SRD5A1
Encyclopedia
3-oxo-5-alpha-steroid 4-dehydrogenase 1 is an enzyme
that in humans is encoded by the SRD5A1 gene
.
Steroid 5-alpha-reductase (EC 1.3.99.5) catalyzes the conversion of testosterone
into the more potent androgen
, dihydrotestosterone
(DHT). There are 2 isoforms of the enzyme
: SRD5A1 and SRD5A2
.
family members bind to ETS DNA-binding sites and both regulate their own expression and the transcription of a subset of genes that are dependent upon testicular luminal fluid factors, including Ggt_pr4, SRD5A1, and Gpx5.
6-month dietary vitamin E
(VE) deficiency in rats resulted in a twofold increase in the mRNA level of SRD5A1 gene and a twofold decrease in the mRNA level of GCLM gene but is not directly mediated by changes in promoter DNA methylation.
Insulin increases the expression of 5α-reductase type 1 mRNA via Akt signalling
suggest that elevated levels of 5α-reduced androgens seen in hyperinsulinemic conditions might be explained on the basis of a stimulatory effect of insulin on 5α-reductase in granulosa cells leading to impaired follicle growth and ovulation.
PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5 alpha-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS.
Progression to castration-resistant prostate cancer (CRPC) is accompanied by increased expression of SRD5A1 over SRD5A2
, which is otherwise the dominant isoenzyme expressed in the prostate. The dominant route of DHT synthesis in human CRPC bypasses testosterone, and instead requires 5α-reduction of androstenedione
by SRD5A1 to 5α-androstanedione, which is then converted to DHT
fuelling cancer growth.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the SRD5A1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Steroid 5-alpha-reductase (EC 1.3.99.5) catalyzes the conversion of testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
into the more potent androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
, dihydrotestosterone
Dihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
(DHT). There are 2 isoforms of the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
: SRD5A1 and SRD5A2
SRD5A2
3-oxo-5-alpha-steroid 4-dehydrogenase 2 is an enzyme that in humans is encoded by the SRD5A2 gene.Steroid 5-alpha reductase catalyzes the conversion of the male sex hormone testosterone into the more potent androgen, dihydrotestosterone....
.
Regulation
ETV4ETV4
ETS translocation variant 4 is a protein that in humans is encoded by the ETV4 gene....
family members bind to ETS DNA-binding sites and both regulate their own expression and the transcription of a subset of genes that are dependent upon testicular luminal fluid factors, including Ggt_pr4, SRD5A1, and Gpx5.
6-month dietary vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
(VE) deficiency in rats resulted in a twofold increase in the mRNA level of SRD5A1 gene and a twofold decrease in the mRNA level of GCLM gene but is not directly mediated by changes in promoter DNA methylation.
Insulin increases the expression of 5α-reductase type 1 mRNA via Akt signalling
Akt/PKB signaling pathway
The Akt/PKB signaling pathway is a pathway in cell signaling.Proteins involved include AKT and phosphoinositide 3-kinase .It can be associated with cancer....
suggest that elevated levels of 5α-reduced androgens seen in hyperinsulinemic conditions might be explained on the basis of a stimulatory effect of insulin on 5α-reductase in granulosa cells leading to impaired follicle growth and ovulation.
Clinical signficance
Hyperinsulemia acutely enhances ACTH effects on both the androgen and glucocorticoid pathways leading to changes in steroid metabolites molar ratios that suggest insulin stimulation of 5 α-reductase activity.PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5 alpha-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS.
Progression to castration-resistant prostate cancer (CRPC) is accompanied by increased expression of SRD5A1 over SRD5A2
SRD5A2
3-oxo-5-alpha-steroid 4-dehydrogenase 2 is an enzyme that in humans is encoded by the SRD5A2 gene.Steroid 5-alpha reductase catalyzes the conversion of the male sex hormone testosterone into the more potent androgen, dihydrotestosterone....
, which is otherwise the dominant isoenzyme expressed in the prostate. The dominant route of DHT synthesis in human CRPC bypasses testosterone, and instead requires 5α-reduction of androstenedione
Androstenedione
Androstenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.-Synthesis:Androstenedione is the common precursor of male and female sex...
by SRD5A1 to 5α-androstanedione, which is then converted to DHT
DHT
-Science and technology:* Dihydrotestosterone, a potent endogenous androgenic hormone, derived from testosterone* Directly heated triode, a type of thermionic valve now used primarily in audio amplifiers...
fuelling cancer growth.