Partial or complete inability of cells to respond to androgen hormones due to a mutation in the androgen receptor gene located on the X chromosome.
Not all AR mutations result in androgen insensitivity, this only occurs when other genetic factors are present.
– Major symptoms:
Genotypic makes presenting as phenotypic females, involving decreased masculinization of male genetalia, short vagina (if female), spermatogenic defects, regression of Mullerian structures, impaired conversion of testosterone to dihydrotestosterone.
Symptoms range from pseudohermaphroditism to normal male phenotype but infertility.
Androgenic Alopecia
– Pathway/Axis:
androgens (testosterone, DHT)
– Major cause:
Type II a-reductase activity at hair follicle coverts testosterone to DHT.
DHT binds to DHT receptors in the scalp and leads to decreased hair growth.
Increased activity of DHT receptors in the scalp leads to hair follicles to be more sensitive to DHT.
It can also be caused by hyperactive Type II 5 a-reductase. Decreased levels of sex hormone-binding globulin can also lead to more free testosterone available to be converted to DHT.
– Major symptoms:
In men- the gradual recession of frontal hairline, overtime, hairline recedes to form characteristic “M” shape, hair thins at the crown and often progresses to partial or complete baldness.
In women- hair becomes thinner all overhead, hairline does not recede
Aromatase deficiency
– Pathway/Axis:
HPG Axis/ Androgen steroidogenesis
– Major cause:
Loss-of-function mutation of the CYP19A1 gene encoding the aromatase enzyme causes a patient to lose the ability to convert androgens to estrogens in the estrogen steroidogenesis pathway.
Autosomal recessive inheritance.
– Major symptoms:
In females, patients are born with ambiguous external genitalia and rapidly develop ovarian cysts that prevent ovulation.
They also do not develop secondary sex characteristics in puberty.
All aromatase deficient patients suffer from hyperglycemia as well as abnormal bone growth causing bones to be long, thin, and osteoporotic due to slowed mineralization.
Kallman syndrome
– Pathway/Axis:
Hypothalamic/Pituitary/Gonads (HPG) Axis
– Major cause:
a form of HH, a condition affecting the production of hormones that direct sexual development.
Isolated deficiency of GnRH
– Major symptoms:
May not experience puberty or may experience incomplete puberty and symptoms of hypogonadism.
Men – decreased libido, erectile dysfunction, decreased muscle strength, and lack of aggressiveness and drive.
Women – dyspareunia and amenorrhea.
All patients have anosmia. fatigue, color blindness, hearing deficiency, and epilepsy.
Klinefelter syndrome
– Pathway/Axis:
testosterone (HPG) axis
– Major cause:
random genetic error, most commonly nondisjunction of sex chromosomes during meiotic divisions, that result in a male being born with an extra copy of the x chromosome.
Extra X chromosome leads to abnormal development of the testis which results in underproduction of testosterone and elevated levels of FSH.
– Major symptoms:
low testosterone (hypogonadism), enlarged breasts, small penis, weak bones, taller stature, and reduced muscle mass, facial hair, and body hair.
Infertility/sterility- little or no sperm production.
mutations in androgen receptors due to abnormal androgen receptor gene
– Major symptoms:
XY chromosomal male with female external genitalia (complete androgen insensitivity) or micropenis, gynecomastia, hypospadias (incomplete androgen insensitivity) but no ovaries, fallopian tubes, or uterus (testes are present in the abdomen); normal production of testosterone and conversion to dihydrotestosterone. No menstruation during puberty.
Hermaphrodites
True hermaphroditism
– Pathway/Axis:
HPG axis
– Major cause:
an individual has both testicular and ovarian tissue.
This can be caused by either SRY gene being expressed in one gonad but not the other or partial expression in the gonads during development
– Major symptoms:
ambiguous genitalia at birth, delayed or unexpected puberty, enlarged clitoris or micropenis, fused labia, or urethra opening is not in the correct position.
