Analysis of CYP17A1 gene variants in 5 patients with 17-hydroxylase deficiency / 中华医学遗传学杂志

Objective@#To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency (17-OHD).@*Methods@#Peripheral blood samples were collected with informed consent. Variants of CYP17A1 gene were screened by PCR and Sanger sequencing. Suspected mutations were validated in other members of the pedigrees.@*Results@#Gene sequencing has identified a homozygous c. 985_987delTACinsAA (Y329Kfs) mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3. Case 1 was found to harbor compound heterozygous mutations c. 1459_1467del9 (p.D487_F489del) and c. 1244-3C>A. The parents and brother of cases 2 and 5 were heterozygous carriers of a c. 985_987delTACinsAA(Y329Kfs) mutation.@*Conclusion@#Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD, for which c. 985_987delTACinsAA(Y329Kfs) is the most common. The c. 1244-3C>A is a novel mutation. Above results have facilitated genetic counseling for the affected families.

Functional Identification of Compound Heterozygous Mutations in the CYP17A1 Gene Resulting in Combined 17α-Hydroxylase/17,20-Lyase Deficiency

BACKGROUND: We previously reported a patient with congenital adrenal hyperplasia (CAH) with compound heterozygous mutations in the cytochrome P450 17A1 (CYP17A1) gene. One allele had a p.His373Leu and the other a new p.Glu383fsX36 mutation. The aim of this study was to investigate the functional properties of a new allele present in a compound heterozygote of CYP17A1. METHODS: To understand how p.His373Leu and p.Glu383fsX36 affect P450c17 enzymatic activity, wild type and mutant CYP17A1 cDNAs were cloned into flag-tagged pcDNA3 vector and introduced into human embryonic kidney cells 293T (HEK293T) cells. Protein expression levels of CYP17A1 were then analyzed. And the activities of 17α-hydroxylase and 17,20-lyase of CYP17A1 were evaluated by measuring the conversion of progesterone to 17α-hydroxyprogesterone and of 17α-hydroxypregnenolone to dehydroepiandrosterone, respectively. In addition a computer model was used to create the three-dimensional structure of the mutant CYP17A1 enzymes. RESULTS: Production of the p.His373Leu mutant protein was significantly lower than that of the wild type protein, and the p.Glu383fsX36 protein was hardly produced. Similarly the enzymatic activity derived from the p.His373Leu mutant vector was significantly lower than that obtained from the wild type vector, and little activity was obtained from the p.Glu383fsX36 vector. Three-dimensional modeling of the enzyme showed that p.His373 was located in region important for heme-binding and proper folding. Neither the p.His373Leu nor the p.Glu383fsX36 mutant protein formed a heme-binding structure. CONCLUSION: Enzyme activity measured in both mutants disappeared completely in both 17α-hydroxylase and 17,20-lyase. This result accounts for the clinical manifestations of the patient with the compound heterozygous CYP17A1 mutations.

17α-hydroxylase Deficiency Mimicking Hyperaldosteronism by Aldosterone-producing Adrenal Adenoma / 대한내과학회지

17α-hydroxylase deficiency is a rare cause of congenital adrenal hyperplasia and is characterized by primary amenorrhea, delayed puberty and hypertension. Although 17α-hydroxylase deficiency mimics mineralocorticoid-induced hypertension, impaired sexual development can aid in the differential diagnosis of this disease. A 32-year-old woman, who had a history of testicular feminization syndrome, presented with hypertension. Her aldosterone level was elevated whereas plasma renin activity was reduced, and her computed tomography scan showed a left adrenal adenoma, which was thought to be an aldosterone producing adenoma. A left adrenalectomy was performed to treat hypertension; however, the condition did not improve. The hormonal tests revealed high levels of plasma progesterone, mineralocorticoid and adrenocorticotropic hormone, and low levels of 17a hydroxyprogesterone, cortisol and sex hormones. The patient was diagnosed with 17α-hydroxylase deficiency and commenced on prednisolone, which controlled hypertension. Here, we report a case of 17α-hydroxylase deficiency mimicking hyperaldosteronism via aldosterone-producing adrenal adenoma.

A case of 17 alpha-hydroxylase deficiency / 대한생식의학회지

17alpha-hydroxylase and 17,20-lyase are enzymes encoded by the CYP17A1 gene and are required for the synthesis of sex steroids and cortisol. In 17alpha-hydroxylase deficiency, there are low blood levels of estrogens, androgens, and cortisol, and resultant compensatory increases in adrenocorticotrophic hormone that stimulate the production of 11-deoxycorticosterone and corticosterone. In turn, the excessive levels of mineralocorticoids lead to volume expansion and hypertension. Females with 17alpha-hydroxylase deficiency are characterized by primary amenorrhea and delayed puberty, with accompanying hypertension. Affected males usually have female external genitalia, a blind vagina, and intra-abdominal testes. The treatment of this disorder is centered on glucocorticoid and sex steroid replacement. In patients with 17alpha-hydroxylase deficiency who are being raised as females, estrogen should be supplemented, while genetically female patients with a uterus should also receive progesterone supplementation. Here, we report a case of a 21-year-old female with 17alpha-hydroxylase deficiency who had received inadequate treatment for a prolonged period of time. We also include a brief review of the recent literature on this disorder.

Mechanism of Bushen huoxue huatan recipe improving hyperandrogenism in androgen-induced sterile rats / 第二军医大学学报

Objective To observe the therapeutic effect of Bushen huoxue huatan recipe (BHHR) on androgen-induced sterilized rats (ASR) and the expression of androgen synthase and metabolic enzymes in the ovary of ASR before and after treatment with BHHR, and to discuss the possible mechanism. Methods Female SD rats of 9-day old were injected subcutaneously with testosterone propionate (1. 25 mg) to create model. The model ratswere randomly divided into 3 groups: model group (treated with distilled water by gastrogavage, 10 mL/kg)' metformin therapy group (gastrogavage, 0. 1 g/kg) and BHHR therapy group (gastrogavage, 10 mL/kg)' with 13 animals in each group. Ten rats with normal estrous cycle served as normal controls. The body mass' sexual cycle recovery and ovary mass/body mass ratio were observed after 28-day treatment. Serum testosterone level was measured by radioimmunoassay; the expressions of 3(-hydroxylsteroid dehyrogenase (3β-HSD) cytochrome P450 17α-crhydroxylase/17, 20-lyase (CYP17) and P450 aromatase (P450arom) in ovary were detected by quantitative immunohistochemistry method. Results (1) Significantly more rats in the metformin and BHHR groups had sexual cycle recovery compared with that in themodtl group (P 0. 05). Conclusion BHHR can reduce serum testosterone levels in ASR rat, which might be through up-regulating the expression of the androgen metabolism enzyme P450arom.

Male Pseudohermaphroditism Presented with Sudden Cardiac Arrest

Torsades de Pointes is a life-threatening arrhythmia associated with a number of causes, but is very rare among endocrinologic disorders. We report a case of male pseudohermaphroditism with hyperaldosteronism due to a 17alpha-hydroxylase deficiency presented with sudden cardiac arrest.

Clinical study on 48 cases with complete 17α-hydroxylase deficiency / 中华妇产科杂志

Objective To investigate efficient diagnosis and treatment of 17α-hydroxylase (17OHD) deficiency by summarizing clinical characteristics of those patients.Methods From January 1983 to January 2010,48 cases with 17OHD in Peking Union Medical College Hospital were studied retrospectively.Results Among 48 patients with 17OHD,karyotype analysis showed,12 cases with 46,XX and 36 cases with 46,XY.The 46,XX karyotype and 46,XY karyotype with complete 17OHD had typical clinical presentation of amenorrhea [ 12/12,100％ ( 36/36 ) ],no typical spontaneous puberty [ 12/12,13.9％ (5/36) ],Hypertension [ 11/12,100％ ( 36/36 ) ],hypokalemia [ K +:( 2.6 ± 0.7 ),( 2.8 ± 0.7 )mmol/L],hypergonadotropin [ follicle-stimulatinghormone ( FSH ):( 51 ± 35 ),( 79 ± 46 ) U/L,luteinizing hormone( LH ):( 27 ± 14 ),(49 ± 37 ) U/L ],impaired production of sex hormones [ testosterone(T):0.003,0.005 nmol/L; estradiol ( E2 ):26.86,10.64 pmol/L ],hyper-progesterone [ (P):( 32 ± 15 ),( 29 ± 23) nmol/L],impaired production of 17α-hydroxyprogesterone ( 17α-OHP ) [ ( 2.5 ± 1.1 ),( 2.4 ±1.7) nmol/L],ACTH hypersecreation (91.8,114.0 pmol/L).ACTH stimulating test did not elevated in 17α-OHP and cortisol.Conclusion When patients with elevated basal serum levels of progesterone higher than that of ovulation period in addition to clinical symptoms,examination about 17OHD should be warranted.

Limited Expression of Cytochrome P450 17alpha-Hydroxylase/17,20-Lyase in Prostate Cancer Cell Lines

PURPOSE: Cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17A1) is a key enzyme in the androgen biosynthesis pathway. CYP17A1 has been focused on because of the promising results of a potent CYP17A1 inhibitor in the treatment of castration-resistant prostate cancer (CRPC). A hypothesis that intratumoral androgenesis may play a role in the progression of CRPC has recently been postulated. Thus, we evaluated whether commonly used prostate cancer cell lines express CYP17A1. MATERIALS AND METHODS: Androgen-sensitive LNCaP and androgen-insensitive PC-3 and DU145 cells were used. To evaluate the expression of CYP17A1 protein and RNA, we performed Western blotting and RT-PCR, respectively. RESULTS: We were unable to detect either CYP17A1 protein or RNA in any of the cell lines tested. We failed to detect any expression of CYP17A1, despite several repetitions of these techniques under different conditions. CONCLUSIONS: The expression of CYP17A1 protein and RNA in LNCaP, PC-3, and DU145 cells appears to be either absent or too low for detection. The mechanism of action of abiraterone acetate, a CYP17A1 inhibitor, may be related more to adrenal androgen blockade than to intratumoral androgenesis.

Establishment of an assay for detection of gene mutation in congenital adrenal hyperplasia / 中华检验医学杂志

Objective To establish a method of gene mutation detection for congenital adrenal hyperplasia (CAH) by using sequencing, single nucleotide polymorphisms (SNP) analysis and T-A cloning. Methods The blood samples of 33 patients with 21-hydroxylase deficiency (21-OHD) , 2 patients with 17α-hydroxylase deficiency (17-OHD) , the parents of all the patients and 105 healthy children were collected. Genomic DNA were extracted form the blood samples. To detect the gene mutation of CYP21A2,highly specific primers for CYP21A2 gene were designed according to the sequence differences between CYP21A2 gene and its pseudogene. The whole CYP21A2 gene was amplified and sequenced. SNP analysis and TA cloning of PCR products were also carried out. The molecular diagnosis of 17-OHD was based on the amplification and sequencing of CYP17A1 gene. Results The corresponding gene mutations was determined in all the patients based on the method established in this study. Thirteen mutations of CYP21A2 gene were identified in 33 patients with 21-OHD. The 3 most frequent mutation of CYP21A2 gene were IVS2-13A/C >G, p. I172N and chimeric mutation, which accounted for 32% (21/66) ,27% (18/66) and 15% (10/66) respectively. Ninety-one persent mutations of CYP21A2 gene resulted from pseudogene conversion. In 2 patients with 17-OHD, homozygous mutations of CYP17A1 gene, IVS4-6A > G and p. 487_489del were identified separately. All the gene mutations detected in the patients were inherited from their parents. No mutation of CYP21A2 gene or CYP17A1 gene was found in the healthy children. Conclusion A method of gene mutation detection for CAH has been established. It will be beneficial to clinical diagnosis of CAH.

Polymorphism in CYP17, GSTM1 and the progesterone receptor genes and its relationship with mammographic density

Radiologic breast density is one of the predictive factors for breast cancer and the extent of the density is directly related to postmenopause. However, some patients have dense breasts even during postmenopause. This condition may be explained by the genes that codify for the proteins involved in the biosynthesis, as well as the activity and metabolism of steroid hormones. They are polymorphic, which could explain the variations of individual hormones and, consequently, breast density. The constant need to find markers that may assist in the primary prevention of breast cancer as well as in selecting high risk patients motived this study. We determined the influence of genetic polymorphism of CYP17 (cytochrome P450c17, the gene involved in steroid hormone biosynthesis), GSTM1 (glutathione S-transferase M1, an enzyme involved in estrogen metabolism) and PROGINS (progesterone receptor), for association with high breast density. One hundred and twenty-three postmenopausal patients who were not on hormone therapy and had no clinical or mammographic breast alterations were included in the present study. The results of this study reveal that there was no association between dense breasts and CYP17 or GSTM1. There was a trend, which was not statistically significant (P = 0.084), towards the association between PROGINS polymorphism and dense breasts. However, multivariate logistic regression showed that wild-type PROGINS and mutated CYP17, taken together, resulted in a 4.87 times higher chance of having dense breasts (P = 0.030). In conclusion, in the present study, we were able to identify an association among polymorphisms, involved in estradiol biosyntheses as well as progesterone response, and radiological mammary density.

Amenorréia primária e cariótipo XY: identificando pacientes em risco / Primary amenorrhea and XY karyotype: identifying patients in risk

OBJETIVO: verificar a prevalência e as características clínicas de pacientes com amenorréia primária e cariótipo XY avaliadas em nosso Serviço com o intuito de identificar achados que possam auxiliar em seu reconhecimento. MÉTODOS: no período de Janeiro de 1975 a Novembro de 2007, foram avaliadas 104 pacientes com amenorréia primária. Para todos os casos foi realizada a análise pelo cariótipo por bandas GTG. Destas, 21 (20,2%) apresentavam uma constituição 46,XY. Contudo, duas foram excluídas do estudo por terem prontuários incompletos. Das 19 pacientes que compuseram a amostra, a maior parte veio encaminhada pela ginecologia (63,2%). Suas idades variaram entre 16 e 41 anos (média de 22,1 anos). Realizou-se uma coleta de dados sobre sua história familiar e pregressa, exame físico e resultados de exames complementares. Para determinação dos seus diagnósticos levaram-se em consideração essas informações. RESULTADOS: a síndrome de resistência aos androgênios foi o diagnóstico predominante (n=12; 63,2%). Cinco pacientes (26,3%) apresentavam disgenesia gonadal pura XY (DGP XY), uma (5,3%) deficiência de 17-alfa hidroxilase e uma (5,3%) deficiência de 5-alfa redutase. Achados clínicos freqüentemente observados nessas pacientes incluíram desenvolvimento anormal dos caracteres sexuais secundários (n=19), agenesia uterina com vagina em fundo de saco (n=14), história familiar de amenorréia (n=8) e gônadas palpáveis no canal inguinal (n=5). Duas delas apresentavam história de hérnia inguinal. Hipertensão arterial sistêmica foi diagnosticada somente na paciente com deficiência de 17-alfa hidroxilase, e malignização gonadal, naquela com DGP XY. CONCLUSÕES: a freqüência de pacientes com cariótipo XY (20%) foi superior à usualmente descrita na literatura (3 a 11%). Acreditamos que isso tenha relação com a forma de encaminhamento das pacientes ao Serviço...

PURPOSE: to verify the prevalence and clinical characteristics of patients with primary amenorrhea and XY caryotype, evaluated in our Service, aiming at identifying findings which could help their recognition. METHODS: from January 1975 to November 2007, 104 patients with amenorrhea were evaluated. All the cases were analyzed by the caryotype by GTG bands. Among them, 21 (20.2%) presented a XY 46 constitution. Nevertheless, two of them were excluded from the study, because of incomplete data in their patient's chart. Most of the 19 patients who formed the sample had been referred to us by the gynecology clinics (63.2%). Their ages varied from 16 to 41 years old (an average of 22.1). Data were collected about their family and previous history, physical examination and results of complementary exams and the information was taken into consideration to determine the diagnosis. RESULTS: the predominant diagnosis was resistance to androgens syndrome (n=12; 63.2%); five patients (25.3%) presented XY pure gonadal dysgenesis (XY PGD), one (5.3%) 17 alpha-hydroxylase deficiency, and one (5.3%), 5 alpha-reductase deficiency. Clinical findings frequently found in these patients included abnormal development of secondary sexual characters (n=19), uterine agenesia with a blind vagina (n=14), family history of amenorrhea (n=8), and palpable gonads in the inguinal canal (n=5). Two of them presented a history of inguinal hernia. Systemic arterial hypertension was only diagnosed in the patient with 17 alpha-hydroxylase deficiency, and gonadal malignization, in the one with XY PGD. CONCLUSIONS: the rate of patients with XY caryotype (20%) was higher than the one described in the literature (3 to 11%). It is believed that this fact is related to the way patients are usually referred to our service. Some findings from the clinical history and from the physical examination should be evaluated as a routine in individuals with primary amenorrhea...

A case of primary amenorrhea with hypertension due to 17alpha-hydroxylase deficiency / 대한산부인과학회지

17alpha- hydroxylase deficiency is a rare form of congenital adrenal hyperplasia and characterized by the coexistance of hypertension caused by the hyperproduction of mineralocorticoid precursors and sexual abnormalities, such as female pseudohermaphroditism and sexually infantile female with 46,XX karyotype or male pseudohermaphroditism with 46, XY karyotype, due to impaired production of sex hormone. We experienced a case of 17alpha- hydroxylase deficiency (46,XX) presented with primary amenorrhea, sexual infantilism, and hypertension. We report this case with a brief review of the concerned literatures.

A Case of Male Pseudohermaphroditism due to 17alpha-Hydroxylase Deficiency / 대한불임학회지

Female phenotype of a 46,XY male may originates from male pseudohermaphroditism due to 17alpha-hydroxylase deficiency. Lack of cortisol increases adrenocorticotropic hormone (ACTH) and mineralocorticoid production, leading to low renin hypertention and hypokalemia. A 41-year-old phenotypic female presented primary amenorrhea and hypertension. In the hormonal profile, the levels of serum estradiol, testosterone, rennin, and cortisol were decreased and ACTH and deoxycorticosterone were increased. Laparoscopic bilateral gonadectomy was performed, and corticosteroid, antihypertensive drugs, and estrogen were administered. We report this case with a brief review of the literatures.

A case of primary amenorrhea due to 17alpha- hydroxylase deficiency / 대한내과학회지

The enzyme, 17 -hydroxylase, is necessary for both cortisol and estrogen synthesis. Deficiency of the hormone results in increased adrenocorticotrophic hormone (ACTH), follicle-stimulating hormone (FSH). Synthesis of progesterone, 11-deoxycorticosterone (DOC), corticosterone and aldosterone don't require the enzyme. The lack of estrogen results in primary amenorrhea and absent sexual maturation. The replacement of dexamethasone and estrogens has lowered the blood pressure and produced feminization. A 19-year-old female had 46,XX genotype and presented amonorrhea, absence of sexual characteristics, hypertension and hypokalemia. Endocrinologic studies demonstrated increased plasma progesterone, ACTH levels and low production of 17 -hydroxyprogesterone and testosterone. We report a rare case of 17 -hydroxylase deficency with a brief history and review of the literature.

Combined deficiency of steroid 17-?-hydroxylase/17 and 20-lyase induced by mutation of homozygous 985del TAC insAA of CYP17 gene / 解放军医学杂志

Objective To analyze the CYP17 gene of two sisters with combined 17-alpha-hydroxylase/17, 20-lyase deficiency, and that of their parents. Methods Genomic DNA of the four members was prepared from peripheral blood by standard methods. All the eight exons and intron/exon boundaries of CYP17 were PCR amplified and sequenced. All the hormone levels were measured by time-resolved immunofluorometric assay. Results Combined 17-?-hydroxylase/17, 20-lyase deficiency was confirmed by marked hormone change. Sequence analysis revealed that the sisters were homozygous 985delTACinsAA of CYP17, and their parents were heterozygous 985delTACinsAA. Conclusion Novel mutation of 985delTACinsAA in CYP17 was found in two sisters with 17-?-hydroxylase/17, 20-lyase deficiency. The homozygous one can induced the phenotype and the heterozygous one is a genomic marker.

A Case of Primary Amenorrhea due to 17 -Hydroxylase Deficiency / 대한내분비학회지

17 -Hydroxylase deficiency is a rare form of congenital adrenal hyperplasia that is characterized by primary amenorrhea, absence of secondary sex characteristics, hypertension, and a hypokalemic alkalosis that has resulted resulting from increased production of deoxycorticosterone and corticosterone by the adrenal. The diagnosis of this enzyme deficiency can be recognized by the increasing serum concentrations of steroid precursors, DOC and corticosterone and the decreasing concentrations of cortisol, and adrenal androgens. We diagnosed this in a 19 year old female who presented with primary amenorrhea. We report this case with a review of the literatures.

Incomplete P450 17 alpha enzyme deficiency:report of six cases / 中华妇产科杂志

Objectives To summarize the characteristics,differential diagnosis and management of incomplete 17 alpha-hydroxylase/17,20-1yase deficiency(17 OHD)of Chinese patients.Methods Six cases of incomplete 17 OHD from Peking Union Medical College Hospital were studied retrospectively through analyzing their clinical data,and the molecular pathogenic mechanism was discussed after literature review.Results Four cases of 46,XX incomplete 17 OHD were reported.The clinical characteristics included female phenotype,various degrees of breast development and absent or sparse axillary/pubic hair, oligomenorrhea or secondary amenorrhea,recurrent luteinized ovarian cysts,hypogonadism with persistent hyperprogesteronemia or high serum 17 alpha-hydroxyprogesterone level,with or without hypokalemic hypertension.There were also 2 cases of 46,XY incomplete 17 OHD,in which ambiguous genitalia were present besides hypokalemic hypertension.Conclusions Incomplete 17 OHD is a very rare form of congenital enzymatic deficiencies of steroid synthesis,which should be included in the differential diagnosis when there are menstrual disorders,sexual infantilism,recurrent ovarian cysts or ambiguous genitalia.Under such circumstances,hyperprogesteronemia offers a valuable clue for further investigation.

A case of male Pseudohermaphroditism due to 17alpha-Hydroxylase Deficiency / 대한산부인과학회잡지

A 21-year-old phenotypic female with 46,XY genotype presented with primary amenorrhea, headache, absence of secondary sex characteristics, and hypertension.Further evaluation confirmed male pseudohermaphroditism having no nterus and adnexase.After basic hormonal study and ACTH stimulation test, we concluded 17alpha-hydroxylase deficiency. Owing to the high risk of gonadal neoplasia in XY gonadal streaks, prophylactic removal of the steaks is recommended. Traditionally this procedure has been performed by laparotomy, but in this case laparoscopic gonadctomy was performed. Following treatment with hydrocrtisone, potassium, progesterone, 11-deoxycorticosterone, corticosterone and urinay pregnanediol levels were normalized. normal blood pressure measurements were achieved during treatment with hydrocortisone and estrogen with the patient. We report this case with a breif review of the literatures.

A Case of 17alpha-Hydroxylase Deficiency

A 12-year-old girl with hypertension, hypokalemia, cystic ovaries and absence of secondary sexual development is presented. Hormonal study revealed very low levels of cortisol, testosterone, estrogen, and high levels of progesterone, deoxycorticosterone, corticosterone, FSH and ACTH. Following treatment with dexamethasone and estrogen, the levels of the latter group remarkably decreased. Serum potassium level and blood pressure also became normal. With all the above hormonal profile and clinical findings, we reached the diagnosis of 17alpha-hydroxylase deficiency and report this case with the review of literature.

Changes in the gene expression of steroidogenic enzymes in the brain of morphine dependence rats / 中华麻醉学杂志

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.