Yoshiaki Fujii

Human arylhydrocarbon receptor repressor (AHRR) gene: genomic structure and analysis of polymorphism in endometriosis

AbstractThe diversity of biological effects resulting from exposure to dioxin may reflect the ability of this environmental pollutant to alter gene expression by binding to the arylhydrocarbon receptor (AHR) gene and related genes. AHR function may be regulated by structural variations in AHR itself, in the AHR repressor (AHRR), in the AHR nuclear translocator (ARNT), or in AHR target molecules such as cytochrome P-4501A1 (CYP1A1) and glutathione S-transferase. Analysis of the genomic organization of AHRR revealed an open reading frame consisting of a 2094-bp mRNA encoded by ten exons. We found one novel polymorphism, a substitution of Ala by Pro at codon 185 (GCC to CCC), in exon 5 of the AHRR gene; among 108 healthy unrelated Japanese women, genotypes Ala/Ala, Ala/Pro, and Pro/Pro were represented, respectively, by 20 (18.5%), 49 (45.4%), and 39 (36.1%) individuals. We did not detect previously published polymorphisms of ARNT (D511N) or the CYP1A1 promoter (G-469A and C-459T) in our subjects, suggesting that these polymorphisms are rare in the Japanese population. No association was found between uterine endometriosis and any polymorphisms in the AHRR, AHR, ARNT, or CYP1A1 genes analyzed in the present study.

SOMATOSTATIN GENE EXPRESSION IN THE DEVELOPING MONKEY FRONTAL AND CEREBELLAR CORTICES

Somatostatin (SRIF) mRNA was determined in the developing monkey frontal and cerebellar cortices by the dot blot and the northern blot analyses at embryonic day 120 (E120), embryonic day 140 (E140), newborn stage (Nb), postnatal day 60 (P60) and adult stage (Ad.) At E120, at which time the migration of the cortical neurons had already been completed, SRIF mRNA was detectable with 50% of the maximal value at E140 in the cerebral frontal cortex (von Bonin and Baileys area FD). After E140, the level of mRNA gradually declined to the adult level by P60 with 25% of the maximal value. In the cerebellum, SRIF mRNA was highly expressed at E120. The level decreased to 18% of the maximum at E140. Between the newborn and adult stages, there existed no positive signal of the mRNA. In contrast, both fetal and adult liver tissues contained no amounts of SRIF mRNA. We discussed the physiological meanings of the enhanced SRIF gene expression in the developing monkey cerebral and cerebellar cortices.

Expression of the gene for nerve growth factor (NGF) in the monkey central nervous system

The expression of the gene for nerve growth factor (NGF) was examined in the central nervous system of adult and fetal monkeys. In adults, the highest level of NGF mRNA was found in the hippocampus and relatively high levels were observed in the cerebral cortices and thalamus. NGF mRNA was also detected in the cerebellum and the caudate nucleus. In the spinal cord, there was no evidence of the mRNA. The levels of NGF mRNA were closely correlated with those of NGF. At embryonic day 140 (E140), levels of NGF mRNA in the visual cortex and cerebellum were three times higher than those at the adult stage. Our previous study on the ontogeny of NGF (Hayashi, M. et al., Neuroscience, 36 (1990) 683-689) showed that the level of NGF in the visual cortex at E140 is the same as that at adult stage. Thus, at the fetal stage, NGF may be actively transported from the cerebral cortex to other regions of the brain, such as the basal forebrain area. By contrast, the levels of NGF and NGF mRNA in the cerebellum were almost the same at the adult and fetal stages, suggesting that NGF, which is synthesized in the cerebellum, may be taken up locally by cerebellar cells.