Syndromes of Abnormal Sex Differentiation - Develop Both Male and Female Characteristics

Written by Berdache Jordan

Page 8 of 14

4. Testosterone Biosynthetic Defects

Testosterone is produced from cholesterol through a number of biochemical conversions. In some individuals, one of the enzymes needed for these conversions is deficient. In such cases, patients are unable to make normal amounts of testosterone despite the presence of testes. Testosterone Biosynthetic Defects affect 46,XY individuals and can be complete or partial, which leads to newborns who appear either completely female or ambiguous, respectively. Four Testosterone Biosynthetic Defects are

listed below:

Cytochrome P450,CYP11A Deficiency
3B-Hydroxysteroid Dehydrogenase Deficiency
Cytochrome P450,CYP17 Deficiency
17-Ketosteroid Reductase Deficiency

The first three enzyme deficiencies listed above result in Congenital Adrenal Hyperplasia (CAH) (described later) as well as decreased testosterone production by the testes. The fourth enzyme, 17-Ketosteroid Reductase Deficiency, is not associated with CAH. The following chart illustrates the steps of sex differentiation associated with Testosterone Biosynthetic Defects compared to those of unaffected males and females.

Complete Biosynthetic Defect

Normal Female Development	Complete Testosterone Biosynthetic Defect	Normal Male Development
XX	XY	XY
ovaries develop	testes develop	testes develop
no androgen produced	no androgens due to enzyme deficiency	androgen produced
Wolffian Ducts regress	Wolffian Ducts regress	Wolffian Ducts develop
no MIS is produced	MIS is produced	MIS is produced
Mullerian Ducts develop	Mullerian Ducts regress	Mullerian Ducts regress
external genitalia are female	external genitalia are female	external genitalia are male
feminizing puberty	feminizing puberty if given estrogen therapy	masculinizing puberty

Partial Biosynthetic Defect

Normal Female Development	Partial Testosterone Biosynthetic Defect	Normal Male Development
XX	XY	XY
ovaries develop	testes develop	testes develop
no androgen produced	partial production of androgens	androgen produced
Wolffian Ducts regress	some Wolffian Duct development	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	partial masculinizing puberty with testosterone therapy OR feminizing puberty with estrogen therapy	masculinizing puberty