Contribution of testosterone to the clock system in rat prostate mesenchyme cells

M. Kawamura, H. Tasaki, I. Misawa, G. Chu, Nobuhiko Yamauchi, M. A. Hattori

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Summary: 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 Bmal1, Clock, Per2 and Nr1d1 under a deficient state of testosterone. In vivo studies showed that the Bmal1 mRNA expression in the prostates displayed a peak at ZT 20 and a trough at ZT 12. Both Bmal1 and Clock transcripts decreased after castration. Conversely, the expression of Per2 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 Per2 oscillation was generated in response to dexamethasone. The circadian rhythms of Bmal1 and Nr1d1 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 Bmal1, Clock and Casp3 in cultured cells, whereas the Per2 and Nr1d1 transcripts were significantly inhibited. Collectively, the present results demonstrated that Bmal1 and Clock, but not Per2 and Nr1d1, 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.

Original languageEnglish
Pages (from-to)225-233
Number of pages9
JournalAndrology
Volume2
Issue number2
DOIs
Publication statusPublished - Mar 1 2014

Fingerprint

Mesoderm
Testosterone
Prostate
Castration
Epithelium
Circadian Rhythm
Androgens
Caspase 3
Dexamethasone
Genes
Cultured Cells
Staining and Labeling
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Reproductive Medicine
  • Endocrinology
  • Urology

Cite this

Contribution of testosterone to the clock system in rat prostate mesenchyme cells. / Kawamura, M.; Tasaki, H.; Misawa, I.; Chu, G.; Yamauchi, Nobuhiko; Hattori, M. A.

In: Andrology, Vol. 2, No. 2, 01.03.2014, p. 225-233.

Research output: Contribution to journalArticle

Kawamura, M. ; Tasaki, H. ; Misawa, I. ; Chu, G. ; Yamauchi, Nobuhiko ; Hattori, M. A. / Contribution of testosterone to the clock system in rat prostate mesenchyme cells. In: Andrology. 2014 ; Vol. 2, No. 2. pp. 225-233.
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