Male 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-... 

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. 

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... 

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... 

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. 

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

Wilson, J.D., Harrod, M.J., Goldstein, J.L., Hemsell, D.L. and MacDonald, P.C. (1974) Familial incomplete male pseudohermaphroditism, type 1. Evidence for androgen resistance and variable clinical manifestations in a family with the Reifenstein syndrome. The New England Journal of Medicine, 290, 1097-1103. 

J9. Jost, A., Testicular structure in hypogonadal states (remarks concerning the testes of male pseudohermaphrodites). Excerpta Med. Intern. Congr. Ser. 83, 1291-1292 (1964). 

F. Z. Stanczyk, and M. Zachmann (1983). Male pseudohermaphroditism due to 17,20-desmolase deficiency. J. Clin. Endocrinol. Metah. 57, 32-36. 

In the male, the penis is enlarged and may reach adult sizes at a very early age. The scrotum, the prostate, and the seminal vesicles develop precociously. The hair of the beard, the axillary regions, and the pubis grows in infancy. The general body growth of the child is accelerated, yet the adult male pseudohermaphrodite is usually shorter than normal because the epiphysis closes prematurely in patients with excess androgens. 17-Ketosteroid secretion in the urine is markedly elevated, but it can be normalized rapidly by the administration of small doses of cortisone. 

Tager, H.S., Steiner, D.F. Peptide hormones. In Annual review of biochemistry (Snell, E.E., Boyer, P.D., Meister, A., and Richardson, C.C., eds), vol. 43, p. 509-538. Palo Alto, Calif Annual Reviews Inc. 1974 Wilson, J.D., Harrod, M.J., Goldstein, J.L., Hemsell, D.L., MacDonald, P.C. Familial incomplete male pseudohermaphroditism, type 1. Evidence for androgen resistance and variable clinical manifestations in a family with the Reifenstein syndrome. New Engl. J. Med. 290, 1097-1103 (1974)... 

Fig. 29.4. Diagnosis of steroidogenic defects. For initial screening of intersexuality see Fig. 26.3. Other female pseudohermaphroditism. 180H-B 18-hydroxycorticosterone. Male pseudohermaphroditism.

McPhaul MJ, Griffin JE. Male pseudohermaphroditism caused by mutations in the human androgen receptor. J Clin Endocrinol Metab 84 3435-3441, 1999... 

Curry CJ, Carey JC, Holland JS, Chopra D, Fineman R, Golabi M, Sherman S, Pagon RA, Allanson J, Shulman S, Barr M, McGravey V, Dabiri C, Schimke N, Ives E, Hall BD. Smith-Lemli-Opitz syndrome-type II multiple congenital anomalies with male pseudohermaphroditism and frequent early lethality. Am J Med Genet 1987 26(1) 45. 

Further reading Wilson, J.D. and Macdonald, P.C. (1978). Male pseudohermaphroditism due to androgen resistance Testicular feminization and related syndromes. In Stan-bury, J.B., Wyngaarden, J.B. and Fredrickson, D.S. (eds.) The Metabolic Basis of Inherited Disease. 4th Edn., p. 894. (New York McGraw-Hill)... 

XY disorder of sex development with ambiguous genitalia (former male pseudohermaphroditism) is most frequently caused by an abnormal plasma testosterone level or an abnormal testosterone response. The most common causes are disorders in androgen synthesis or action. 

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