Testosterone prevents castration-induced reduction in peripheral benzodiazepine receptors in Cowper's gland and adrenal

doi:10.1016/0006-8993(92)90452-F

Brain Research

Volume 572, Issues 1–2, 14 February 1992, Pages 72-75

https://doi.org/10.1016/0006-8993(92)90452-F Get rights and content

Abstract

The effect of surgical castration of adult male Sprague-Dawley rats on peripheral and central benzodiazepine (BZ) receptors was studied. Following removal of the testes, a significant decrease in the density of peripheral BZ receptors (PBR) was observed in Cowper's glands (71%; P < 0.005) and the adrenal (31%; P < 0.01), but not in the heart. Administration of testosterone acetate (TA) prevented castration-induced PBR depletion. Orchiectomy per se, as well as TA administration to castrated rats, had no effects on central or peripheral BZ receptors in whole brain without the cerebellum. These results indicate the regulatory role of testosterone in the regulation of PBR in Cowper's glands and adrenal.

References (28)

AmiriZ. et al.
Testosterone and cyproterone acetate modulate peripheral but not central benzodiazepine receptors in rats
Brain Research
(1991)
AnholtR.R.H. et al.
Depletion of peripheral-type benzodiazepine receptors after hypophysectomy in rat adrenal gland and testis
Eur. J. Pharmacol.
(1985)
AnholtR.R.H. et al.
The peripheral-type benzodiazepine receptor: localization to the mitochondrial membrane
J. Biol. Chem.
(1986)
BasileA.S. et al.
Adrenalectomy reduces the density of ‘peripheral-type’ binding sites for benzodiazepines in rat kidney
Eur. J. Pharmacol.
(1985)
GavishM. et al.
Modulation of peripheral benzodiazepine binding sites following chronic estradiol treatment
Eur. J. Pharmacol.
(1986)
GavishM. et al.
Regulation of central and peripheral benzodiazepine receptors in progesterone-treated rats
Brain Research
(1987)
KatzY. et al.
Identification and distribution of peripheral benzodiazepine binding sites in male rat genital tract
Biochem. Pharmacol.
(1990)
Le FurG. et al.
Peripheral benzodiazepine binding sites: effect of PK 11195, 1if1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline car☐amide. I. In vitro studies
Life Sci.
(1983)
LowryO.H. et al.
Protein measurement with the Folin phenol reagent
J. Biol. Chem.
(1951)
PapadopoulosV. et al.
The peripheral-type benzodiazepine receptor is functionally linked to Leydig cell steroidogenesis
J. Biol. Chem.
(1990)

PoyetP. et al.

Comparison of the antiandrogenic/androgenic activities of flutamide, cyproterone acetate, and megestrol acetate

Mol. Cell. Endocrinol.

(1985)

RittaM.N. et al.

Effect of GABA and benzodiazepines on testicular androgen production

Life Sci.

(1987)

TaniguchiT. et al.

[³H]Diazepam binding sites on rat heart and kidney

Biochem. Pharmacol.

(1982)

Van De PollN.E. et al.

Effects of testosterone, estrogen, and dihydrotestosterone upon aggressive and sexual behavior of female rats

Horm. Behav.

(1986)

Cited by (18)

Regulation of Mitochondrial, Cellular, and Organismal Functions by TSPO
2018, Advances in Pharmacology
Citation Excerpt :
This TSPO expression suggests that TSPO might play a role in spermatogonial mitosis (Manku et al., 2012). We found that testosterone levels serve to maintain TSPO levels in Cowper's gland of the male reproductive tract (Weizman, Amiri, Katz, Snyder, & Gavish, 1992). In female rats, TSPO expression increases in the ovaries and uterus of pregnant rats (Weizman, Dagan, Snyder, & Gavish, 1997).
In 1999, the enigma of the 18 kDa mitochondrial translocator protein (TSPO), also known as the peripheral-type benzodiazepine receptor, was the seeming disparity of the many functions attributed to TSPO, ranging from the potential of TSPO acting as a housekeeping gene at molecular biological levels to adaptations to stress, and even involvement in higher emotional and cognitive functioning, such as anxiety and depression. In the years since then, knowledge regarding the many functions modulated by TSPO has expanded, and understanding has deepened. In addition, new functions could be firmly associated with TSPO, such as regulation of programmed cell death and modulation of gene expression. Interestingly, control by the mitochondrial TSPO over both of these life and death functions appears to include Ca⁺⁺ homeostasis, generation of reactive oxygen species (ROS), and ATP production. Other mitochondrial functions under TSPO control are considered to be steroidogenesis and tetrapyrrole metabolism. As TSPO effects on gene expression and on programmed cell death can be related to the wide range of functions that can be associated with TSPO, several of these five elements of Ca⁺⁺, ROS, ATP, steroids, and tetrapyrroles may indeed form the basis of TSPO's capability to operate as a multifunctional housekeeping gene to maintain homeostasis of the cell and of the whole multicellular organism.
Chronic high fat, high cholesterol supplementation decreases 18 kDa Translocator Protein binding capacity in association with increased oxidative stress in rat liver and aorta
2010, Food and Chemical Toxicology
It is well known that high fat and high cholesterol levels present a contributing factor to pathologies including fatty liver and atherosclerosis. Oxidative stress is also considered to play a role in these pathologies. The 18 kDa Translocator Protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor, is known to be involved in cholesterol metabolism, oxidative stress, and cardiovascular pathology. We applied a high fat high cholesterol atherogenic (HFHC) diet to rats to study correlations between cardiovascular and liver pathology, oxidative stress, and TSPO expression in the liver and the cardiovascular system. This study corroborates the presence of increased oxidative stress markers and decreased anti-oxidants in liver and aorta. In addition, it appeared that induction of oxidative stress in the liver and aorta by atherogenic HFHC diet was accompanied by a reduction in TSPO binding density in both these tissues. Our data suggest that involvement of TSPO in oxidative stress and ROS generation, as reported in other studies, may also take part in atherogenesis as induced by HFHC diet. Presently, it is not clear whether this TSPO response is compensatory for the stress induced by HFHC diet or is a participant in the induction of oxidative stress.
Estradiol modulates uterine 18 kDa translocator protein gene expression in uterus and kidney of rats
2009, Molecular and Cellular Endocrinology
We examined the effect of ovariectomy, with and without estradiol treatment, on 18 kDa translocator protein (TSPO) gene expression and its binding density in the uterus and kidney of rats. Ovariectomy causes a significant decrease in uterine, but not renal TSPO binding density, while estradiol treatment of ovariectomized rats restored TSPO binding density in the uterus. These TSPO density levels did not correlate with steady state or new RNA transcription. Our in vivo study suggests that estradiol is responsible for the maintenance of uterine TSPO density via transcriptional mechanisms. Our in vivo study also suggests that in the kidney estradiol appears to operate via post-transcriptional mechanisms to maintain TSPO density.
The peripheral-type benzodiazepine receptor and the cardiovascular system. Implications for drug development
2006, Pharmacology and Therapeutics
Peripheral-type benzodiazepine receptors (PBRs) are abundant in the cardiovascular system. In the cardiovascular lumen, PBRs are present in platelets, erythrocytes, lymphocytes, and mononuclear cells. In the walls of the cardiovascular system, PBR can be found in the endothelium, the striated cardiac muscle, the vascular smooth muscles, and the mast cells. The subcellular location of PBR is primarily in mitochondria. The PBR complex includes the isoquinoline binding protein (IBP), voltage-dependent anion channel (VDAC), and adenine nucleotide transporter (ANT). Putative endogenous ligands for PBR include protoporphyrin IX, diazepam binding inhibitor (DBI), triakontatetraneuropeptide (TTN), and phospholipase A2 (PLA2). Classical synthetic ligands for PBR are the isoquinoline 1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinolinecarboxamide (PK 11195) and the benzodiazepine 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (Ro5 4864). Novel PBR ligands include N,N-di-n-hexyl 2-(4-fluorophenyl)indole-3-acetamide (FGIN-1-27) and 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (SSR180575), both possessing steroidogenic properties, but while FGIN-1-27 is pro-apoptotic, SSR180575 is anti-apoptotic. Putative PBR functions include regulation of steroidogenesis, apoptosis, cell proliferation, the mitochondrial membrane potential, the mitochondrial respiratory chain, voltage-dependent calcium channels, responses to stress, and microglial activation. PBRs in blood vessel walls appear to take part in responses to trauma such as ischemia. The irreversible PBR antagonist, SSR180575, was found to reduce damage correlated with ischemia. Stress, anxiety disorders, and neurological disorders, as well as their treatment, can affect PBR levels in blood cells. PBRs in blood cells appear to play roles in several aspects of the immune response, such as phagocytosis and the secretion of interleukin-2, interleukin-3, and immunoglobulin A (IgA). Thus, alterations in PBR density in blood cells may have immunological consequences in the affected person. In conclusion, PBR in the cardiovascular system may represent a new target for drug development.
Platelet peripheral-type benzodiazepine in pregnancy and lactation
1999, Neuropsychopharmacology
The aim of the present study was to investigate the impact of hormonal changes during pregnancy and lactation on the expression of peripheral-type benzodiazepine receptors in platelet membranes. Platelet peripheral benzodiazepine receptor binding characteristics, Hamilton anxiety and depression rating Scores, and progesterone and prolactin (PRL) levels were evaluated during pregnancy and lactation in 17 pregnant women [first (n = 9) and third (n = 8) trimesters], 10 lactating women, and 8 nonpregnant women. A significant decrease (38–41%) in peripheral benzodiazepine receptor density was observed in women during the third trimester of pregnancy when compared to nonpregnant controls and women in their first trimester of pregnancy. The decrease is peripheral benzodiazepine receptors was parallel to the peak in progesterone and PRL secretion. The reduction in peripheral benzodiazepine receptor expression is hormone-dependent and may play a regulatory role geared to prevent pregnancy-related overactivity of the hypothalamic–pituitary-ovarian, hypothalamic–pituitary-adrenal, and hypothalamic-PRL axes.
Molecular and functional properties of mitochondrial benzodiazepine receptors
1995, BBA - Reviews on Biomembranes

View all citing articles on Scopus

View full text

Testosterone prevents castration-induced reduction in peripheral benzodiazepine receptors in Cowper's gland and adrenal

Abstract

Brain Research

Eur. J. Pharmacol.

J. Biol. Chem.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Brain Research

Biochem. Pharmacol.

Life Sci.

J. Biol. Chem.

J. Biol. Chem.

Mol. Cell. Endocrinol.

Life Sci.

Biochem. Pharmacol.

Horm. Behav.