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.

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.

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.