Contribution of testosterone to the clock system in rat prostate mesenchyme cells. (10th December 2013)

• Record Type: Journal Article
• Authors: Kawamura, M.; Tasaki, H.; Misawa, I.; Chu, G.; Yamauchi, N.; Hattori, M‐A.
• Is Part Of: Andrology. Volume 2:Number 2(2014)
• Page Start: 225
• Page End: 233
• Publication Date: 2013-12-10
• Subjects: Andrology -- Periodicals; 616.65
• DOI: 10.1111/j.2047-2927.2013.00161.x
• Languages: English
• ISSNs: 2047-2919

Abstract

<abstract abstract-type="main" id="andr161-abs-0001"> <title>Summary</title> <p>Circadian rhythms are modulated in a variety of peripheral tissues including the prostate, in which the mesenchyme and epithelium cells are controlled under androgens. Here, we investigated the testosterone regulation of core clock genes such as <italic>Bmal1</italic>, <italic> Clock</italic>, <italic> Per2</italic> and <italic>Nr1d1</italic> under a deficient state of testosterone. In vivo studies showed that the <italic>Bmal1</italic> mRNA expression in the prostates displayed a peak at ZT 20 and a trough at ZT 12. Both <italic>Bmal1</italic> and <italic>Clock</italic> transcripts decreased after castration. Conversely, the expression of <italic>Per2</italic> that is promoted by binding of Bmal1 and Clock heterodimers to the E‐box, enhanced or did not decease at least within 1 week after castration. The clock gene transcripts were recovered to the intact levels, when 1 mg testosterone was administered daily for 5 days. Fluorescent immunohistochemical studies revealed the increased staining of caspase 3 in the epithelium and Per2 in both the mesenchyme and epithelium after 1‐week castration. In the mesenchyme cells prepared from castrated rats, the <italic>Per2</italic> oscillation was generated in response to dexamethasone. The circadian rhythms of <italic>Bmal1</italic> and <italic>Nr1d1</italic> transcripts were obviously antiphase in the cells. However, the mesenchyme cells displayed the different profiles in the presence or absence of testosterone; the amplitude of the first phase was significantly decreased by testosterone. Addition of testosterone significantly increased the transcripts of <italic>Bmal1</italic>, <italic> Clock</italic> and <italic>Casp3</italic> in cultured cells, whereas the <italic>Per2</italic> and <italic>Nr1d1</italic> transcripts were significantly inhibited. Collectively, the present results demonstrated that <italic>Bmal1</italic> and <italic>Clock</italic>, but not <italic>Per2</italic> and <italic>Nr1d1</italic>, are down‐regulated in mesenchyme cells by testosterone deficiency. In addition to the conservative interlocked transcriptional–translational feedback loop, it is strongly suggested that the prostate clock system is controlled under androgen.</p> </abstract>