Postnatal Ontogeny of the Circadian Expression of the Adrenal Clock Genes and Corticosterone Rhythm in Male Rats

Abstract

The postnatal synchronization of the circadian variation of the adrenal clock genes in mammals remains unknown. We evaluated the postnatal ontogeny of daily variation of clock genes (Clock/Bmal1/Per1/Per2/Per3/Cry1/Cry2/Rorα/Rev-Erbα) and steroidogenesis-related genes (Star and Mc2r) in rat adrenals and its relationship with the emergence of plasma corticosterone rhythm using cosinor analysis. Plasma corticosterone circadian rhythm was detected from postnatal day (P)1, with morning acrophase, between zeitgeber time (ZT)0 and ZT2. From P14, there was a nocturnal acrophase of corticosterone at ZT20, which was associated with pups' eye opening. From P3 there was a circadian variation of the mRNA expression of Bmal1, Per2, Per3, and Cry1 genes with morning acrophase, whereas Rev-Erbα had nocturnal acrophase. From P14, Bmal1, Per2, Per3, and Cry1 acrophases advanced by approximately 10 hours, as compared with early neonatal days, becoming vespertine-nocturnal. In all postnatal ages, Per2 and Cry1 circadian profiles were synchronized in phase with the circadian rhythm of plasma corticosterone, whereas Bmal1 was in antiphase. An adult-like Star circadian rhythm profile was observed only from P21. In conclusion, our original data demonstrated a progressive postnatal maturation of the circadian variation of the adrenal clock genes in synchrony with the development of the corticosterone circadian rhythm in rats.

MECHANISMS IN ENDOCRINOLOGY: A sense of time of the glucocorticoid circadian clock: from the ontogeny to the diagnosis of Cushing’s syndrome

“…We also demonstrated circadian variations, as well as a morning acrophase, in the mRNA expression of Bmal1, Per2, Per3 and Cry1 genes from P3, whereas Rev-Erbα presented a nocturnal acrophase. From P14, Bmal1, Per2, Per3 and Cry1 acrophases advanced by approximately 10 h compared to early neonatal periods and became vespertine nocturnal (103), which was consistent with the adult circadian profile as previously described for adult rat adrenal glands (36).…”

“…In addition to light, daily patterns of food ingestion and motor activity can also act as synchroniser agents in adult rats. Taken together, these data suggest that rats exhibit a progressive postnatal maturation of circadian variations in adrenal clock genes, which is in synchrony with the development of the plasma corticosterone circadian rhythm (103).…”

“…Accordingly, such an event had been found to occur on postnatal days P30, P22, P21 or P16 (11,12,101,102). Applying appropriate protocols and using cosinor-based rhythmometry, we had recently conducted a refined study on the emergence of rat postnatal corticosterone rhythm and its relationship with the adrenal rhythmicity of Clock, Bmal1, Per1, Per2, Per3, Cry1, Cry2 and Rorα/Rev-Erbα genes and steroidogenesis-related genes (Star and Mc2r) in rats from the early postnatal period until adulthood (103). In our study, rat pups at postnatal ages P1, P3, P6, P12, P14, P16, P21 and P24 were decapitated at 4-h intervals over a 24-h period.…”

“…4). Considering that rat SCN maturation and clock gene expression rhythmicity are completed only after P10 (86), we hypothesised that the external rhythmic cues for pups before P10 may have been derived from the maternal environment, entraining the circadian rhythm of adrenal clock genes and corticosterone secretion (103). Although adult rat activity is predominantly nocturnal, mothers approach the litter to feed their pups during the light phase.…”

Circadian alignment in a foster mother improves the offspring's pathological phenotype

“…) and adrenal tissue (Roa et al . ). The amplitudes of these rhythms reflect the degree of synchrony among individual cellular oscillators that is required for coherent rhythms at the tissue level in vivo .…”