Propylthiouracil causes phase delays and circadian period lengthening in male and female hamsters

Abstract

The thyroid neuroendocrine axis has been implicated in the control of circadian rhythmicity. The present work examined the ability of a thyroid hormone-inhibiting agent, propylthiouracil (PTU), to modulate phase and period of the hamster wheel-running circadian rhythm. The circadian period (tau) of blind male hamsters was lengthened by approximately 0.2 h when they were fed a diet containing 0.6% PTU. Removal of the PTU reversed the change in tau. Pinealectomy did not alter the tau response to PTU. Blind ovariectomized female hamsters showed changes in tau during and after PTU treatment that were similar to those of males. Males were also tested with 0.3, 0.6, or 1.2% PTU diets, and a dose-response relationship was established. Under 14:10 light-dark (LD 14:10) conditions, the phase of activity onset relative to lights off (psi) was not affected by 0.6% PTU. In LD 6:18, mean psi was 16.7 h, but this shortened to 13.3 h during PTU, returning to 16.0 h after PTU removal. In intact males under LD 14:10, the three PTU diet concentrations failed to differentially suppress thyroxine and triiodothyronine levels. Food intake and body weight were differentially reduced by the PTU treatments. A 0.5% quinine hydrochloride diet also reduced food intake and body weight but did not change tau. The inconsistency between the dose-tau response and the dose-thyroid hormone response suggest that PTU may affect circadian rhythmicity independent of its action on the thyroid neuroendocrine axis.