Pseudohermaphroditism

Testosterone, the principal male sex steroid hormone, is synthesized in five steps from cholesterol, as shown below. In the last step, five isozymes catalyze the 17/3-hydroxysteroid dehydrogenase reactions that interconvert 4-androstenedione and testosterone. Defects in the synthesis or action of testosterone can impair the development of the male phenotype during embryogenesis and cause the disorders of human sexuality termed male pseudohermaphroditism. Specifically, mutations in isozyme 3 of the 17/3-hydroxysteroid dehydrogenase in the fetal testis impair the for-... 

Evidence that BPH could be hormone related came from studies of a population of pseudohermaphrodites in the Dominican Republic. These individuals are genetically male, but do not display normal male genitalia until the onset of puberty. They are therefore raised as females until puberty. Studies revealed that these pseudohermaphrodites are deficient in an isoform of the enzyme steroid 5a-reductase, which is responsible for catalyzing the conversion of testosterone to dihydrotestosterone (DHT). In addition to the overt sexual manifestations of this condition, affected individuals show no incident of male pattern baldness, mild or no acne, and underdevelopment of the prostate. These observations led researchers to postulate that a selective inhibitor of steroid 5a-reductase would be an effective treatment for BPH. 

GromoU, J., Schulz, A., Borta, H., et al. (2002) Homozygous mutation within the conserved Ala-Phe-Asn-Glu-Thr motif of exon 7 of the LH receptor causes male pseudohermaphroditism. Eur. J. Endocrinol. 147, 597-608. 

Mendonca BB, Leite MV, de Castro M, et al. (2002) Female pseudohermaphroditism caused by a novel homozygous missense mutation of the GR gene. J Clin Endocrinol Metab. 87, 1805-1809. 

A male pseudohermaphrodite is the central subject of the Pulitzer Prize winning novel Middlesex by Jeffrey Eugenides. 

Deficiency of 5a-reductase-2 (5 -RD-2) is an important cause of male pseudohermaphroditism (MPH). It is occasionally found in large isolated kindreds, such as one studied in the Dominican Republic where the disorder was first detected [35] more recently, extended families from Turkey and New Guinea have been studied. 

Geissler WM, Davis DL, Wu L, Bradshaw KD, Patel S, Mendonca BB, Elliston , Wilson JD, Russell DW, Andersson S (1994) Male pseudohermaphroditism caused by mutations of testicular 17/ -hydroxysteroid dehydrogenase 3. Nat Genet 7 34-39... 

Imperato-McGinley J, Peterson RE, Gautier T, Arthur A, Shackleton C (1985) Decreased urinary C19 and C21 steroid 5a-metabolites in parents of male pseudohermaphrodites with 5a-reductase deficiency detection of carriers. J Clin Endocrinol Metab 60 553-558... 

Mendonca BB, Russell AJ, Vasconcelos-Leite M, Arnhold IJ, Bloise W, Wajchenberg BL, Nico-lau W, Sutcliffe RG, Wallace AM (1994) Mutation in 3/1-hydroxysteroid dehydrogenase type II associated with pseudohermaphroditism in males and premature pubarche or cryptic expression in females. J Mol Endocrinol 12 119-122... 

Peterson RE, Imperato-McGinley, J, Gautier T, Shackleton C (1985) Male pseudohermaphroditism due to multiple defects in steroid-biosynthetic microsomal mixed-function oxidases. A new variant of congenital adrenal hyperplasia. N Engl J Med 313 1182-1191... 

Jenner, M.G., Pseudohermaphroditism in Ilyanassa obsoleta (Mollusca Neogastropoda), Science, 205, 1407, 1979. 

DEFICIENCY in uiero, results in failure of male genital development. Deficiency in childhood results in failure to develop secondary male characteristics. This may be due to castration or a hypofunctioning hypotlialamus. In male pseudohermaphroditism, there appears to be a defect in the cellular recognition proteins for androgens, so that androgens, while present, do not stimulate the formation of male characteristics. 

A deficiency of ll -hydroxylase is the second most common form of CAH, with an incidence of 1 per 100,000 births, and is associated with manifestations of virilization, elevated concentrations of plasma androstenedione and DHEA-S, and hypertension. The mineralocorticoid-induced hypertension is caused by an elevation of DOC 11-deoxycortisol concentrations are markedly raised in subjects with this enzyme defect,The major distinguishing characteristic of this disorder from 21-hydroxylase deficiency, besides the elevated plasma concentrations of 11-deoxycortisol, is hypertension elicited by the salt retention caused by increased concentrations of DOC, A deficiency of 3 -hydroxysteroid dehydrogenase-isomerase has been reported and leads to an elevation in the ratio of 17a-hydroxypregnenolone to that of 17a-hydroxyprogesterone and to an increased ratio of DHEA to androstenedione. In severe forms of this rare disorder, female infants have pseudohermaphroditism, and male infants present with incomplete masculinization. Patients with this disorder usually present in early infancy with complete adrenal insufficiency including salt wasting. A late-onset form has also been reported in patients with premature pubarche with hirsutism, acne, and menstrual irregularities. The... 

Steroid 5 a reductase deficiency in man An inherited form of male pseudohermaphroditism. Science 1974 186 1213-5. 

When the condition of 17a-hydroxylase deficiency occurs, the production of cortisol and sex steroids (except for progesterone) is impaired and the production of miner-alocorticoids increased (see Figure 51-4, Chapter 51). With tliis deficiency, plasma concentrations of corticosterone, 11 - deoxycorticosterone, progesterone, and pregnenolone are elevated. Boys exhibit pseudohermaphroditism and deficiency in development of secondary sex characteristics. 

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