A Circannual Clock Drives Expression of Genes Central for Seasonal Reproduction

Abstract

Animals living in temperate zones anticipate seasonal environmental changes to adapt their biological functions, especially reproduction and metabolism. Two main physiological mechanisms have evolved for this adaptation: intrinsic long-term timing mechanisms with an oscillating period of approximately 1 year, driven by a circannual clock [1], and synchronization of biological rhythms to the sidereal year using day length (photoperiod) [2]. In mammals, the pineal hormone melatonin relays photoperiodic information to the hypothalamus to control seasonal physiology through well-defined mechanisms [3-6]. In contrast, little is known about how the circannual clock drives endogenous changes in seasonal functions. The aim of this study was to determine whether genes involved in photoperiodic time measurement (TSHβ and Dio2) and central control of reproduction (Rfrp and Kiss1) display circannual rhythms in expression under constant conditions. Male European hamsters, deprived of seasonal time cues by pinealectomy and maintenance in constant photoperiod, were selected when expressing a subjective summer or subjective winter state in their circannual cycle of body weight, temperature, and testicular size. TSHβ expression in the pars tuberalis (PT) displayed a robust circannual variation with highest level in the subjective summer state, which was positively correlated with hypothalamic Dio2 and Rfrp expression. The negative sex steroid feedback was found to act specifically on arcuate Kiss1 expression. Our findings reveal TSH as a circannual output of the PT, which in turn regulates hypothalamic neurons controlling reproductive activity. Therefore, both the circannual and the melatonin signals converge on PT TSHβ expression to synchronize seasonal biological activity.

Maternal photoperiod programs hypothalamic thyroid status via the fetal pituitary gland

“…For the former, history-dependent effects at the level of PT TSH production appear to be important (26,27), whereas, for the latter, echoing the present study, large increases in dio2 expression are associated with a slight rise in PT TSH expression (26). Similarly, European hamsters maintained in constant LP show sustained cycles in PT TSH and hypothalamic dio2 expression, correlated with changes in physiological status (28). Collectively, these observations suggest that the internal representation of calendar time (i.e., circannual timekeeping) may emerge through photoperiodic history dependence both in the PT response to photoperiod and in the tanycyte response to the PT.…”

“…(B) The pars tuberalis transduces melatonin signal duration into production of TSH. No history dependence was observed at this level in the present study, but effects have been reported in other seasonal paradigms (27,28) and may contribute to ellipsis in the encoded response to photoperiod. (C) Strong history dependence is seen in the hypothalamic response to TSH, giving a history-dependent internal representation of calendar time.…”

Une horloge circannuelle sonne le réveil des hibernants

“…L'horloge circannuelle régule notamment l'expression de la TSH qui, via l'hormone T3 hypothalamique, transmet l'information circannuelle vers des structures centrales contrôlant de grandes fonctions biologiques, incluant probablement l'hibernation. L'horloge de la pars tuberalis a également été impliquée dans le contrôle circannuel de la [3]. Des hamsters mâles ont été privés de repères saisonniers en les exposant à une photopériode fixe et en supprimant la synthèse de mélatonine par pinéa-lectomie.…”

“…Pour émerger de leur terrier au jour dit, en l'absence de toute information extérieure, les animaux doivent disposer d'un système endogène de mesure du temps qui sonne le signal du réveil interne. Ce système fait intervenir une horloge circannuelle (circa : environ ; annus : an) endogène qui contrôle la synthèse de protéines hépatiques impliquées dans le réveil métabolique [2], et des mécanismes neuroendocriniens qui activent la reproduction [3].…”

“…Cela suggère que le système endogène à l'origine de l'horloge circannuelle est issu de mécanismes ancestraux communs [4,5]. Nous avons ainsi montré que le hamster d'Europe (Cricetus cricetus), maintenu en conditions constantes de photopériode et de température, pré-sente un rythme circannuel de reproduction et de masse corporelle [3,6]. À ce jour, la localisation et les méca-nismes moléculaires de l'horloge circannuelle sont toujours inconnus.…”