ACTH-induced mitochondrial DBI receptor (MDR) and diazepam binding inhibitor (DBI) expression in adrenals of hypophysectomized rats is not cause-effect related to its immediate steroidogenic action.
Diazepam binding inhibitor (DBI) is a 10-kDa polypeptide that is enriched in steroidogenic cells such as adrenocortical, Leydig, and glial cells. In these cells, DBI and some of its processing products bind to the mitochondrial DBI receptor (MDR), located on the outer mitochondrial membrane, and stimulate pregnenolone formation by facilitating cholesterol access to the inner mitochondrial membrane where the cytochrome P-450 side chain cleavage enzyme is located. To determine whether the ACTH-induced increase in adrenal steroidogenesis occurs via changes in DBI and MDR expression the adrenal content of DBI-like immunoreactivity (DBI-LI), the MDR density, and the expression of mRNAs encoding for DBI and MDR were studied in hypophysectomized rats treated with vehicle or ACTH. After 9 days from the hypophysectomy, the levels of DBI-like immunoreactivity (DBI-LI) and DBI-mRNA declined to approximately 20% of their normal value; in contrast MDR-density and MDR-mRNA levels were reduced by 50-60% and were associated to a similar decrease in the activity of type A monoamine oxidase, a marker for mitochondrial proteins. Prolonged administration of ACTH-R (ACTH in saline containing 16% gelatin, 15 U/kg/day, from day 7 after surgery) to hypophysectomized rats, completely restored DBI and MDR adrenal expression to values similar to those of sham-operated rats. Our results indicate that ACTH, probably acting at the transcriptional level, is required for the normal expression of DBI and MDR in adrenal cortex. Changes in DBI and MDR expression after ACTH administration were not temporally related to the immediate steroidogenesis induced by ACTH, and may reflect its long-term trophic action on adrenocortical cells.
Cavallaro
S
S
Fidia-Georgetown Institute for the Neurosciences, Georgetown University School of Medicine, Washington, DC 20007.
Pani
L
L
Guidotti
A
A
Costa
E
E
D000311:Adrenal Glands / Q000201:enzymology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D026261:Diazepam Binding Inhibitor; D005786:Gene Expression Regulation / Q000502:physiology; D007016:Hypophysectomy; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear
D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; C078199:diazepam-binding inhibitor receptor; D000324:Adrenocorticotropic Hormone; D008995:Monoamine Oxidase