Disorders linked to insufficient androgen action in male children

Virilization of the external genitalia in the male fetus requires testoster one and dihydrotestosterone (DHT), which is formed from testosterone by the action of the enzyme, 5 alpha -reductase type 2 (5 alphaR-2), Mediation of the effects of both testosterone and DHT requires a functional androgen re ceptor (AR) located in the cytoplasmic compartment of target Cells. DHT (or testosterone) binding induces a conformational change which facilitates AR nuclear transport, phosphorylation and dimerization, ultimately regulating of the rate of transcription of androgen-dependent genes. Any event which impairs DHT formation (mutation within the 5aR-2 gene or 5aR-2 inhibitors) or normal function of the AR::(mutation in the AR gene, antiandrogens) may result in insufficient androgen action in the male fetus and in Subsequent undervirilization in the newborn. Hypospadias may be due to a defect in and rogen action due to mutation of the 5aR-2 or of the AR gene, Mutation of un identified genes is likely to underlie this displacement of the urethral me atus-from the tip to the ventral side of the phallus. An aetiological role for environmental chemical products has been postulated, since ethnic as we ll as geographical differences in the incidence of hypospadias have been no ted. Increasing evidence has been gathered indicating that widely used indu strial and agricultural chemicals have deleterious effects on normal male s exual differentiation. Cryptorchidism and micropenis may represent an inter sex phenotype, even if they are isolated, Aetiological factors include 5aR- 2 gene mutation, AR gene mutation or environmental hormonal disrupters. In conclusion, several phenotypes have been attributed to insufficient androge n action during fetal life. Whereas mutations in the 5aR-2 gene and AR gene are natural, attention should be focused on environmental endocrine disrup ters that are able to mimic steroid 5a-reductase deficiency or partial andr ogen insensitivity syndrome.