Hormonal and Developmental Regulation of Adrenodoxin Messenger Ribonucleic Acid in Steroidogenic Tissues*

Abstract

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.

cAMP post-transcriptionally diminishes the abundance of adrenodoxin reductase mRNA.

“…Nuclear lamin mRNA in the same cells showed a slight 2-fold increase, consistent with the known mild inductive effect of cAMP on lamin mRNA. Similarly, the abundance of adrenodoxin mRNA in'these same cells increased t4-fold with 12 h of stimulation (data not shown), consistent with our observations in JEG-3 cells (13) and in primary cultures of human ovarian granulosa, adrenal, and testicular cells (18). Thus the cAMP-induced reduction in AR mRNA is specific to that mRNA and does not reflect a global effect on the cells.…”

“…and cell types (1,28), reaching maximal accumulation after 36-48 h (9,13,18,29). Yet AR mRNA was induced minimally in human granulosa cells when P450scc and adrenodoxin mRNAs were maximal (19).…”

“…Three species of human adrenodoxin mRNAs that differ only in the lengths of their 3' untranslated regions (13) are encoded by two genes (14,15) on chromosome 11q22 (8,16) that are expressed in all tissues examined (13). Adrenodoxin mRNA also accumulates in response to tropic hormones acting by way of cAMP (13,17,18), apparently through a posttranscriptional mechanism (S.T.B. and W.L.M., unpublished data).…”

The Transcriptional Regulating Protein of 132 kDa (TReP-132) Enhances P450scc Gene Transcription through Interaction with Steroidogenic Factor-1 in Human Adrenal Cells

“…The enzyme P450scc is encoded by a single human gene, CYP11A1 (2), on chromosome 15q23-24 (3), and its expression is regulated hormonally at the transcriptional level (4). Although expression of the gene has been detected in the central nervous system (5), P450scc transcript and protein are expressed for the most part in steroidogenic tissues such as adrenals, ovaries (6), testis, and the placenta (7)(8)(9). The hormonal regulation and developmental pattern of expression of P450scc are species-and tissue-specific (10).…”

Human adrenodoxin reductase: two mRNAs encoded by a single gene on chromosome 17cen----q25 are expressed in steroidogenic tissues.

“…Adrenodoxin is encoded by a single functional gene on chromosome llql3-+qter (15) that encodes several mRNAs differing in the lengths of their 3' untranslated regions (16). This mRNA also accumulates in steroidogenic tissues stimulated with cAMP or tropic hormones (17). However, unlike P450scc mRNA, the half-life of adrenodoxin mRNA appears to be regulated posttranscriptionally (16,18).…”