Hormonal regulation of peripheral benzodiazepine receptor binding properties is mediated by subunit interaction.
The peripheral benzodiazepine receptor (PBR) is composed of three subunits with molecular masses of 18, 30, and 32 kDa. Many physiological functions have been attributed to the PBR, including regulation of steroidogenesis. Furthermore, the PBR itself is under hormonal regulation. In the current study, we investigated the role of female gonadal sex hormones in the regulation of PBR expression in steroidogenic and nonsteroidogenic tissues. To accomplish this, adult female rats were pharmacologically castrated using chronic administration of the gonadotropin-releasing hormone agonist decapeptyl (triptorelin-D-Trp(6)-LHRH). Half of these rats received 17beta-estradiol as hormone replacement, while a control group received daily injections of vehicle only. We found that PBR binding capacity dropped by 40 and 48% in ovaries and adrenals, respectively, following decapeptyl administration, as opposed to no change in the kidney. This down-regulation of PBR densities was prevented by estradiol replacement. We did not find evidence for transcriptional, posttranscriptional, and translational mechanisms in this decapeptyl-induced down-regulation. In contrast, immunoprecipitation of the PBR complex, using antibodies against the 18- and 32-kDa subunits of the complex, demonstrated that there were changes in PBR subunit interactions, consistent with the down-regulation of PBR binding capacity. These findings represent a novel hormone-dependent posttranslational regulatory mechanism.
Golani
I
I
Department of Pharmacology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 31096 Haifa, Israel.
Weizman
A
A
Leschiner
S
S
Spanier
I
I
Eckstein
N
N
Limor
R
R
Yanai
J
J
Maaser
K
K
Scherübl
H
H
Weisinger
G
G
Gavish
M
M
D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007546:Isoquinolines / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008186:Luteolytic Agents / Q000494:pharmacology; D008970:Molecular Weight; D009928:Organ Specificity; D010053:Ovary / Q000378:metabolism*; D011374:Progesterone / Q000097:blood; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D017329:Triptorelin Pamoate / Q000494:pharmacology*
D007546:Isoquinolines; D008186:Luteolytic Agents; D021122:Protein Subunits; D011963:Receptors, GABA-A; D017329:Triptorelin Pamoate; D011374:Progesterone; D004958:Estradiol; C037850:PK 11195