Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 91, Issue 10, Pages 3850-3856Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2006-0968
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Funding
- NCI NIH HHS [CA 97186] Funding Source: Medline
- NCRR NIH HHS [RR 00163] Funding Source: Medline
- NIA NIH HHS [K23 AG027238, K23 AG027238-03] Funding Source: Medline
- NICHD NIH HHS [U54 HD 42454, U54 HD 12629] Funding Source: Medline
- NIDDK NIH HHS [DK 65083, DK 65204] Funding Source: Medline
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Context: The impact of serum androgen manipulation on prostate tissue hormone levels in normal men is unknown. Studies of men with prostate cancer have suggested that prostatic androgens are preserved in the setting of castration. Tissue androgens might stimulate prostate growth, producing adverse clinical consequences. Objective: The objective of the study was to determine the effect of serum androgen manipulation on intraprostatic androgens in normal men. Design: Thirteen male volunteers ages 35-55 yr (prostate-specific antigen < 2.0 ng/ml; normal transrectal ultrasound) were randomly assigned to: 1) a long-acting GnRH-antagonist, acyline, every 2 wk; 2) acyline plus testosterone ( T) gel ( 10 mg/d); or 3) placebo for 28 d. Serum hormones were assessed weekly. Prostate biopsies were obtained on d 28. Extracted androgens were measured by RIA, and immunohistochemistry for androgen-regulated proteins was performed. Results: The mean decrease in serum T was 94%, whereas prostatic T and dihydrotestosterone levels were 70 and 80% lower, respectively, in subjects receiving acyline alone compared with controls ( P < 0.05). Despite this decrease in prostate androgens, there were no detectable differences in prostate epithelial proliferation, apoptosis, prostate-specific antigen, and androgen receptor expression. Conclusion: In this small study of healthy subjects, despite a 94% decrease in serum T with medical castration, intraprostatic T and dihydrotestosterone levels remained 20-30% of control values, and prostate cell proliferation, apoptosis, and androgen-regulated protein expression were unaffected. Our data highlight the importance of assessing tissue hormone levels. The source of persistent prostate androgens associated with medical castration and their potential role in supporting prostate metabolism deserves further study.
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