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Published on: January 12, 2016
Caspase-3 and -6 expression and activation are targeted by hormone action in the rat ventral prostate during the
Asma Omezzine1, Claire Mauduit, Eric Tabone
1Institut National de la Santé et de la Recherche Médicale (INSERM U 407), Faculté de Médecine Lyon-Sud, 69921, Oullins, France.
Abstract:
Although the apoptotic cell death process in the prostate is known to be under the control of androgens, the key components targeted by the hormones remain to be investigated. In the present study, we report that the expression and the activation of the effector caspases-3 and -6 are under the control of testosterone in the adult rat ventral prostate. By using a model of adult castrated rats supplemented (or not) with androgens, we observed an increase in caspase-3 (3-fold) and -6 (4-fold) mRNA (P < 0.0001) and procaspase-3 (32 kDa) and -6 (34 kDa) protein levels by 3 days and 1 wk, respectively, after castration in the ventral prostate. Castration also induced an increase in the activation of the procaspases in the ventral prostate, since active (cleaved) caspase-3 (17 kDa) and -6 (12 kDa) forms reached maximal levels by 1 wk after castration. Testosterone administration to castrated adult rats prevented the increase in caspase-3 and -6 mRNA as well as in procaspase-3 and -6 and active caspase-3 and -6 levels in the ventral prostate lobe. In contrast, no changes were observed in the initiator caspase-8 mRNA and protein (procaspase and active) levels after castration. No changes in caspase-3 and -6 expression and activation were observed in the dorsolateral and anterior prostate lobes after castration and testosterone supplementation. Together, the present results show that testosterone inhibits apoptosis in the ventral prostate by potentially targeting the transcriptional activity of effector caspase-3 and -6 genes (but not of casapase-8 gene) as well as the cleavage of procaspase-3 and -6 into active enzymes.
Insights
Testosterone regulates apoptosis in the adult rat ventral prostate by controlling effector caspases-3 and -6 expression and activation. This hormonal regulation specifically targets the ventral prostate, not other lobes.
Area of Science:
- Molecular Biology
- Endocrinology
- Cell Biology
Background:
- Androgens are known to control apoptotic cell death in the prostate.
- Specific molecular targets of androgens in prostate apoptosis remain largely unelucidated.
Purpose of the Study:
- To investigate the role of testosterone in regulating effector caspases (caspase-3 and -6) in the adult rat ventral prostate.
- To determine if testosterone affects the expression and activation of specific caspases involved in apoptosis.
Main Methods:
- Utilized a castration model in adult rats, with and without testosterone supplementation.
- Quantified mRNA and protein levels of caspases-3, -6, and -8 using molecular biology techniques.
- Assessed active (cleaved) forms of caspases to determine enzyme activation.
Main Results:
- Castration significantly increased mRNA and procaspase levels of caspase-3 (3-fold) and caspase-6 (4-fold) in the ventral prostate.
- Active caspase-3 and -6 levels were elevated post-castration, indicating increased apoptosis.
- Testosterone administration reversed these castration-induced changes, preventing caspase upregulation and activation.
- No significant changes in caspase-8 (initiator caspase) were observed, and caspase-3/-6 changes were specific to the ventral prostate lobe.
Conclusions:
- Testosterone inhibits apoptosis in the adult rat ventral prostate.
- This inhibition is mediated by suppressing the expression and activation of effector caspases-3 and -6.
- Testosterone's effect appears to target transcriptional activity of caspase-3 and -6 genes and their subsequent cleavage into active forms.
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