PRENATAL IN-VIVO BULBOURETHRAL GLAND DEVELOPMENT IS NOT AFFECTED BY PROSTAGLANDIN E(2) INHIBITION

Investigation of bulbourethral gland (BUG) development is useful to st udy genitourinary (GU) tract growth and differentiation. Understanding GU tract growth and differentiation is relevant to testing the hypoth esis that the initial lesion of human benign prostatic hyperplasia inv olves focal re-expression of inductive processes in the periurethral r egion of the prostatic transitional zone. Prostaglandins play a role i n regulating growth and morphogenesis of different organ systems. Prev ious reports have proposed that prostaglandin E(2) (PgE(2)) mediates t he masculinizing effects of testosterone in the developing neonatal ma le GU tract. We have previously shown that androgens lower rather than raise BUG PgE(2) levels. Further studies led us to conclude that PgE( 2) does not play a major role in postnatal BUG growth and morphogenesi s in vitro. In order to investigate the possible role of PgE(2) in pre natal BUG development, indomethacin (INDO, 1.0 mg/kg- day, subcutaneou sly) was administered to pregnant BALB/c mice on gestational days 12-1 8. Control pregnant mice were either untreated or injected with dimeth ylsulfoxide vehicle. Anogenital distances were measured within 12 hour s after birth in male and female offspring on day 19. In male neonatal mice, BUGs were examined histologically and PgE(2) levels were measur ed by radioimmunoassay in BUGs and whole genital tracts. We observed n o significant morphological differences in INDO-exposed BUGs compared to controls. No significant differences in mean anogenital distances o f INDO-exposed male offspring or controls were detected. Mean anogenit al distances of female offspring were similar in the three respective groups. Mean BUG PgE(2) levels in INDO-exposed neonates were significa ntly lower (P < 0.05) than in untreated neonates. Significant (P < 0.0 5) PgE(2) inhibition by prenatal INDO treatment was also detected in b oth female and male GU tracts, confirming effective blockade of PgE(2) production by INDO. We conclude that although INDO effectively inhibi ts PgE(2) production, it has no effect on antenatal BUG development. C ontrary to previous reports, we were unable to detect significant decr eases in anogenital distances of INDO-exposed neonatal males. Further understanding of the role of steroid hormones and prostaglandin metabo lism using in vitro and in vivo animal models such as the BUG system m ay yield insight into human developmental and proliferative GU tract d isorders.