Deiodinases: how non-mammalian research helped shape our present view

Iodothyronine deiodinases are enzymes capable of activating and inactivating thyroid hormones (THs) and have an important role in regulating TH action in tissues throughout the body. Three types of deiodinases (D1, D2 and D3) were originally defined based on their biochemical characteristics. Cloning of the first cDNAs in the 1990s (Dio1 in rat and dio2 and dio3 in frog) allowed to confirm the existence of three distinct enzymes. Over the years, increasing genomic information revealed that deiodinases are present in all chordates, vertebrates and non-vertebrates, and that they can even be found in some mollusks and annelids, pointing to an ancient origin. Research in non-mammalian models has substantially broadened our understanding of deiodinases. In relation to their structure, we discovered for instance that biochemical properties such as inhibition by 6-propyl-2-thiouracil, stimulation by dithiothreitol and temperature optimum are subject to variation. Data from fish, amphibians and birds were key in shifting our view on the relative importance of activating and inactivating deiodination pathways, and in showing the impact of D2 and D3 not only in local but also whole body T3 availability. They also led to the discovery of new local functions such as the acute reciprocal changes in D2 and D3 in hypothalamic tanycytes upon photostimulation, involved in seasonal rhythmicity. With the present possibilities for rapid and precise gene silencing in any species of interest, comparative research will certainly further contribute to a better understanding of the importance of deiodinases for adequate TH action, also in humans.

Seasonal differences in rhythmicity of salivary cortisol in healthy adults

The existence of seasonal changes in secretion of stress hormones and inflammatory mediators by humans is not certain. Here, we aimed to determine whether concentrations of cortisol and IL-6 displayed seasonal rhythmicity. The study was performed in Poznań, Poland (52°N, 16°E) in 7 healthy female volunteers (age 22.6 ± 0.8 yr). Samples of whole mixed unstimulated saliva were collected in winter (February) and summer (June) at 2-h intervals over a 24-h period and analyzed for cortisol and IL-6 by immunoassays. During each season, the subjects answered questionnaires related to their sleeping habits, food intake, physical activity, and perceived seasonality. It turned out that salivary concentrations of cortisol followed a daily rhythm both in winter and summer, as determined by a cosine analysis. However, compared with the winter season, a midline-estimating statistic of rhythm in the summer was significantly higher. Moreover, the rhythm acrophase occurred ~4 h later in the summer than in the winter, whereas the amplitudes did not differ. These fluctuations did not correspond to sleeping habits, food and fluid intake, physical exercise, and the self-assessed chronotype. However, the individuals with higher scores on the seasonal affective disorder scale showed a tendency toward lower relative cortisol amplitude in the summer. In contrast to cortisol, salivary IL-6 concentration did not display daily rhythmicity, and its concentrations did not differ significantly between the seasons. In conclusion, in the summer, cortisol level in saliva is elevated, and its circadian pattern of secretion is shifted. The causes for these alterations do not seem to be related to lifestyle and thus remain to be established.

The Singularity of Cetacea Behavior Parallels the Complete Inactivation of Melatonin Gene Modules

: Melatonin, the hormone of darkness, is a peculiar molecule found in most living organisms. Emerging as a potent broad-spectrum antioxidant, melatonin was repurposed into extra roles such as the modulation of circadian and seasonal rhythmicity, affecting numerous aspects of physiology and behaviour, including sleep entrainment and locomotor activity. Interestingly, the pineal gland—the melatonin synthesising organ in vertebrates—was suggested to be absent or rudimentary in some mammalian lineages, including Cetacea. In Cetacea, pineal regression is paralleled by their unique bio-rhythmicity, as illustrated by the unihemispheric sleeping behaviour and long-term vigilance. Here, we examined the genes responsible for melatonin synthesis (Aanat and Asmt) and signalling (Mtnr1a and Mtnr1b) in 12 toothed and baleen whale genomes. Based on an ample genomic comparison, we deduce that melatonin-related gene modules are eroded in Cetacea.

The singularity of Cetacea behaviour parallels the complete inactivation of melatonin gene modules

Melatonin, the hormone of darkness, is a peculiar molecule found in most living organisms. Emerging as a potent broad-spectrum antioxidant, melatonin was repurposed into extra roles such as the modulation of circadian and seasonal rhythmicity: affecting numerous aspects of physiology and behaviour, including sleep entrainment and locomotor activity. Interestingly, the pineal gland—the melatonin synthesising organ in vertebrates—was suggested to be absent or rudimentary in some mammalian lineages, including Cetacea. In Cetacea, pineal regression is paralleled by their unique bio-rhythmicity, as illustrated by the unihemispheric sleeping behaviour and long-term vigilance. Here, we examined the genes responsible for melatonin synthesis (Aanat and Asmt) and signalling (Mtnr1a and Mtnr1b) in 12 toothed and baleen whale genomes. Based on an ample genomic comparison, we deduce that melatonin-related gene modules are eroded in Cetacea.