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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Side Effect Management
Testosterone induced hypertension may be mediated by a T metabolite
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<blockquote data-quote="Nelson Vergel" data-source="post: 17218" data-attributes="member: 3"><p><em>HYPERTENSIONAHA.115.05396 </em></p><p><em></em></p><p><em></em><strong>6&#946;-Hydroxytestosterone, A Cytochrome P450 1B1 Metabolite of Testosterone, Contributes to Angiotensin II&#8211;Induced Hypertension and Its Pathogenesis in Male Mice</strong></p><p></p><p><strong>Abstract</strong></p><p></p><p>Previously, we showed that <em>Cyp1b1</em> gene disruption minimizes angiotensin II&#8211;induced hypertension and associated pathophysiological changes in male mice. This study was conducted to test the hypothesis that cytochrome P450 1B1-generated metabolites of testosterone, 6&#946;-hydroxytestosterone and 16&#945;-hydroxytestosterone, contribute to angiotensin II&#8211;induced hypertension and its pathogenesis. Angiotensin II infusion for 2 weeks increased cardiac cytochrome P450 1B1 activity and plasma levels of 6&#946;-hydroxytestosterone, but not 16&#945;-hydroxytestosterone, in<em>Cyp1b1</em>[SUP]<em>+/+</em>[/SUP] mice without altering <em>Cyp1b1</em> gene expression; these effects of angiotensin II were not observed in <em>Cyp1b1</em>[SUP]&#8722;/&#8722;[/SUP] mice. Angiotensin II&#8211;induced increase in systolic blood pressure and associated cardiac hypertrophy, and fibrosis, measured by intracardiac accumulation of &#945;-smooth muscle actin, collagen, and transforming growth factor-&#946;, and increased nicotinamide adenine dinucleotide phosphate oxidase activity and production of reactive oxygen species; these changes were minimized in <em>Cyp1b1</em>[SUP]&#8722;/&#8722;[/SUP] or castrated <em>Cyp1b1</em>[SUP]<em>+/+</em>[/SUP] mice, and restored by treatment with 6&#946;-hydroxytestoterone. In <em>Cyp1b1</em>[SUP]<em>+/+</em>[/SUP] mice, 6&#946;-hydroxytestosterone did not alter the angiotensin II&#8211;induced increase in systolic blood pressure; the basal systolic blood pressure was also not affected by this agent in either genotype. Angiotensin II or castration did not alter cardiac, angiotensin II type 1 receptor, angiotensin-converting enzyme, Mas receptor, or androgen receptor mRNA levels in <em>Cyp1b1</em>[SUP]<em>+/+</em>[/SUP] or in <em>Cyp1b1</em>[SUP]&#8722;/&#8722;[/SUP] mice. These data suggest that the testosterone metabolite, 6&#946;-hydroxytestosterone, contributes to angiotensin II&#8211;induced hypertension and associated cardiac pathogenesis in male mice, most probably by acting as a permissive factor. Moreover, cytochrome P450 1B1 could serve as a novel target for developing agents for treating renin&#8211;angiotensin and testosterone-dependent hypertension and associated pathogenesis in males.</p></blockquote><p></p>
[QUOTE="Nelson Vergel, post: 17218, member: 3"] [I]HYPERTENSIONAHA.115.05396 [/I][B]6β-Hydroxytestosterone, A Cytochrome P450 1B1 Metabolite of Testosterone, Contributes to Angiotensin II–Induced Hypertension and Its Pathogenesis in Male Mice[/B] [B]Abstract[/B] Previously, we showed that [I]Cyp1b1[/I] gene disruption minimizes angiotensin II–induced hypertension and associated pathophysiological changes in male mice. This study was conducted to test the hypothesis that cytochrome P450 1B1-generated metabolites of testosterone, 6β-hydroxytestosterone and 16α-hydroxytestosterone, contribute to angiotensin II–induced hypertension and its pathogenesis. Angiotensin II infusion for 2 weeks increased cardiac cytochrome P450 1B1 activity and plasma levels of 6β-hydroxytestosterone, but not 16α-hydroxytestosterone, in[I]Cyp1b1[/I][SUP][I]+/+[/I][/SUP] mice without altering [I]Cyp1b1[/I] gene expression; these effects of angiotensin II were not observed in [I]Cyp1b1[/I][SUP]−/−[/SUP] mice. Angiotensin II–induced increase in systolic blood pressure and associated cardiac hypertrophy, and fibrosis, measured by intracardiac accumulation of α-smooth muscle actin, collagen, and transforming growth factor-β, and increased nicotinamide adenine dinucleotide phosphate oxidase activity and production of reactive oxygen species; these changes were minimized in [I]Cyp1b1[/I][SUP]−/−[/SUP] or castrated [I]Cyp1b1[/I][SUP][I]+/+[/I][/SUP] mice, and restored by treatment with 6β-hydroxytestoterone. In [I]Cyp1b1[/I][SUP][I]+/+[/I][/SUP] mice, 6β-hydroxytestosterone did not alter the angiotensin II–induced increase in systolic blood pressure; the basal systolic blood pressure was also not affected by this agent in either genotype. Angiotensin II or castration did not alter cardiac, angiotensin II type 1 receptor, angiotensin-converting enzyme, Mas receptor, or androgen receptor mRNA levels in [I]Cyp1b1[/I][SUP][I]+/+[/I][/SUP] or in [I]Cyp1b1[/I][SUP]−/−[/SUP] mice. These data suggest that the testosterone metabolite, 6β-hydroxytestosterone, contributes to angiotensin II–induced hypertension and associated cardiac pathogenesis in male mice, most probably by acting as a permissive factor. Moreover, cytochrome P450 1B1 could serve as a novel target for developing agents for treating renin–angiotensin and testosterone-dependent hypertension and associated pathogenesis in males. [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Side Effect Management
Testosterone induced hypertension may be mediated by a T metabolite
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