cycle on the day of diestrus and changes in ovary morphology. Estradiol serum concentration increased 49.2% in biotin-deficient mice compared to the control group, while the enzymatic activities of CYP1A2 and CYP2B2 increased (P<0.05). The mRNA abundance of nuclear estrogen and progesterone receptors decreased in the biotin-deficient mice. In the biotin-supplemented group we found that, in spite of a significant (P<0.05) decrease in the number of primary and Graafian follicles and in CYP1A2 activities, mice exhibited 105.4% higher serum estradiol concentration than the control group. No changes in the expression of the nuclear receptors were observed. No significant differences were observed in serum progesterone among the groups. Our results indicate that both the deficiency and the excess of biotin have significant effects on the female mouse reproductive system.
Steroids 2009 Oct
PMID:Biotin deficiency and biotin excess: effects on the female reproductive system. 1954 Feb 54

Epidemiological studies have revealed a protective role of oestrogens against the promotion of colorectal cancer (CRC). Therefore, the oestrogen metabolism status of colonic cells is studied to explain it. Loss of function of adenomatous polyposis coli (Apc) gene product is an early and frequent event in human colorectal carcinogenesis. Normal (Apc(+/+)) and premalignant (Apc(multiple intestinal neoplasia (Min)/+)) mouse colonic epithelial cells were used to compare their respective metabolic capabilities towards oestradiol-17beta (E(2)beta), with or without an inducer of the CYP1 family, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In both cell types, the major metabolite was oestradiol-17beta-3-glucuronide. The formation of catechol (CE) metabolites by cytochromes P450 of the CYP1 family and their derivatives was shown. Among these metabolites, several O-methyl-ether derivatives were detected, as unconjugated metabolites in Apc(+/+) cells and as glucuroconjugates in Apc(Min/+) cells, after TCDD treatment. Apc(Min/+) cells are metabolically more competent than Apc(+/+) cells to produce different hydroxylated metabolites as well as glucuroconjugates. Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) experiments corroborate these results. Indeed, induction by TCDD has prevailing effects in gene expression of CYP1A1, CYP1A2 and CYP1B1 in Apc(Min/+) cells, compared with Apc(+/+) ones. Apc(Min/+) cells displayed higher rates of oestrogen metabolic biotransformation than Apc(+/+) ones, but exhibited two opposite tendencies. Apc(Min/+) cells were able to detoxify E(2)beta mainly by the formation of glucuronides and displayed at the same time a striking potential to bioactivate E(2)beta by producing only the electrophilic 2-CE derivatives, not the 4-CE ones, even though a significant CYP1B1 mRNA induction was noticed. These specific electrophilic metabolites may form DNA adducts but are not prone to generate new mutations. Interestingly, the ultimate 2-O-methyl-ether metabolite of E(2)beta may be an endogenous protective factor against CRC promotion given its recognised anti-angiogenic and pro-apoptotic properties.
Steroids 2010 Oct
PMID:Metabolic bioactivation of oestradiol-17beta (E2beta) in mouse colon epithelial cells bearing ApcMin mutation. 2041 21

Rhizoma Paridis Saponins (RPS), which is the effective part of Rhizoma Paridis, showed strong activity against lung cancer and hepatocarcinoma. In this research, a combination of RPS with cyclophosphamide (CTX) was used to treat hepatocarcinoma in mice. Although no active enhancement of activity was observed, some attenuation of the toxicity of RPS in combination with CTX occurred. In order to explain this phenomenon, we carried out research on the effects of Rhizoma Paridis Saponins on the activities of cytochrome p450 enzymes CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2E1 and CYP3A4. The results indicated that RPS significantly influenced the activity of CYP2B6 and CYP3A4 through the inhibition of protein expression. However, RPS did not affect the activity of CYP1A2, CYP2A6, CYP2C9 and CYP2E1 in rats in vivo. These results suggested that RPS inhibited the conversion of cyclophosphamide into active metabolites and inactive byproducts through the reduced activities of CYP2B6 and CYP3A4. Therefore, it's essential to pay attention to CYP2B6- and CYP3A4-mediated herb-drug interactions between RPS and other drugs.
Steroids 2014 Feb
PMID:Combination therapy of cyclophosphamide and Rhizoma Paridis Saponins on anti-hepatocarcinoma mice and effects on cytochrome p450 enzyme expression. 2429 18