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

Abstract

Since oestrogen can modify certain androgen effects within cells and since formation of the male genitalia during embryogenesis is mediated by androgens, elevated oestrogen formation in male genital tissue might be a causative factor of hypospadias in some instances.

Clinical and biochemical investigations and molecular analysis of subjects with mutations in the androgen receptor gene

“…The screening for AR gene mutations is obviously not sufficient to fully understand the underlying defects of androgen insensitivity syndrome and one has to take into account the whole sequence of cellular events from uptake of the hormone to binding of the receptor to hormone responsive elements. Not even this might be sufficient since at least in some cases of androgen insensitivity syndrome, the balance of androgens with other hormones, especially oestrogens, might be important for a certain morphogenetic process as already suggested (Schweikert et al, 1976;Pinsky et al, 1992;Staib et al, 1994).…”

Genetic pathway of external genitalia formation and molecular etiology of hypospadias

“…Although male external genitalia formation is mediated by androgens, estrogen can modify these androgen effects. Elevated estrogen formation in male genital tissue might be a causative or risk factor for hypospadias [48]. There is an increased risk of hypospadias in the sons of women exposed to diethylstilbestrol, a potent synthetic estrogen, in utero [49].…”

The Genetic and Environmental Factors Underlying Hypospadias

“…A novel homozygous mutation has recently been described to cause aromatase deficiency in a 46,XX newborn (with enlarged GT and fusion of labioscrotal folds) and hypospadias and cryptorchidism in the 46,XY sibling [Bouchoucha et al, 2014]. Like reduced testosterone levels, elevated oestrogen levels may also be a risk factor for hypospadias [Staib et al, 1994]. The source of oestrogen can be external, and the risk of hypospadias increases in male babies of women exposed to diethylstilbestrol, a potent synthetic oestrogen, while in utero [Klip et al, 2002].…”