Role of adrenal and ovarian steroids on the entrainment mechanism of the biological clock

Abstract

Circadian clocks enable organisms to anticipate and synchronize their behavior and physiology to periodic changes in the photoperiod. A transcriptional-translational autoregulatory loop of genes generally referred as clock genes is the basic molecular mechanism of the circadian clock. In mammals, although these clock genes are also present in several peripheral organs, the suprachiasmatic nucleus (SCN), the central clock, is the driver of circadian rhythm observed in different physiological processes and behaviors. However the mechanisms involved in the transmission of the circadian signal from the SCN to peripheral tissues are not complete understood. Since glucocorticoids are secreted from adrenal glands in a circadian fashion, and the estradiol induces a circadian release of luteinizing hormone from anterior pituitary, we propose that glucocorticoid and estradiol are part of these mechanisms, modulating the circadian clock in peripheral tissue. Considering that cultured cells may constitute models of peripheral clocks, we will evaluated the effects of glucocorticoids and estradiol on the 24-h expression of clock genes in B-16 F10 murine melanoma, a model for studies of skin pigment cells, as well as in GT1-7 cell, a mouse hypothalamic cell line used as a model for gonadotropin-releasing hormone secretion. These will be tested by the quantification of luciferin bioluminescence originated from the activation of luciferase located in period (Per1, one of the clock genes) promoter, as well as quantification of endogenous expression of clock-gene transcripts and proteins in these cells.