Hormonal and developmental regulation of adrenodoxin messenger ribonucleic acid in steroidogenic tissues

Adrenodoxin is an iron-sulfur protein found in the mitochondria of steroidogenic tissues. It participates in steroidogenesis as an electron transport intermediate for mitochondrial cytochromes P450, including P450scc, the cholesterol side-chain cleavage enzyme. Using a human adrenodoxin cDNA probe recently cloned in our laboratory, we examined the distribution and hormonal regulation of adrenodoxin mRNA in a variety of steroidogenic tissues. Adrenodoxin mRNA was found in all steroidogenic tissues examined. In human fetal testes, adrenodoxin mRNA was more abundant in early gestation, diminishing toward midterm in a pattern closely similar to that we reported previously for P450scc. Unlike P450scc, however, significant amounts of adrenodoxin mRNA were detected in human fetal ovaries, with no discernible gestation-dependent change. The abundance of adrenodoxin mRNA was increased in cultured human granulosa cells by treatment with hCG, FSH, cAMP, and cholera toxin. In human fetal adrenal cells, ACTH and cAMP stimulated accumulation of adrenodoxin mRNA, while in cultured human fetal testicular cells and cultured fetal rhesus monkey ovarian cells, both hCG and cAMP stimulated accumulation of adrenodoxin mRNA. In all of these systems, the accumulation of adrenodoxin mRNA closely paralleled the response of P450scc. These data suggest that the genes for these functionally related but structurally unrelated proteins are regulated in a coordinate manner.