الملخص
Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most fatal form of CAH, as it disrupts adrenal and gonadal steroidogenesis. Most cases of lipoid CAH are caused by recessive mutations in the gene encoding steroidogenic acute regulatory protein (StAR). Affected patients typically present with signs of severe adrenal failure in early infancy and 46,XY genetic males are phenotypic females due to disrupted testicular androgen secretion. The StAR p.Q258X mutation accounts for about 70% of affected alleles in most patients of Japanese and Korean ancestry. However, it is more prevalent (92.3%) in the Korean population. Recently, some patients have been showed that they had late and mild clinical findings. These cases and studies constitute a new entity of 'nonclassic lipoid CAH'. The cholesterol side-chain cleavage enzyme, P450scc (CYP11A1), plays an essential role converting cholesterol to pregnenolone. Although progesterone production from the fetally derived placenta is necessary to maintain a pregnancy to term, some patients with P450scc mutations have recently been reported. P450scc mutations can also cause lipoid CAH and establish a recently recognized human endocrine disorder.
الموضوعات
Female , Humans , Male , Pregnancy , Alleles , Asian People , Cholesterol , Cholesterol Side-Chain Cleavage Enzyme , Gonads , Hyperplasia , Placenta , Pregnenolone , Progesteroneالملخص
Objective To investigate the association between polymorphism of cytochrome P450 subfamily Ⅺ A polypeptide 1 (CYP11A1) gene and polycystic ovarian syndrome (PCOS) in Chinese population. Methods From May 2005 to Dec.2008,290 PCOS cases treated in the First affiliated hospital of Anhui Medical University matched with 344 reproductive women as controls were enrolled in this study. Genotypes of 7 tagging single nucleotide polymorphisms(tSNP,rs12438594,rs4077582,rs9806234,rsl6968477,rs4887139,rs1843090,rsl 1632698)covering CYP11A1 gene (r~2≥0.8) and 3 microsatellite markers (D15S1547,D16S520,D15S1546) were chosed from the phase II database of Han population in HapMap data.Genotype and frequency of allele were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and haplotype of gene polymorphism were analyzed in 290 PCOS cases and 344 controls.Results Among 7 tSNPs and 3 microsatellite markers,the frequency of rs4077582,D15S1547,D15S1546 and rsl 1632698 between two groups reached statistical difference (P =0.010,0.044,0.018 and 0.026).The allele frequency of rs4O77582,rs4887139,rsl843090,D15S1547 and Dl 6S520 showed significant difference between two groups(P=0.002,0.048,0.030,0.001 and 0.024).Among 5 haplotype of CYP11A1(ACGCA13/6/9AG,ACGTA16/6/11AA,GCACG12/8/8AA,GTACA14/4/7GG,GTGCA13/6/7AG),the frequency of GTACA14/4/7GG and ACGCA13/6/9AG were 7.8% (45/580) and 25.3% (147/580) in PCOS group and 11.9% and 19.6% in control group,which showed statistical difference (P< 0.05 ).There was no significant difference in the level of serum androgen at difference genotype from rs4077582 between two groups (P>0.05).Conclusion The polymorphism of CYP11A1 gene was associated with PCOS,however,the relationship between gene sequence covered by tSNP/microsatellite markers and hyperandrogenism of PCOS should be further investigated.
الملخص
Objective To evaluate the changes in the expression of cytochrome cholesterol side chain cleavage enzyme (P450scc) in the brain of morphine-dependent rats. Methods Twenty-four male SD rats aged 4-8 months weighing 180-200 g were randomly divided into 3 groups (n = 8 each): group Ⅰ normal saline (group NS), group Ⅱ morphine dependence (group MD) and group Ⅲ morphine withdrawal (group MW). In group MD and MW, the rats were given intraperitoneally increasing doses of morphine starting from 5 mg/kg to 10, 15, 20, 30, 40 and 50 mg/kg twice a day for 7 days. In group NS, the rats were given equal volume of normal saline instead of morphine. The rats were decapitated 1 h after last injection in group NS and MD. In group MW, naloxone 2 mg/kg was given 1 h after last injection, and then the animals were decapitated 30 min after withdrawal symptoms were observed. The brains were immediately removed and the frontal cortex, hippocampus, striatum and thalamus were separated. The expression of P450see was determined by Western blot. Results The expression of P450scc in the frontal cortex, hippocampus and striatum was significantly decreased in group MD and MW compared with group NS (P<0.05). Conclusion The down-regulation of P450scc expression might be involved in the development of morphine dependence, but it is not involved in the morphine withdrawal.
الملخص
Objective To investigate the expression of mRNAs for cholesterol side chain cleavage enzyme (p450 scc), 17?-hydroxylase / C17-20 lyase (P450 C17) and 3?-hydroxysteroid dehydrogenase (3?-HSD) in frontal cortex, amygdala, hippocampus, striatum and midbrain of morphine dependence rats.Methods Twenty-one male SD rats were randomly divided into 3 groups with 7 animals in each group: (1) control group (group C) ; (2) morphine dependence group (group D) and (3) morphine withdrawal group (group W). In group D and W the animals were given intraperitoneally increasing doses of morphine starting from 5 mg?kg-1 to 10, 15, 20, 30, 40 and 50 mg?kg-1 twice a day for 7 days. In group C the animals were given normal saline instead of morphine. In group C and D the animals were decapitated 1 h after last injection. In group W naloxone 2 mg?kg-1 was given 1h after last morphine injection, then the animals were decapitated 30 min after withdrawal symptoms were observed. The brains were immediately removed and the frontal cortex, amygdala, hippocampus, striatum and midbrain were separated. The expression of mRNAs for the three steroidogenic enzymes in the different brain regions of rats were determined by RT-PCR.Results The expression of P450scc mRNA in striatum and 3?-HSD mRNA in amygdala, striatum and frontal cortex decreased in group D compared with group C. The expression of 3?-HSD mRNA increased in morphine withdrawal group compared with group D.Conclusion The gene expression of steroidogenic enzymes decreases in some brain regions of morphine dependence rats, suggesting that endogenous neurosteroids might be involved in morphine dependence.