Thyroid hormone and seasonal rhythmicity

Abstract

Living organisms show seasonality in a wide array of functions such as reproduction, fattening, hibernation, and migration. At temperate latitudes, changes in photoperiod maintain the alignment of annual rhythms with predictable changes in the environment. The appropriate physiological response to changing photoperiod in mammals requires retinal detection of light and pineal secretion of melatonin, but extraretinal detection of light occurs in birds. A common mechanism across all vertebrates is that these photoperiod-regulated systems alter hypothalamic thyroid hormone (TH) conversion. Here, we review the evidence that a circadian clock within the pars tuberalis of the adenohypophysis links photoperiod decoding to local changes of TH signaling within the medio-basal hypothalamus (MBH) through a conserved thyrotropin/deiodinase axis. We also focus on recent findings which indicate that, beyond the photoperiodic control of its conversion, TH might also be involved in longer-term timing processes of seasonal programs. Finally, we examine the potential implication of kisspeptin and RFRP3, two RF-amide peptides expressed within the MBH, in seasonal rhythmicity.

Keywords: GnRH neurons; RF-amide; kisspeptins; melatonin rhythm; pars tuberalis; reproduction; seasonality.

Figure 1

T3 implants prevent SP-induced inactivation of the gonadal axis (red line) and reactivate the gonadal axis in SP-adapted Siberian hamsters [green line; after data from Barrett et al. (54) and Murphy et al. (55)]. Siberian hamsters (black line) kept in LP remain indefinitely sexually active (broken lines) unless they are transferred to SP; gonads then progressively regress (testes depicted here, but data are similar for female reproductive organs). However, prolonged SP exposure leads to a spontaneous recrudescence of the gonads, which reflects SP-refractoriness.

Figure 2

Pathways for photoperiodic entrainment in mammals and birds (see text).

Figure 3

The circadian clock of the pars tuberalis links melatonin to the photoperiodic response [after data from Dardente et al. (138) and unpublished data]. (A) Images representative of minimal and maximal mRNA levels in situ hybridization autoradiograms for Cry1, Tef, Six1, Eya3, Tshβ, and Dio2 in sheep kept under SP 8:16 and sheep transferred to LP 16:8 for 3 days (LP3) or 15 days (LP15). (B) The internal coincidence model for photoperiodic time-measurement within the PT; SP situation on the left side, LP on the right side, yellow and black indicate day and night. The transcription of Eya3 is both clock-controlled and inhibited by melatonin, hence the phase-relationship relative to Cry1 expression (a melatonin-induced circadian gene) is similar irrespective of the photoperiod but Eya3 transcription increases only under LP as melatonin inhibition is relieved. (C) Schematics of the transcriptional control of the Tshβ gene by TEF/SIX1/EYA3. Note that EYA3 levels are higher under LP than SP.

Figure 4

A model for long-day refractoriness [adapted from Figure 2 in Ref. (152)]. In sheep (left panel) and hamsters (right panel), exposure to long days (black line) leads to the development of a mechanism of unknown nature, most likely T3-dependent (red line). In sheep, the long-day drive eventually exceeds a “threshold” (blue dotted line); the animal then becomes refractory to long days and spontaneously reverts to an SP phenotype. In hamsters, the long-day drive never exceeds the threshold and the animal displays the LP phenotype indefinitely; exposure to SP is mandatory to get the SP physiological state.

Figure 5

Beyond the long-day response: TH metabolism within the MBH in long-term timing. (A) Representative images of in situ hybridization autoradiograms for Tshβ, Dio2, and Dio3 in sheep under four different endocrine states: LP animals in a spring/summer-like state of reproductive arrest, LP refractory (LPR) animals showing spontaneous reproductive reactivation (late summer/autumn state), SP animals showing autumn/winter-like reproductive activation, and SP refractory (SPR) animals showing spontaneous reproductive arrest [adapted from Saenz de Miera et al. (157)]. (B) Schematics depicting (i) the direct effect of LP and SP on DIO2/DIO3 levels, respectively, intertwined with (ii) the possibility that their activity and the resulting TH metabolism constitutes the core of a long-term timing mechanism involved in refractoriness.