Diazepam-binding inhibitor/acyl-CoA-binding protein mRNA and peripheral benzodiazepine receptor mRNA in endocrine and immune tissues after prenatal diazepam exposure of male and female rats

Peripheral benzodiazepine (BDZ) receptor (PBR) and diazepam-binding inhibit or/acyl-CoA-binding protein (DBI/ACBP) characterized as a ligand at central BDZ receptors, at PER with involvement in the regulation of steroidogenesi s, and as an intracellular acyl-CoA transporter, are both known to interact with BDZ in adult systems. We investigated their expression after prenatal exposure to BDZ. Diazepam (1.25 mg/kg per day s.c.) was administered to ti me-pregnant Long Evans rats from gestational day (GD) 14 to 20. Expression of mRNAs encoding for PER and for DBI/ACBP was studied in the same animals with P-33-labeled 60 mer oligonucleotides (oligos) by in situ hybridization at GD20, and with P-32-labeled oligos by Northern blot in steroidogenic an d immune organs at postnatal day (PN) 14 and in adult offspring. Prenatal d iazepam increased DBI/ACBP mRNA expression in male fetal adrenal and in fet al and PN14 testis. Thymus exhibited increased DBI/ACBP mRNA in male fetuse s and in adult female offspring, and reduced organ weight at PN14 in both s exes. In female spleen, an increase in DBI/ACBP mRNA and a decrease in PER mRNA was seen at PN14. Apart from the finding in spleen, no drug-induced ch anges in PER mRNA were observed. The effects of prenatal diazepam were supe rimposed on treatment-independent sex differences in DBI/ACBP mRNA and PER mRNA expression. Our data indicate that expression of DBI/ACBP mRNA in ster oidogenic and immune organs can be affected by exposure to BDZ during ontog eny, while PER mRNA expression appears to be less sensitive. They further r eveal marked sex differences in the developmental patterns of the two prote ins during pre- and postpubertal ontogeny.