Expression Of Endocrine-related Genes Research Articles

Diesel exhaust affects immunological action in the placentas of mice

We investigated the effect of diesel exhaust (DE) on pregnancy and fetal development in mice at day 14 postcoitum (pc) with a special focus on the placenta. The number of absorbed fetuses increased in groups exposed to DE, and congestion was observed in histological sections of placentas. During placental absorption expression of CYP1A1 mRNA decreased to undetectable levels, whereas expression of TNF alpha mRNA increased approximately twofold over that of the control. Levels of CYP1A1 mRNA in normal placentas from DE-exposed mice were unchanged. mRNA levels of inflammatory cytokines IL-2, IL-5, IL-12 alpha, IL-12 beta, and GM-CSF increased in placentas exposed to DE (0.3 and 3.0 mg diesel exhaust particles (DEP)/m3). Expression of IL-5 mRNA was markedly increased in DE-exposed placentas, although levels were barely detectable in control placentas. IL-6 mRNA expression was increased approximately 10-fold in placentas exposed to DE (3.0 mg DEP/m3). It has been reported that expression of mRNA encoding proteins involved in immune function in the placenta is increased during fetal absorption in mice. In the present study, expression of such mRNA by the placenta was increased by DE exposure. Because it is believed that expression of mRNA in the placenta also affects fetal development, DE may promote fetal absorption. These findings suggest that in mice exposure to DE affects fetal absorption and placental function by modifying expression of immune-related genes during early gestation and expression of endocrine-related genes during late gestation.

Aromatic Hydrocarbon Receptor Expression and Function in Liver of Hypophysectomized Male Rats

The aromatic hydrocarbon receptor (AHR) acts as a ligand-activated transcription factor that mediates many of the biological responses to aromatic hydrocarbons, such as 3-methylcholanthrene (MC) and 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD). Some toxic effects are thought to be the result of AHR-mediated changes in the expression of endocrine-related genes, such as the estrogen receptor and genes involved in cell growth and differentiation. Since little is known about endocrine factors that regulate AHR expression and function, we evaluated the effect of hypophysectomy (hypx) on these parameters in the liver of male rats. Cytosolic AHR immunoreactive protein was reduced in hypx rats to 61% of levels in sham-operated rats. Sucrose density gradient analysis of cytosolic AHR radioligand binding using a saturating concentration of [ 3H]TCDD showed that ligand binding was reduced in hypx rats to 31% of sham levels. TCDD showed similar potency for transforming cytosolic AHR from hypx and sham rats to a DNA-binding form; however, maximal AHR DNA-binding was reduced in hypx rats to 57% of sham levels, although this did not achieve statistical significance. These changes observed at the protein level were not accompanied by a corresponding decrease in hypx rats of mRNA for AHR or the AHR nuclear translocator. Despite this change in AHR protein level, hypx rats were not compromised in hepatic cytochrome P450 1A1 induction following in vivo administration of MC. These data indicate that the AHR signaling pathway is intact in hypx rats and that a pituitary factor regulates hepatic AHR expression at the protein level.