Objectives:Recently, adrenal androgens have been targeted as key hormones for the development of castration-resistant prostate cancer therapeutics.
While circulating adrenal androgens originate mainly from the adrenal glands, the testes also supply about 10%. Although widely used in androgen deprivation medical castration therapy, the effect of luteinizing-hormone (LH)-releasing hormone (RH) agonist on adrenal androgens has not been fully studied. In this study, changes in testicular and adrenal androgen levels were measured and compared to adrenocorticotropic hormone (ACTH) levels. To assess the possible role of LH in the adrenal glands, immunohistochemical studies of the LH receptor in normal adrenal glands were performed.
Findings: Forty-seven patients with localized or locally progressive prostate cancer were treated with LH-RH agonist with radiotherapy. Six months after initiation of treatment, testosterone, dihydrotestosterone and estradiol levels were decreased by 90-95%, and dehydroepiandrosterone-sulfate (DHEA-S), DHEA, and androstendione levels were significantly decreased by 26-40%. The suppressive effect of LH-RH agonist at 12 months was maintained. ACTH levels showed an increasing trend at 6 months and a significant increase at 12 months. LH receptors were positively stained in the cortex cells of the reticular layer of the adrenal glands.
Conclusions: The long-term LH-RH agonist treatment reduced adrenal-originated adrenal androgens. LH receptors in the adrenal cortex cells of the reticular layer might account for the underlying mechanism of reduced adrenal androgens.
Written by:
Nishii M, Nomura M, Sekine Y, Koike H, Matsui H, Shibata Y, Ito K, Oyama T, Suzuki K. Are you the author?
Reference: J Androl. 2012 Apr 5. Epub ahead of print.
doi: 10.2164/jandrol.112.016493
PubMed Abstract
PMID: 22492843
UroToday.com Prostate Cancer Section