Light and Hormones in Seasonal Regulation of Reproduction and Mood

Abstract

Organisms that inhabit the temperate zone exhibit various seasonal adaptive behaviors, including reproduction, hibernation, molting, and migration. Day length, known as photoperiod, is the most noise-free and widely used environmental cue that enables animals to anticipate the oncoming seasons and adapt their physiologies accordingly. Although less clear, some human traits also exhibit seasonality, such as birthrate, mood, cognitive brain responses, and various diseases. However, the molecular basis for human seasonality is poorly understood. Herein, we first review the underlying mechanisms of seasonal adaptive strategies of animals, including seasonal reproduction and stress responses during the breeding season. We then briefly summarize our recent discovery of signaling pathways involved in the winter depression-like phenotype in medaka fish. We believe that exploring the regulation of seasonal traits in animal models will provide insight into human seasonality and aid in the understanding of human diseases such as seasonal affective disorder (SAD).

Keywords: photoperiod; seasonal adaptation; seasonal affective disorder (SAD); seasonal reproduction; stress response.

Figure 1.

Pars tuberalis–derived TSH (PT-TSH) is the springtime hormone that regulates seasonal reproduction in mammals. Light information sensed by the retina in the eye is transmitted to the pineal gland via the suprachiasmatic nucleus (SCN), where the circadian pacemaker is located (7, 37). The pineal melatonin secretion profile with a clear day-night variation reflects photoperiodic information and regulates the production of PT-TSH (37). Long day–induced PT-TSH acts on ependymal cells in the hypothalamus to drive expression of deiodinase 2 (DIO2) (37). DIO2 encodes the TH-activating enzyme that converts the prohormone T₄ to bioactive T_3, thereby transmitting the springtime signal. To avoid functional crosstalk with pars distalis–derived TSH (PD-TSH), which influences metabolism by regulating the hypothalamic–pituitary–thyroid (HPT) axis (42), PT-TSH exhibits a distinct posttranslational glycosylation (41). PD-TSH is modified with sulfated biantennary N-glycans and rapidly metabolized in the liver. However, PT-TSH has tissue-specific N-glycans and forms a macro-TSH complex with immunoglobulin G (IgG) and albumin in the circulation, resulting in the loss of bioactivity and preventing seasonal thyroid gland overactivity (41). From Nakayama and Yoshimura (2018) (83).

Figure 2.

Involvement of multiple signaling pathways in the emergence of winter depression–like behaviors. The inactivation of multiple signaling pathways under winter conditions were identified by transcriptomic and metabolomic analyses. A chemical genomics approach revealed that seasonal changes in the NRF2-mediated antioxidant pathways regulate winter depression–like behavior (67).