Estrogen Receptor-α and β are Differentially Distributed, Expressed and Activated in the Fetal Genital Tubercle

Abstract

This study provides in vivo evidence that estrogen receptor-alpha expression in the genital tubercles of each sex increases until parturition but estrogen receptor-beta expression does not, implying genital tubercle sensitivity to estrogen increases during fetal life. Exogenous administration of estrogens results in a response of increased expression of estrogen receptor-alpha but not of estrogen receptor-beta. These differential findings for estrogen receptor-alpha and beta imply that the 2 receptors may have different roles in normal or anomalous genital tubercle development.

Hypospadias: Interactions between environment and genetics

“…Molecular analyses in fetal rat testes after in utero exposure to phtalates have shed light on the potential mechanisms via which phtalates suppress testicular testosterone production. Several key genes involved in steroidogenesis were disrupted after in utero exposure to monobutyl phthalate and monoethyl hexyl phthalate, such as StAR, HMG-CoA synthase, SRB1 and the steroidogenic enzymes Exogenous administration of estrogens also results in an increased expression of ERα (but not ERβ) [110]. Expression of TGF-β1 is also modulated by endocrine disruptors.…”

Molecular mechanisms of induction of persistent changes by estrogenic chemicals on female reproductive tracts and external genitalia

“…In contrast, mechanisms of DES and other estrogens-induced external genitalia malformation has not been clarified. ERs are endogenously expressed in the embryonic external genitalia [93,106,107]. Further, ER␣ mutant mice are resistant to estrogens-induced penile abnormalities [108] indicating that estrogen-exposure could directly perturb male genitalia development.…”

Genetic pathway of external genitalia formation and molecular etiology of hypospadias

“…Estrogen receptors (ERs) ER alpha and beta are differentially distributed and activated in mouse fetal GT [50]. Ban et al reported that the G allele containing variants of ER alpha (ESR1) XbaI and the G allele containing variants of ER beta (ESR2) 2681-4A > G may decrease the risk of hypospadias, whereas the ESR1 C-A haplotype may increase the risk [51].…”