Suppression of fetal testicular cytochrome P450 17 by maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: A mechanism involving an initial effect on gonadotropin synthesis in the pituitary

Maternal exposure to dioxin reduces hypothalamic but not pituitary metabolome in fetal rats: a possible mechanism for a fetus-specific reduction in steroidogenesis

“…Our previous studies have suggested that TCDD reduces the production of pituitary LH in a fetus-specific fashion, and this is a trigger for damages not only to gonadal steroidogenesis in the fetal stages (Mutoh et al, 2006;Taketoh et al, 2007) but also sexual behavior at adulthood (Takeda et al, 2009). The reason why the reduced production of LH by TCDD is seen only in fetuses is largely unknown.…”

“…Our previous studies have revealed that a number of steroidogenic proteins in fetal rats are downregulated by maternal exposure to TCDD (Mutoh et al, 2006;Taketoh et al, 2007;Takeda et al, 2009). For example, when pregnant rats at gestational day (GD) 8 or 15 were treated with 1 µg/kg TCDD (p.o.…”

Maternal Exposure to Dioxin Imprints Sexual Immaturity of the Pups through Fixing the Status of the Reduced Expression of Hypothalamic Gonadotropin-Releasing Hormone

“…More specifically, treating pregnant Wistar rats at gestational day (GD) 15 with 1 mg/kg TCDD transiently reduces the expression of LH in both pituitary mRNA and circulating hormone levels during a period from GD20 to postnatal day (PND) 0 . In accordance with this, TCDD reduces the testicular expression of steroidogenic proteins, including steroidogenic acuteregulatory protein (StAR), a cholesterol-transporting protein associated with a rate-limiting process of steroidogenesis (Manna et al, 2009), and CYP17, an essential enzyme for sexsteroid biosynthesis (Payne and Youngblood, 1995), in late fetuses and early neonates (Mutoh et al, 2006;Taketoh et al, 2007;Takeda et al, 2009Takeda et al, , 2012. In one of the preceding studies, direct supplementation of equine chorionic gonadotropin (eCG), an LH-mimicking hormone, into the fetuses exposed to TCDD at GD15 restored not only the attenuated expression of fetal steroidogenic proteins but also the impairment of sexual behaviors after reaching maturity (Takeda et al, 2009).…”

“…Our previous studies demonstrated that maternal treatment with TCDD at the late gestational stage attenuates the pituitary production of luteinizing hormone (LH), a primary regulator of gonadal steroidogenesis, during the perinatal stage (Mutoh et al, 2006;Taketoh et al, 2007;Takeda et al, 2009Takeda et al, , 2011Takeda et al, , 2012Koga et al, 2012). More specifically, treating pregnant Wistar rats at gestational day (GD) 15 with 1 mg/kg TCDD transiently reduces the expression of LH in both pituitary mRNA and circulating hormone levels during a period from GD20 to postnatal day (PND) 0 .…”

“…Very confusingly, brain and sex differentiation must be in concert with various mechanisms in a target gene-, brain region-, and exposing timing-specific manner (Davies and Wilkinson, 2006;McCarthy, 2008). Because maternal exposure to TCDD damages testicular steroidogenesis during the critical period (Mutoh et al, 2006;Taketoh et al, 2007;Takeda et al, 2009Takeda et al, , 2012, it is conceivable that TCDD disturbs the normal development of the hypothalamus to imprint the abnormality of gene expression or neural structure, leading to the impairment of sexual maturation such as the acquisition of sexual behavior.…”