Profiling the steroidogenic pathway in human fetal and adult adrenals. Journal of society for gynaecologic investigation

OBJECTIVE: Gene expression clearly underlies the marked structural andfunctional differences between the humanfetal adrenal (HFA) and adult adrenal. We thus measured expression of steroidogenic enzymes and associated cofactors in these tissues. METHODS: Real-time reverse transcriptase polymerase chain reaction was used to quantify transcripts encoding steroidogenic enzymes and the cofactors steroidogenic acute regulatory protein (StAR), cytochrome b5 (CYb5), and P450 oxidoreductase (POR). RESULTS: Cholesterol side-chain cleavage mRNA levels were 1.9-fold higher in the HFA than in the adult adrenal. Compared with a nonsignificant difference in 1 7ot-hydroxylase/1 7,20 lyase mRNA abundance, CYb5 and POR were expressed 2.3-fold and 2.0-fold higher, respectively, in the HFA. Dehydroepiandrosterone (DHEA) sulfotransferase transcript (SULT2A 1) was present at 13-fold higher levels in the HFA than the adult. 33-Hydroxysteroid dehydrogenase type II (HSD3B2) mRNA was 127-fold higher in the adult adrenal. StAR, 21-hydroxylase, 1 113 hydroxylase, and aldosterone synthase mRNA abundance did not differ significantly. CONCLUSION: In the HFA, increased mRNAfor cholesterol side-chain cleavage reflects high cholesterol utilization for steroidogenesis. Both CYb5 and POR cofactors may up-regulate 17ot-hydroxylasel17,20 lyase activity and thus DHEA sulfate production in the HFA. High levels ofSULT2A 1 mRNA reflect high DHEA suffonation in the HFA and restricted expression in the adult. Lack ofHSD3B2 in the HFA facilitates DHEA synthesis. The novel finding of high levels of 21-hydroxylase and 113 hydroxylase transcripts in the midgestational HFA meritsfurther investigation. Thus different patterns of steroidogenic enzyme and cofactor gene expression might accountfor some of the phenotypic differences between thefeta