ESTROGEN FORMATION IN GENITAL AND NON-GENITAL SKIN FIBROBLASTS CULTURED FROM PATIENTS WITH HYPOSPADIAS

OBJECTIVE Hypospadias is the most common birth defect in males. In mos t cases the aetiology is unknown. Since penile development is androgen dependent and oestrogen can modify androgen action, we compared the f ormation of oestrogen in penile tissue from patients with hypospadias to those with normal penile development. DESIGN AND PATIENTS Oestrogen formation was assessed in fibroblast monolayers grown from biopsies o f genital and non-genital skin from 11 males with normal genital devel opment (controls) and 18 severe hypospadias utilizing the incorporatio n tritium into H2O resulting from the aromatization of 1 beta-H-3-andr ostenedione. RESULTS In paired fibroblast strains from genital and non -genital skin of nine males with hypospadias, oestrogen formation was significantly (P < 0.025) lower in nongenital skin. Rates of oestrogen formation were also higher in a subset of foreskins from subjects wit h hypospadias than in normal controls and the remaining hypospadias su bjects. In addition, oestrogen formation in this subset of fibroblast strains from patients with hypospadias was markedly enhanced by incuba tion of intact monolayers with either cholera toxin or forskolin, agen ts known to stimulate cAMP formation. Oestrogen formation in the remai ning cell strains (controls and hypospadias) was also enhanced in most instances by cholera toxin and forskolin, although to a much lower de gree. Thus, we identified in the hypospadias group a subgroup of fibro blast strains in which unstimulated and stimulated oestrogen formation was markedly higher than in other strains examined. CONCLUSIONS Since oestrogen can modify certain androgen effects within cells and since formation of the male genitalia during embryogenesis is mediated by an drogens, elevated oestrogen formation in male genital tissue might be a causative factor of hypospadias in some instances.