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Effects of castration and testosterone administration on angiotensin II receptor mRNA expression and
Ryuto Nakazawa1, Masami Tanaka, Takeshi Takahashi
1Department of Urology, St. Marianna University, Kawasaki, Japan.
Abstract:
We investigated the effects of castration and androgen administration on angiotensin II receptor mRNA expression and apoptosis related proteins in the rat bladders. Sprague-Dawley rats were divided into three groups: the control group (sham operation; n = 8), the castration group (castrated, 8 weeks old, n = 8) and the castration plus testosterone group (1% testosterone gel administrated percutaneously into the dorsum daily for 8 weeks starting at 4 weeks after castration, n = 8). Bladder total RNA was extracted, and real-time PCR was performed to quantitatively measure the mRNA expression of angiotensin converting enzyme (ACE), angiotensin II (A II) receptor type 1 (AT1 receptor) and A II receptor type II (AT2 receptor). Western blotting was performed to determine the expression of apoptosis-related proteins. Expression of AT2 receptor mRNA and caspase-3 protein significantly increased in the rat bladder after castration, and these increases were reduced to control levels by testosterone administration. These results suggest that expression of AT2 receptor and caspase-3 in the bladder is androgen-dependent. Expression of Bcl-2 and Bax protein in the rat bladder was not altered by castration. Expression of mitogen-activated protein (MAP) kinase phosphatase-1 protein in the rat urinary bladder was significantly increased by castration, but this increase was smaller with testosterone administration. These results suggest that expression of AT2 receptor mRNA and apoptosis-related proteins in the rat urinary bladder are affected by the change of androgen environment. The present study was the first to clarify the relationship between AT2 receptor and androgen in the urinary bladder.
Insights
Castration increases angiotensin II receptor type 2 (AT2 receptor) mRNA and caspase-3 in rat bladders, effects reversed by testosterone. Bladder AT2 receptor and apoptosis are androgen-dependent.
Area of Science:
- Urology
- Endocrinology
- Molecular Biology
Background:
- Androgen levels significantly influence various physiological processes.
- The role of androgens in regulating urinary bladder function and molecular pathways remains incompletely understood.
- Angiotensin II receptors and apoptosis-related proteins are implicated in bladder pathophysiology.
Purpose of the Study:
- To investigate the impact of castration and subsequent androgen (testosterone) administration on angiotensin II receptor (AT1 and AT2) mRNA expression in rat bladders.
- To examine the effects of altered androgen levels on the expression of key apoptosis-related proteins (caspase-3, Bcl-2, Bax, MAP kinase phosphatase-1) in the rat urinary bladder.
- To elucidate the relationship between androgen status and AT2 receptor expression and apoptosis in the urinary bladder.
Main Methods:
- Utilized a rat model with three groups: control (sham operation), castration, and castration plus testosterone administration.
- Quantified mRNA expression of angiotensin converting enzyme (ACE), AT1 receptor, and AT2 receptor using real-time PCR.
- Determined the protein expression levels of apoptosis-related factors (caspase-3, Bcl-2, Bax, MAP kinase phosphatase-1) via Western blotting.
Main Results:
- Castration led to a significant increase in AT2 receptor mRNA and caspase-3 protein expression in rat bladders.
- Testosterone administration reversed these increases, returning AT2 receptor and caspase-3 levels to control levels.
- Bcl-2 and Bax protein expression remained unchanged, while MAP kinase phosphatase-1 expression increased post-castration but was reduced with testosterone treatment.
Conclusions:
- Urinary bladder expression of AT2 receptor mRNA and caspase-3 protein is significantly influenced by the androgen environment and is androgen-dependent.
- Changes in androgen levels affect the expression of specific apoptosis-related proteins in the rat urinary bladder.
- This study provides the first evidence clarifying the direct relationship between AT2 receptor and androgen regulation within the urinary bladder.
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