Genomes and Genes
Gene Symbol: Srd5a1
Description: steroid 5 alpha-reductase 1
Alias: S5AR 1, 3-oxo-5-alpha-steroid 4-dehydrogenase 1, SR type 1, steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 1)
- Eicheler W, Seitz J, Steinhoff M, Forssmann W, Adermann K, Aumuller G. Distribution of rat hepatic steroid 5 alpha-reductase 1 as shown by immunohistochemistry. Exp Clin Endocrinol Diabetes. 1995;103:105-12 pubmed..After androgen-deprivation a considerable increase in immunoreactivity was seen in male rat liver cells, indicating androgen-dependent suppression of the enzyme in male liver. ..
- Uemura M, Tamura K, Chung S, Honma S, Okuyama A, Nakamura Y, et al. Novel 5 alpha-steroid reductase (SRD5A3, type-3) is overexpressed in hormone-refractory prostate cancer. Cancer Sci. 2008;99:81-6 pubmed
- El Awady M, El Garf W, El Houssieny L. Steroid 5alpha reductase mRNA type 1 is differentially regulated by androgens and glucocorticoids in the rat liver. Endocr J. 2004;51:37-46 pubmed..Moreover, our findings appear to indicate that regulation of 5alphaR1 gene is primarily at the post-transcriptional level. ..
- Andersson S, Bishop R, Russell D. Expression cloning and regulation of steroid 5 alpha-reductase, an enzyme essential for male sexual differentiation. J Biol Chem. 1989;264:16249-55 pubmed..The data suggest that the steroid 5 alpha-reductase gene is differentially regulated by testosterone in androgen-responsive versus non-responsive tissues. ..
- Bortolato M, Frau R, Orru M, Bourov Y, Marrosu F, Mereu G, et al. Antipsychotic-like properties of 5-alpha-reductase inhibitors. Neuropsychopharmacology. 2008;33:3146-56 pubmed publisher..induced no catalepsy in either the bar test or the paw test. Our results suggest that 5AR inhibitors elicit antipsychotic-like effects in animals and may be proposed as a putative novel target in the management of psychotic disorders. ..
- Fischer A, Gaedicke S, Frank J, Döring F, Rimbach G. Dietary vitamin E deficiency does not affect global and specific DNA methylation patterns in rat liver. Br J Nutr. 2010;104:935-40 pubmed publisher..Two enzymes, 5-?-steroid reductase type 1 (SRD5A1) and the regulatory subunit of ?-glutamylcysteinyl synthetase (GCLM), which are differentially expressed on the ..
- Shao T, Li H, Ittmann M, Cunningham G. Effects of dutasteride on prostate growth in the large probasin-large T antigen mouse model of prostate cancer. J Urol. 2007;178:1521-7 pubmed..These studies provide support for the hypothesis that a 5alpha-reductase inhibitor inhibits the initiation and/or progression of clinical prostate cancers. ..
- Castro B, Sanchez P, Torres J, Preda O, del Moral R, Ortega E. Bisphenol A exposure during adulthood alters expression of aromatase and 5?-reductase isozymes in rat prostate. PLoS ONE. 2013;8:e55905 pubmed publisher..Our results may offer new insights into the role of BPA in the development of prostate disease and may be of great value for studying the prostate disease risk associated with exposure to BPA in adulthood. ..
- Morita K, Arimochi H, Her S. Serotonergic 5-HT2A receptor stimulation induces steroid 5alpha-reductase gene expression in rat C6 glioma cells via transcription factor Egr-1. Brain Res Mol Brain Res. 2005;139:193-200 pubmed
- Sanchez P, Torres J, Castro B, Olmo A, del Moral R, Ortega E. Expression of steroid 5?-reductase isozymes in prostate of adult rats after environmental stress. FEBS J. 2013;280:93-101 pubmed publisher..Further research is warranted to explore these effects of environmental stress on human health and their implications for environmental and occupational health policies. ..
- Yokoi H, Tsuruo Y, Miyamoto T, Ishimura K. Steroid 5 alpha-reductase type 1 immunolocalized in the adrenal gland of normal, gonadectomized, and sex hormone-supplemented rats. Histochem Cell Biol. 1998;109:127-34 pubmed
- Lauber M, Lichtensteiger W. Ontogeny of 5 alpha-reductase (type 1) messenger ribonucleic acid expression in rat brain: early presence in germinal zones. Endocrinology. 1996;137:2718-30 pubmed..g. proliferation and differentiation. As several types of steroid hormones can serve as substrates for 5alpha-reductase, it remains to be elucidated which metabolite(s) mediates the possible actions of the_ enzyme in CNS development. ..
- Her S, Lee M, Morita K. Trichostatin A stimulates steroid 5alpha-reductase gene expression in rat C6 glioma cells via a mechanism involving Sp1 and Sp3 transcription factors. J Mol Neurosci. 2010;41:252-62 pubmed publisher..Thus, both Sp1 and Sp3 are considered to play a physiological role in the regulation of 5alpha-R gene expression, and hence the production of 5alpha-reduced neurosteroids in glial cells. ..
- Her S, Arimochi H, Morita K. Nerve growth factor induces elevation of steroid 5alpha-reductase mRNA levels in rat C6 glioma cells through expression of transcription factor Egr-1. Brain Res Mol Brain Res. 2004;126:157-64 pubmed
- Morita K, Arimochi H, Tsuruo Y. Adrenergic activation of steroid 5alpha-reductase gene expression in rat C6 glioma cells: involvement of cyclic amp/protein kinase A-mediated signaling pathway. J Mol Neurosci. 2004;22:205-12 pubmed
- van der Eerden B, Lowik C, Wit J, Karperien M. Expression of estrogen receptors and enzymes involved in sex steroid metabolism in the rat tibia during sexual maturation. J Endocrinol. 2004;180:457-67 pubmed..This process may contribute to the beneficial effects of estrogen on bone mass accrual, possibly by intracrinology. ..
- Thigpen A, Russell D. Four-amino acid segment in steroid 5 alpha-reductase 1 confers sensitivity to finasteride, a competitive inhibitor. J Biol Chem. 1992;267:8577-83 pubmed..Finasteride was a competitive inhibitor of the native and all chimeric enzymes tested, suggesting that the tetrapeptide segments form a portion of the substrate-binding domain of steroid 5 alpha-reductase. ..
- Killian J, Pratis K, Clifton R, Stanton P, Robertson D, O Donnell L. 5alpha-reductase isoenzymes 1 and 2 in the rat testis during postnatal development. Biol Reprod. 2003;68:1711-8 pubmed..We conclude that both 5alphaR1 and 5alphaR2 isoenzymes are involved in the peak of 5alpha-reduced androgen biosynthesis in the testis during the pubertal initiation of spermatogenesis. ..
- Berman D, Tian H, Russell D. Expression and regulation of steroid 5 alpha-reductase in the urogenital tract of the fetal rat. Mol Endocrinol. 1995;9:1561-70 pubmed..However, no evidence for feedforward regulation of either 5 alpha-reductase gene was detected in the fetus. ..
- Pampori N, Shapiro B. Gender differences in the responsiveness of the sex-dependent isoforms of hepatic P450 to the feminine plasma growth hormone profile. Endocrinology. 1999;140:1245-54 pubmed
- Livingstone D, Barat P, Di Rollo E, Rees G, Weldin B, Rog Zielinska E, et al. 5?-Reductase type 1 deficiency or inhibition predisposes to insulin resistance, hepatic steatosis, and liver fibrosis in rodents. Diabetes. 2015;64:447-58 pubmed publisher..Variations in 5?R1 activity in obesity and with nonselective 5?-reductase inhibition in men with prostate disease may have important consequences for the onset and progression of metabolic liver disease. ..
- Tian H, Russell D. Expression and regulation of steroid 5 alpha-reductase in the genital tubercle of the fetal rat. Dev Dyn. 1997;209:117-26 pubmed..Together with genetic data, the results implicate the mesenchyme as the crucial cell type in formation of the male external genitalia. ..
- Taylor M, Bhattacharyya A, Collins D. Inhibition of rat steroid 5 alpha-reductase (isozyme 1) by suramin. Steroids. 1995;60:452-6 pubmed..These results suggest that suramin inhibits rat steroid 5 alpha-reductase (isozyme 1) at the level of NADPH binding to the enzyme. ..
- Wako K, Kawasaki T, Yamana K, Suzuki K, Jiang S, Umezu H, et al. Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer. J Clin Pathol. 2008;61:448-54 pubmed..The expression scores for AR, 5alpha-reductase type 1 (SRD5A1), 5alpha-reductase type 2 (SRD5A2), and aldo-keto reductase family 1 member C3 (AKR1C3) in the metastatic lesion ..
- Pratis K, O DONNELL L, Ooi G, Stanton P, McLachlan R, Robertson D. Differential regulation of rat testicular 5alpha-reductase type 1 and 2 isoforms by testosterone and FSH. J Endocrinol. 2003;176:393-403 pubmed
- Poletti A, Celotti F, Rumio C, Rabuffetti M, Martini L. Identification of type 1 5alpha-reductase in myelin membranes of male and female rat brain. Mol Cell Endocrinol. 1997;129:181-90 pubmed..The experiments were performed on the optic nerve, a myelinated structure very rich in 5alpha-R activity and the results clearly indicated the presence of a specific type 1 enzyme immunoreactivity in the myelin sheaths of axons. ..
- Maayan R, Fisch B, Galdor M, Kaplan B, Shinnar N, Kinor N, et al. Influence of 17beta-estradiol on the synthesis of reduced neurosteroids in the brain (in vivo) and in glioma cells (in vitro): possible relevance to mental disorders in women. Brain Res. 2004;1020:167-72 pubmed..This process may be relevant to psychopathological disorders that are ascribed to drastic alterations in estrogen levels, such as premenstrual syndrome, pregnancy-related mental disorders, and postpartum "blues". ..
- Anbalagan J, Sashi A, Vengatesh G, Stanley J, Neelamohan R, Aruldhas M. Mechanism underlying transient gestational-onset hypothyroidism-induced impairment of posttesticular sperm maturation in adult rats. Fertil Steril. 2010;93:2491-7 pubmed publisher..Transient gestational-onset hypothyroidism affects male fertility by impairing posttesticular sperm maturation process in the epididymis, owing to subnormal androgen(s) bioavailability, AR expression, and AR functional activity. ..
- Stuart J, Lee F, Simpson Noel D, Kadwell S, Overton L, Hoffman C, et al. Pharmacokinetic parameters and mechanisms of inhibition of rat type 1 and 2 steroid 5alpha-reductases: determinants for different in vivo activities of GI198745 and finasteride in the rat. Biochem Pharmacol. 2001;62:933-42 pubmed..Therefore, we hypothesize that because of its pharmacokinetic parameters and increased potency against r5AR1, GI198745 is more effective than finasteride in preventing the growth of the rat prostate. ..
- Torres J, Ortega E. Steroid 5alpha-reductase isozymes in the adult female rat brain: central role of dihydrotestosterone. J Mol Endocrinol. 2006;36:239-45 pubmed..These results open up a new research line that may lead to a better understanding of the physiology of the CNS. ..
- Romero M, Vila R, Fernández López J, Esteve M, Alemany M. Oleoyl-estrone increases adrenal corticosteroid synthesis gene expression in overweight male rats. Steroids. 2010;75:20-6 pubmed publisher..e. serum turnover), a process not driven by limited energy availability but directly related to the administration of OE. ..
- Lopez Solache I, Luu The V, Seralini G, Labrie F. Heterogeneity of rat type I 5 alpha-reductase cDNA: cloning, expression and regulation by pituitary implants and dihydrotestosterone. Biochim Biophys Acta. 1996;1305:139-44 pubmed..The results demonstrated that rat type I 5 alpha-reductase mRNA is stimulated by pituitary hormones and castration but is decreased by DHT and hypophysectomy. ..
- Noguchi S, Ohno Y, Aoki N. Adrenocortical insufficiency in Otsuka Long-Evans Tokushima Fatty rats, a type 2 diabetes mellitus model. Metabolism. 2007;56:1326-33 pubmed..We showed that adrenocortical insufficiency and adrenal atrophy were acquired in OLETF rats, and the possibility of elevated serum leptin relates to this phenomenon...
- Sanchez P, Torres J, Vílchez P, del Moral R, Ortega E. Effects of sulpiride on prolactin and mRNA levels of steroid 5alpha-reductase isozymes in adult rat brain. Neurochem Res. 2008;33:820-5 pubmed..Since 3alpha,5alpha-reduced neurosteroids and PRL exert anxiolytic effects in response to stress, these molecules and 5alpha-R may possibly participate in a common pathway of significant adaptation to stress situations. ..
- Szécsi M, Ondré D, Toth I, Magony S, Wolfling J, Schneider G, et al. Determination of rat 5alpha-reductase type 1 isozyme activity and its inhibition by novel steroidal oxazolines. Acta Biol Hung. 2010;61:274-81 pubmed publisher..Tests revealed moderate inhibitory actions compared to finasteride, nevertheless, results provide interesting structure-activity relationship data. ..
- Kayampilly P, Wanamaker B, Stewart J, Wagner C, Menon K. Stimulatory effect of insulin on 5alpha-reductase type 1 (SRD5A1) expression through an Akt-dependent pathway in ovarian granulosa cells. Endocrinology. 2010;151:5030-7 pubmed publisher..The elevated levels of these metabolites, in turn, might adversely affect growth and proliferation of granulosa cells, thereby impairing follicle growth and ovulation. ..
- Rossetti M, Varayoud J, Moreno Piovano G, Luque E, Ramos J. Environmental enrichment attenuates the age-related decline in the mRNA expression of steroidogenic enzymes and reduces the methylation state of the steroid 5Î±-reductase type 1 gene in the rat hippocampus. Mol Cell Endocrinol. 2015;412:330-8 pubmed publisher..Thus, sensory and social stimulation attenuate the age-related decline in the mRNA expression of hippocampal steroidogenic enzymes. Epigenetic mechanisms associated with differential promoter methylation could be involved. ..
- Sanchez P, Torres J, Vílchez P, del Moral R, Ortega E. Effects of sulpiride on mRNA levels of steroid 5alpha-reductase isozymes in prostate of adult rats. IUBMB Life. 2008;60:68-72 pubmed publisher..Although a direct effect of sulpiride on prostate gland cannot be ruled out, hyperprolactinemia may be a factor to be considered in aging males, in whom prostatic diseases such as BPH and PCa are more frequent. ..
- Sanchez P, Torres J, Gavete P, Ortega E. Effects of swim stress on mRNA and protein levels of steroid 5alpha-reductase isozymes in prefrontal cortex of adult male rats. Neurochem Int. 2008;52:426-31 pubmed..These data may open up a new research line that could improve our understanding of the role of 5alpha-R isozymes in processes that accompany stress situations. ..
- Lewis M, Wiebe J, Heathcote J. Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma. BMC Cancer. 2004;4:27 pubmed..Semi-quantitative RT-PCR was used to compare relative expression (as a ratio of 18S rRNA) of 5alphaR type 1 (SRD5A1), 5alphaR type 2 (SRD5A2), 3alpha-HSO type 2 (AKR1C3), 3alpha-HSO type 3 (AKR1C2) and 20alpha-HSO (AKR1C1) mRNAs ..
- Morita K, Kuwada A, Fujihara H, Morita Y, Sei H. Changes in the expression of steroid metabolism-related genes in rat adrenal glands during selective REM sleep deprivation. Life Sci. 2003;72:1973-82 pubmed..These results indicate that REM sleep deprivation by itself may affect the expression of steroid metabolism-related genes in the adrenal gland, suggesting a possible relation between REM sleep and adrenocortical steroid metabolism. ..
- Taylor M, Wang M, Bhattacharyya A, Chiang N, Tai H, Collins D. Expression of rat steroid 5 alpha-reductase (isozyme-1) in Spodoptera frugiperda, SF21, insect cells: expression of rat steroid 5 alpha-reductase. Steroids. 1997;62:373-8 pubmed..Photoaffinity labeling by [2'-32P]-2-azido-NAD P+ ([2'-32P]2N3-NAD P+) and [1,2(3)H] N-(benzylbenzoyl)-3-oxo-4-aza-4-methyl-5 alpha androstane-17 beta-carboxamide ([3H]-4MABP) also showed a labeled protein band at 26 kDa. ..
- Xu Y, Dalrymple S, Becker R, Denmeade S, Isaacs J. Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers. Clin Cancer Res. 2006;12:4072-9 pubmed..e., SRD5A1 and SRD5A2)...
- Aizawa K, Iemitsu M, Maeda S, Otsuki T, Sato K, Ushida T, et al. Acute exercise activates local bioactive androgen metabolism in skeletal muscle. Steroids. 2010;75:219-23 pubmed publisher..Finally, the expression of AR was significantly higher in female rats, but not in males after the exercise. These data suggest that acute exercise enhances the local bioactive androgen metabolism in the skeletal muscle of both sexes. ..
- Colciago A, Celotti F, Pravettoni A, Mornati O, Martini L, Negri Cesi P. Dimorphic expression of testosterone metabolizing enzymes in the hypothalamic area of developing rats. Brain Res Dev Brain Res. 2005;155:107-16 pubmed..It is concluded that rodent brain sexual differentiation probably involves the activation of both 5 alpha-R2 and aromatase enzymes in a sex- and time-specific pattern. ..
- Mahendroo M, Wilson J, Richardson J, Auchus R. Steroid 5alpha-reductase 1 promotes 5alpha-androstane-3alpha,17beta-diol synthesis in immature mouse testes by two pathways. Mol Cell Endocrinol. 2004;222:113-20 pubmed
- Klotsman M, Weinberg C, Davis K, Binnie C, Hartmann K. A case-based evaluation of SRD5A1, SRD5A2, AR, and ADRA1A as candidate genes for severity of BPH. Pharmacogenomics J. 2004;4:251-9 pubmed..polytomous logistic regression analysis was conducted to evaluate associations between two silent polymorphisms in SRD5A1 (codon positions 30 and 116), two polymorphisms in SRD5A2 (Val89Leu substitution and C to T transition in intron 1)..
- Thum T, Borlak J. Testosterone, cytochrome P450, and cardiac hypertrophy. FASEB J. 2002;16:1537-49 pubmed..We show alpha-MHC to be significantly repressed in cardiac hypertrophy and restored to normal on testosterone supplementation. We conclude that heart-specific steroid metabolism is of critical importance in cardiac hypertrophy ..
- Bhattacharyya A, Collins D. Site-directed mutagenesis studies of rat steroid 5alpha-reductase (isozyme-1): mutation of residues in the cofactor binding and C-terminal regions. J Steroid Biochem Mol Biol. 2001;77:177-82 pubmed
- Tsuruo Y, Ishimura K, Morita K. Influence of serum-free culture conditions on subcellular localization of steroid 5alpha-reductase in rat C6 glioma cells. Brain Res. 1998;801:130-6 pubmed
- Andersson S, Russell D. Structural and biochemical properties of cloned and expressed human and rat steroid 5 alpha-reductases. Proc Natl Acad Sci U S A. 1990;87:3640-4 pubmed..However, synthetic 4-azasteroids demonstrated marked differences in their abilities to inhibit the human and rat steroid 5 alpha-reductases. ..
- Patte Mensah C, Penning T, Mensah Nyagan A. Anatomical and cellular localization of neuroactive 5 alpha/3 alpha-reduced steroid-synthesizing enzymes in the spinal cord. J Comp Neurol. 2004;477:286-99 pubmed..These results are the first demonstrating that oligodendrocytes and neurons of the SC possess the key enzymatic complex for synthesizing potent neuroactive steroids that may control spinal sensorimotor processes. ..