Hormonal Evaluation of a Large Kindred with Complete Androgen Insensitivity: Evidence for Secondary 5α-Reductase Deficiency*

Abstract

Seventeen individuals from a pedigree with complete androgen insensitivity, [testicular feminization (TF)] are presented. Their hormonal evaluation was compared with those of normal males and male pseudohermaphrodites with primary 5a-reductase deficiency. The mean plasma testosterone to dihydrotestosterone ratio was 12 ± 3 in normals, 24 ± 8 in TF subjects (P < 0.001), and 41 ± 14 (P < 0.001) in 5a-reductasedeficient subjects. In 4 TF subjects the MCRs for testosterone and dihydrotestosterone were normal. The dihydrotestosterone blood production rate averaged 383 jug/day in normals, 162 jig/ day in TF subjects, and 86 /ig/day in 5a-reductase-deficient subjects. The conversion ratio of testosterone to dihydrotestosterone averaged 2.53 in normals, 1.8 in TF subjects, and 0.63 in 5a-reductase-deficient subjects. The mean plasma estradiol level was 2.8 ± 1.0 ng/100 ml in normal males, 4.8 ± 1.3 ng/100 ml (P < 0.001) in TF subjects, and 3.1 ± 1.3 ng/100 ml (P < 0.5) in 5a-reductase-deficient subjects. The fractional plasma protein binding of testosterone in TF subjects and 5a-reductase-deficient subjects was similar to that in normal males. The mean urinary etiocholanolone to androsterone ratio was 0.87 ± 0.34 in normals, 1.28 ± 0.46 (P < 0.001) in TF subjects, and 4.90 ± 2.15 (P < 0.001) in 5a-reductase-deficient subjects. The mean urinary ratio of 5/?-tetrahydrocorticosterone to 5a-tetrahydrocorticosterone was 0.53 ± 0.22 in normal males, 0.76 ± 0.21 in TF subjects (P < 0.02), and 4.59 ± 4.5 (P < 0.001) in 5a-reductase-deficient subjects. The mean urinary 5/?-tetrahydrocortisol to 5a-tetrahydrocortisol ratio was in the normal male range in the TF subjects, but was markedly elevated in the 5a-reductase-deficient subjects. The data suggest that in the TF subjects, there is a decrease in peripheral 5a-reductase activity related to C-19 androgen 5a-metabolism, which is a secondary manifestation of androgen resistance. This differs from the situation in the male pseudohermaphrodites with 5a-reductase deficiency, where the defect affects hepatic and peripheral 5a-reduction with a marked decrease in both 5a C-19 and C-21 metabolites. (J Clin EndocrinolMetab 54: 931, 1982)

The Relationship between Sex Steroids and Sex-Hormone-Binding Globulin in Plasma in Physiological and Pathological Conditions

“…In addition, plasma oestradiol was elevated in the kindred reported by ImperatoMcGinley et at. 30 Thus in these two studies of patients with complete androgen insensitivity there is no evidence of increased sensitivity of plasma SHBG levels to oestrogens.…”

Sex as a Biological Variable: Who, What, When, Why, and How

“…Aromatization of testosterone to estradiol occurs in primates, including humans, but does not necessarily have a major role in masculinization of the primate brain. Instead, both testicular production of testosterone and intact androgen receptors are necessary to defeminize the human brain as evidenced by the feminine phenotype of XY individuals with complete androgen insensitivity syndrome and masculine phenotype of those with aromatase dysfunction (Imperato-McGinley et al, 1982;Grumbach and Auchus, 1999). Certainly, evidence in humans also suggests a strong correlation between fetal testosterone levels and steroidogenic activity with neurodevelopmental disease risk and adult cognitive and behavioral stress reactivity, supporting the importance of the processes involved in establishing the sexually dimorphic Figure 3 Sex and gender differences across the life span.…”

Androgen insensitivity syndrome: clinical features and molecular defects

“…Adults with in situ testes usually have increased levels of LH, normal (sometimes elevated) concentration of T and follicle-stimulated hormone (FSH) as compared to normal males, and estradiol at the upper normal limits. 51,64 In PAIS, hCG testing is necessary to demonstrate normal T and DHT production so as to exclude defects in testosterone biosynthesis and 5alpha-reductase 2 deficiency. High levels of LH result from a reduced sensitivity of the hypothalamus and hypophysis to the negative feedback regulation of gonadotropin secretion by sex steroids, probably due to impaired androgen sensitivity.…”