An Explanation for the Target Organ Unresponsiveness to Testosterone in the Testicular Feminization Syndrome

Northcutt, Robert C.; Island, Donald P.; Liddle, Grant W.

doi:10.1210/jcem-29-3-422

Cited by 93 publications

(20 citation statements)

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“…The acetates of dihydrotestosterone, etiocholanolone, and isoandrosterone are more difficult to separate than the free compounds. A contamination of dihydrotestosterone with other metabolites of testosterone and androstenedione could partially explain the similar MCRDHT values found by Mahoudeau and ourselves and the discordance in the values for the (p) BBETDHT and (pD) EBDET Studies made in vivo and in vitro suggest that the conversion of testosterone into dihydrotestosterone by the target organs is reduced in the testicular feminization syndrome (32)(33)(34)(35). In the three patients with this syndrome the over-all conversion of testosterone into dihydrotestosterone was within the limits for males.…”

Section: Mcra Mcrt Mcrdht A-14c/t-14c T-$h/aand-sh Dht-14c/t-14c Dht-5hsupporting

confidence: 54%

Metabolic clearance rate and blood production rate of testosterone and dihydrotestosterone in normal subjects, during pregnancy, and in hyperthyroidism

Saez¹,

Forest²,

Morera³

et al. 1972

J. Clin. Invest.

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A B S T R A C T The metabolic clearance rate (MCR) and blood production rate (BP) of testosterone (T) and dihydrotestosterone (DHT), the conversion of plasma testosterone to plasma dihydrotestosterone, and the renal clearance of androstenedione, testosterone, and dihydrotestosterone have been studied in man. In eight normal men, the MCRT (516±108 [SD] liters/m/day) was significantly greater than the MCRDIT (391±71 [SD] liters/m'/day). In seven females, the MCRT (304±53 [SD] liters/m'/day) was also greater than the MCRDET (209±45 [SD] liters/ m2/day) and both values were less than their respective values in men (P <0.001). In men the conversion of testosterone into dihydrotestosterone at 2.8±0.3% (SD) was greater than that found in females, 1.56±0.5% (SD) (P < 0.001). In five pregnant females the MCRT (192± 36 [SD] liters/m/day), the MCRDHT (89±30 [SD] liters/ m'/day) and the conversion of testosterone into dihydrotestosterone (0.72±0.15%) (SD) were significantly less than the values found in nonpregnant women. In five females with hyperthyroidism, the MCR for testosterone and dihydrotestosterone were similar to those observed in pregnant females, but the conversion of testosterone into dihydrotestosterone (2.78±1.7%) (SD) was greater, and similar to that found in men. In men the production of dihydrotestosterone was 0.39±0.1 (SD) mg/day, 50% being derived from the transformation of plasma testosterone. In women the production of DHT was 0.05± 0.028 (SD) mg/day, only 10% coming from testosterone. During pregnancy, the production of testosterone and dihydrotestosterone are similar to that in normal women. In three patients with testicular feminization syndrome A preliminary report of this work was presented at the 52nd Meeting of the Endocrine Society, June 1970.Received for publication 24 August 1971 and in revised form 20 December 1971. (an adult with hyperthyroidism and two children) these two MCRs were greatly reduced compared to the normal females, but the conversion of testosterone into dihydrotestosterone was in the limits of normal male rangeIn the normal subjects the renal clearance of androstenedione was greater than that of testosterone and dihydrotestosterone. Less than 20% of the dihydrotestosterone and less than 10% of the androstenedione in the urine is derived from the plasma dihydrotestosterone and androstenedione.

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Section: Mcra Mcrt Mcrdht A-14c/t-14c T-$h/aand-sh Dht-14c/t-14c Dht-5hsupporting

confidence: 54%

Metabolic clearance rate and blood production rate of testosterone and dihydrotestosterone in normal subjects, during pregnancy, and in hyperthyroidism

Saez¹,

Forest²,

Morera³

et al. 1972

J. Clin. Invest.

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“…The findings in the present study that dihydrotestosterone formation was normal in the anlage of the male organs of accessory reproduction at birth may have implications for the interpretation of the pathogenesis of the human variety of the disease, where it has been reported that dihydrotestosterone formation is deficient in the perineal skin and other tissues (14)(15)(16). On the basis of the present study it is clear that deficient dihydrotestosterone formation in human testicular feminization could result either from a defect that involves primarily the enzyme that performs this conversion or from a developmental defect that prevents the differentiation of the cell lines that contain this enzymatic function.…”

Section: Estismentioning

confidence: 52%

“…In keeping with this hypothesis, a number of recent studies have appeared attempting to explain the biochemical basis of the androgen resistance in testicular feminization. For example, in testicular feminization in man the conversion of testosterone to its active derivative dihydrotestosterone is deficient in perineal skin (14)(15)(16). In affected rats (17) and in affected mice (18,19) it has been reported that the intracellular binding of androgen in target tissues, such as the preputial gland and the kidney, is diminished despite normal rates of dihydrotestosterone formation.…”

Section: Introductionmentioning

confidence: 99%

Studies on the pathogenesis of the pseudohermaphroditism in the mouse with testicular feminization

Goldstein¹,

Wilson²

1972

J. Clin. Invest.

151

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“…Wilson and Walker (6) demonstrated a decreased conversion of testosterone to dihydrotestosterone in skin slices from the labia majora of patients with testicular feminization. Northcutt, Island, and Liddle (7) found that the amount of dihydrotestosterone formed by slices of suprapubic skin was lower in testicular feminization patients than in normal males. The mother of one of their testicular feminization patients could not be distinguished from a normal female when the reduction of testosterone to dihydrotestosterone by suprapubic skin slices was compared.…”

Section: Introductionmentioning

confidence: 99%

Metabolism of testosterone-14C by cultured human cells

Shanie¹,

Hirschhorn²,

New³

1972

J. Clin. Invest.

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A B S T R A C T The metabolism of "C-labeled testosterone by cultured human fibroblasts and amniotic fluid cells was investigated. Radiolabeled testosterone was incubated with the cultured cells for 48 hr, and the labeled metabolites present in the medium were subsequently identified. The major metabolic products of testosterone formed by cultured fibroblasts were A'-androstenedione, dihydrotestosterone, androsterone, and androstanediol. The amount of testosterone metabolized through each of two pathways was calculated and used to form a ratio designated the 17f-hydroxyl/17-ketonic ratio. Fibroblasts from normal male and female children and adult females had high 17P-hydroxyl/17-ketonic ratios indicating testosterone metabolism occurred primarily through the 17P-hydroxyl pathway. There was a change in the pattern of testosterone metabolism with age in males, i.e., adult males had much lower 17#-hydroxyl/17-ketonic ratios than did male children.The testosterone metabolism of fibroblast cultures derived from three children with testicular feminization and their mothers was compared to normal age and sexmatched controls. Fibroblasts of children with testicular feminization metabolized testosterone predominantly through the 17-ketonic pathway and manifested a pattern of testosterone metabolism distinctly different from their sex and age matched controls. The mothers of children with testicular feminization could be distinguished from normal females by their much lower 17#-hydroxyl/17-ketonic ratios. The much lower amounts of dihydrotestosterone and androstanediol produced by fibroblasts from patients with testicular feminization as

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An Explanation for the Target Organ Unresponsiveness to Testosterone in the Testicular Feminization Syndrome

Cited by 93 publications

References 0 publications

Metabolic clearance rate and blood production rate of testosterone and dihydrotestosterone in normal subjects, during pregnancy, and in hyperthyroidism

Metabolic clearance rate and blood production rate of testosterone and dihydrotestosterone in normal subjects, during pregnancy, and in hyperthyroidism

Studies on the pathogenesis of the pseudohermaphroditism in the mouse with testicular feminization

Metabolism of testosterone-14C by cultured human cells

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