In vivo studies on the role of the peripheral benzodiazepine receptor (PBR) in steroidogenesis.
In various steroidogenic cell models, mitochondrial preparations and submitochondrial fractions, the expression of the mitochondrial 18 kDa peripheral-type benzodiazepine receptor (PBR) protein confers the ability to take up and release, upon ligand activation, cholesterol. Thus, cholesterol becomes available to P450scc on the inner mitochondrial membrane. These in vitro studies were validated by in vivo experiments. Treatment of rats with ginkgolide B (GKB), specifically reduced the ligand binding capacity, protein, and mRNA expression of the adrenocortical PBR and circulating glucocorticoid levels. Treatment with GKB also resulted in inhibition of PBR protein synthesis and corticosterone production by isolated adrenocortical cells in response to ACTH. The ontogeny of both PBR binding capacity and protein directly paralleled that of ACTH-inducible steroidogenesis in rat adrenal cells and in rats injected with ACTH. In addition, the previously described suppression of luteal progesterone synthesis in the pregnant rat by continuous in vivo administration of a gonadotropin-releasing hormone agonist may be due to decreased luteal PBR ligand binding and mRNA. These results suggest that (i) PBR is an absolute prerequisite for adrenocortical and luteal steroidogenesis, (ii) regulation of adrenal PBR expression may be used as a tool to control circulating glucocorticoid levels and (iii) the stress hypo-responsive period of neonatal rats may result from decreased adrenal cortical PBR expression.
Papadopoulos
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V
Department of Cell Biology, Georgetown University Medical Center, Washington, District of Columbia, USA.
Widmaier
E P
EP
Amri
H
H
Zilz
A
A
Li
H
H
Culty
M
M
Castello
R
R
Philip
G H
GH
Sridaran
R
R
Drieu
K
K
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis; D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D020441:Ginkgo biloba / Q000737:chemistry; D005938:Glucocorticoids / Q000096:biosynthesis; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D008183:Luteal Phase; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013256:Steroids / Q000096:biosynthesis*; D000096983:Ginkgo Extract
D000305:Adrenal Cortex Hormones; D005419:Flavonoids; D005938:Glucocorticoids; D007987:Gonadotropin-Releasing Hormone; D010936:Plant Extracts; D011374:Progesterone; D011963:Receptors, GABA-A; D013256:Steroids; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract