Androgen Binding in Cultured Human Fibroblasts from Patients with Idiopathic Hypospadias

Abstract

Androgens stimulate development and growth of the external male genitalia. Since hypospadias represents the most common congenital abnormality in the male newborn and the mechanism of action in this disorder is still unclear, androgen binding was assessed in cultured fibroblasts from biopsies from genital skin of 10 patients with idiopathic hypospadias. For comparison, binding was determined in corresponding samples from 8 males with normal penile development and from 9 patients with known androgen resistance syndromes (testicular feminization, Reifenstein syndrome, pseudovaginal perineoscrotal hypospadias). Finally, binding was measured in 10 samples of nongenital skin. Maximum specific binding (Bmax) in idiopathic hypospadias varied from 3.2 to 15.5 (median 6.6) fmol.mg protein-1. Bmax in samples of persons with normal genital development was between 12.2 and 17.9 fmol.mg protein-1 (median 13.2). Bmax in samples of patients with known androgen resistance syndromes was exactly in the range reported previously in the literature. It is evident that Bmax in samples of patients with idiopathic hypospadias differs significantly (P less than 0.01), (Mann Whitney U-test) from those with normal genital development. Thus it seems reasonable to conclude that in some patients with idiopathic hypospadias the genital defect is caused by receptor deficiency.

Intracellular and nuclear binding of [3H]dihydrotestosterone in cultured genital skin fibroblasts of patients with severe hypospadias.

“…Later, Keenan et al (16) reported a lower mean [3H]DHT binding in fibroblasts cultured from foreskin of 28 infants with simple idiopathic hypospadias as compared with a control group. Similar results have also been observed in our laboratory (17,18): in a group of 10 patients with idiopathic hypospadias, mean maximum specific binding of methyltrienolone in cultured genital skin fibroblasts was lower than in 8 males with normal penile development.…”

Spezifische Hemmung der 5α-Reduktase durch einen neuen Extrakt aus Sabal serrulata

“…Genitalhautfibroblasten wurden aus der Vorhaut eines 5 Jahre alten Jungen, der sich einer Zirkumzision wegen einer Phimose unterziehen mußte, kultiviert (Zellinie GS 211). Die Genitalhautfibroblasten wurden, wie zuvor beschrieben, kultiviert und aufbewahrt (16,17). (14).…”

Oestrogen formation in genital and non‐genital skin fibroblasts cultured from patients with hypospadias

“…In accord with this concept, several syndromes of hereditary male pseudohermaphroditism with hypospadias can result either from deficient testicular testosterone secretion or from resistance of target organs to the action of androgen. For example, testicular feminization and the Reifenstein syndrome, which are inherited as Xlinked traits, are caused by abnormalities of the intracellular androgen receptor protein (Wilson et al, 1983;Schweikert & Romalo, 1990;Griffin, 1992;Schweikert, 1993). These syndromes are rare; for instance, testicular feminization, the best studied of these disorders, occurs at a prevalence of 1 in 20000 to 1 in 60 000 male births (Wilson et al, 1983).…”

“…These syndromes are rare; for instance, testicular feminization, the best studied of these disorders, occurs at a prevalence of 1 in 20000 to 1 in 60 000 male births (Wilson et al, 1983). With regard to sporadic hypospadias only a small number of cases can be explained as the result of a defect in the androgen receptor (Svensson & Snochowski, 1979;Keenan et al, 1984;Schweikert et al, 1987Schweikert et al, , 1989.…”