3. 5-Reductase Deficiency

During fetal development, the genital tubercle, genital swellings, and genital folds masculinize when exposed to androgens. Androgens, or male hormones, are a general term for two specific hormones Ñ testosterone and dihydrotestosterone (DHT). DHT is a stronger androgen than testosterone, and DHT is formed when the enzyme 5-Reductase converts testosterone to DHT.

5- reductase enzyme
Testosterone	-----------a	Dihydrotestosterone

5-Reductase deficiency affects 46,XY individuals. During fetal development, the gonads differentiate into nomal testes, secrete appropriate amounts of testosterone, and patients are able to respond to this testosterone. However, affected individuals are unable to convert testosterone to DHT , and DHT is necessary for the external genitalia to masculinize normally. The result is a newborn baby with functioning testes, normally developed Wolffian ducts, no Mullerian ducts, a penis resembling a clitoris, and a
scrotum resembling labia majora.

At puberty, testosterone (not DHT), is the essential androgen for masculinization of the external genitalia. Therefore, stereotypical signs of masculine pubertal development will be observed in patients. These signs include an increase in muscle mass, lowering of the voice, growth of the penis (although it is unlikely that it will reach a normal male length), and sperm production if the testes remain intact. These patients have a fair amount of pubic or axillary hair growth, but they have little or no facial hair. They do not experience female breast development. The following chart illustrates the steps of sex differentiation associated with 5-Reductase Deficiency compared to those of unaffected males and females.

Normal Female Development	5-Reductase Deficiency	Normal Male Development
XX	XY	XY
ovaries develop	testes develop	testes develop
no androgen produced	testosterone but no DHT produced	androgen produced
Wolffian Ducts regress	Wolffian Ducts develop	Wolffian Ducts develop
no MIS produced	MIS produced	MIS produced
Mullerian Ducts develop	Mullerian Ducts regress	Mullerian Ducts regress
external genitalia are female	ambiguous external genitalia	external genitalia are male
feminizing puberty	testes left intact, partial masculinizing puberty OR feminizing puberty with removal of testes and estrogen therapy	masculinizing puberty