5-alpha-reductase deficiency
Encyclopedia
5-Alpha-reductase deficiency (5-ARD) is an autosomal recessive intersex condition caused by a mutation of the 5-alpha reductase
type 2 gene
.
that converts testosterone
to dihydrotestosterone
(DHT) in peripheral tissues. 5-Alpha-reductase deficiency-2 is biochemically characterized by low to low-normal levels of testosterone and decreased levels of 5α-DHT, creating a higher testosterone/DHT ratio.
DHT is a potent androgen
, necessary for the development of male external genitalia in utero.
) because DHT has no known role in female development.
Individuals with 5-ARD can have normal male external genitalia, ambiguous genitalia, or normal female genitalia. They are born with male
gonad
s, including testicles and Wolffian structures
, but usually have female
primary sex characteristics. As a consequence, they are often raised as girls, but usually have a male gender identity
.
In general, individuals with 5-ARD are capable of producing viable sperm
. In individuals with feminized or ambiguous genitalia, there is a tendency towards a macroclitoris
or microphallus, and the urethra
may attach to the phallus. This structure may be capable of ejaculations as well as erections, but may be insufficient for intercourse
.
At puberty
, individuals often have primary amenorrhoea
, and may experience virilization
. This may include descending of the testes, hirsutism
(facial/body hair considered normal in males - not to be confused with hypertrichosis
), deepening of the voice, and enlargement of the clitoris. In adulthood, individuals do not experience male-pattern baldness. As DHT is a far more potent androgen than testosterone alone, virilization in those lacking DHT may be absent or reduced compared to males with functional 5-alpha reductase. It is hypothesized that rising testosterone levels at the start of puberty (around age twelve) are able to generate sufficient levels of DHT either by the action of 5-alpha-reductase type 1 (active in the adult liver, non-genital skin and some brain areas) or through the expression of low levels of 5-alpha-reductase type 2 in the testes.
in 5-ARD, causing infertility, but also a higher risk of testicular cancer
. Fertility is further compromised by the underdevelopment of seminal vesicles and prostate.
On the other hand, fertility depending on female characteristics is impossible; although the external genitalia may be female, the vagina consists of only the lower two-thirds of a normal vagina, creating a blind-ending vaginal pouch. Due to the normal action of Müllerian inhibiting factor
produced by the testes in utero, individuals with 5-ARD lack a uterus
and Fallopian tube
s. Thus, individuals with 5-ARD are not able to carry a pregnancy, and, since they have testes and not ovaries, they are unable to create ova, which precludes such infertility treatments as surrogate motherhood.
5-alpha reductase
5α-reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in 3 metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism, and prostate cancer....
type 2 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...
.
Normal function
5-Alpha-reductase is an enzymeEnzyme
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 converts 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...
to 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) in peripheral tissues. 5-Alpha-reductase deficiency-2 is biochemically characterized by low to low-normal levels of testosterone and decreased levels of 5α-DHT, creating a higher testosterone/DHT ratio.
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...
, necessary for the development of male external genitalia in utero.
Signs
The condition affects only genetic males (that is, those with a Y-chromosomeY chromosome
The Y chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y chromosome is composed of about 60 million base pairs...
) because DHT has no known role in female development.
Individuals with 5-ARD can have normal male external genitalia, ambiguous genitalia, or normal female genitalia. They are born with male
Male
Male refers to the biological sex of an organism, or part of an organism, which produces small mobile gametes, called spermatozoa. Each spermatozoon can fuse with a larger female gamete or ovum, in the process of fertilization...
gonad
Gonad
The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. The product, gametes, are haploid germ cells. For example, spermatozoon and egg cells are gametes...
s, including testicles and Wolffian structures
Wolffian structures
In anatomy, Wolffian structures are male urogenital structures that include the epididymis, vas deferens, and seminal vesicles. They are often referred to in cases of androgen insensitivity syndrome.-See also:...
, but usually have female
Female
Female is the sex of an organism, or a part of an organism, which produces non-mobile ova .- Defining characteristics :The ova are defined as the larger gametes in a heterogamous reproduction system, while the smaller, usually motile gamete, the spermatozoon, is produced by the male...
primary sex characteristics. As a consequence, they are often raised as girls, but usually have a male gender identity
Gender identity
A gender identity is the way in which an individual self-identifies with a gender category, for example, as being either a man or a woman, or in some cases being neither, which can be distinct from biological sex. Basic gender identity is usually formed by age three and is extremely difficult to...
.
In general, individuals with 5-ARD are capable of producing viable sperm
Sperm
The term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...
. In individuals with feminized or ambiguous genitalia, there is a tendency towards a macroclitoris
Clitoromegaly
Clitoromegaly is an abnormal enlargement of the clitoris ....
or microphallus, and the urethra
Urethra
In anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine...
may attach to the phallus. This structure may be capable of ejaculations as well as erections, but may be insufficient for intercourse
Sexual intercourse
Sexual intercourse, also known as copulation or coitus, commonly refers to the act in which a male's penis enters a female's vagina for the purposes of sexual pleasure or reproduction. The entities may be of opposite sexes, or they may be hermaphroditic, as is the case with snails...
.
At puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
, individuals often have primary amenorrhoea
Amenorrhoea
Amenorrhoea , amenorrhea , or amenorrhœa, is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen during pregnancy and lactation , the latter also forming the basis of a form of contraception known as the lactational amenorrhoea method...
, and may experience virilization
Virilization
In biology and medicine, virilization refers to the biological development of sex differences, changes that make a male body different from a female body. Most of the changes of virilization are produced by androgens...
. This may include descending of the testes, hirsutism
Hirsutism
Hirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
(facial/body hair considered normal in males - not to be confused with hypertrichosis
Hypertrichosis
Hypertrichosis is an abnormal amount of hair growth on the body; extensive cases of hypertrichosis have informally been called werewolf syndrome. There are two distinct types of hypertrichosis: generalized hypertrichosis, which occurs over the entire body, and localized hypertrichosis, which is...
), deepening of the voice, and enlargement of the clitoris. In adulthood, individuals do not experience male-pattern baldness. As DHT is a far more potent androgen than testosterone alone, virilization in those lacking DHT may be absent or reduced compared to males with functional 5-alpha reductase. It is hypothesized that rising testosterone levels at the start of puberty (around age twelve) are able to generate sufficient levels of DHT either by the action of 5-alpha-reductase type 1 (active in the adult liver, non-genital skin and some brain areas) or through the expression of low levels of 5-alpha-reductase type 2 in the testes.
Infertility
There is an increased risk of cryptorchidismCryptorchidism
Cryptorchidism is the absence of one or both testes from the scrotum. It is the most common birth defect regarding male genitalia. In unique cases, cryptorchidism can develop later in life, often as late as young adulthood. About 3% of full-term and 30% of premature infant boys are born with at...
in 5-ARD, causing infertility, but also a higher risk of testicular cancer
Testicular cancer
Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system.In the United States, between 7,500 and 8,000 diagnoses of testicular cancer are made each year. In the UK, approximately 2,000 men are diagnosed each year. Over his lifetime, a man's risk of...
. Fertility is further compromised by the underdevelopment of seminal vesicles and prostate.
On the other hand, fertility depending on female characteristics is impossible; although the external genitalia may be female, the vagina consists of only the lower two-thirds of a normal vagina, creating a blind-ending vaginal pouch. Due to the normal action of Müllerian inhibiting factor
Anti-müllerian hormone
Anti-Müllerian hormone also known as AMH is a protein that, in humans, is encoded by the AMH gene. It inhibits the development of the Müllerian ducts in the male embryo. It has also been called Müllerian inhibiting factor , Müllerian-inhibiting hormone , and Müllerian-inhibiting substance...
produced by the testes in utero, individuals with 5-ARD lack a uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
and Fallopian tube
Fallopian tube
The Fallopian tubes, also known as oviducts, uterine tubes, and salpinges are two very fine tubes lined with ciliated epithelia, leading from the ovaries of female mammals into the uterus, via the utero-tubal junction...
s. Thus, individuals with 5-ARD are not able to carry a pregnancy, and, since they have testes and not ovaries, they are unable to create ova, which precludes such infertility treatments as surrogate motherhood.
Prevalence
The number of people with this condition varies relative to geographic location, depending on how much of a given population is interrelated. In 1974, Jullianne Imperato-McGinley has estimated an incidence of 1:90 males in the Dominican Republic.See also
- Intersexuality
- 17-beta-hydroxysteroid dehydrogenase deficiency17-beta-hydroxysteroid dehydrogenase deficiency17-beta-hydroxysteroid dehydrogenase III deficiency is a rare disorder of sexual development affecting testosterone biosynthesis, which can produce impaired virilization of genetically male infants and children and excessive virilization of female adults.It is an autosomal recessive condition and...
- Androgen insensitivity syndromeAndrogen insensitivity syndromeAndrogen insensitivity syndrome is a condition that results in the partial or complete inability of the cell to respond to androgens. The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as...
- Gonadal dysgenesisGonadal dysgenesisGonadal dysgenesis is a term used to describe multiple reproductive system development disorders. They are conditions of genetic origin. It is characterized by a progressive loss of primordial germ cells on the developing gonads of an embryo....
- Jeffrey EugenidesJeffrey EugenidesJeffrey Kent Eugenides is an American Pulitzer Prize-winning novelist and short story writer. Eugenides is most known for his first two novels, The Virgin Suicides and Middlesex . His novel The Marriage Plot was published in October, 2011.-Life and career:Eugenides was born in Detroit, Michigan,...
's Pulitzer PrizePulitzer PrizeThe Pulitzer Prize is a U.S. award for achievements in newspaper and online journalism, literature and musical composition. It was established by American publisher Joseph Pulitzer and is administered by Columbia University in New York City...
winning novel MiddlesexMiddlesex (novel)Middlesex is a Pulitzer Prize-winning novel by Jeffrey Eugenides published in 2002. The book is a bestseller, with more than three million copies sold as of May 2011. Its characters and events are loosely based on aspects of Eugenides' life and observations of his Greek heritage. It is...
External links
- OMIM article
- 5-Alpha-Reductase Deficiency at eMedicine
- "Whatever I feel..." Article in the New Internationalist
- "Guevote: The Way I Feel Is How I Am" A film by Rolando Sánchez