Anna Angelousi1, Eva Kassi2, Narjes Nasiri-Ansari2, Martin O Weickert3,4,5, Harpal Randeva3,4,5, Gregory Kaltsas6. 1. Department of Pathophysiology, Endocrine Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece. 2. Department of Biochemistry, National and Kapodistrian University of Athens, Athens, Greece. 3. Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK. 4. Division of Translational and Experimental Medicine, Warwick Medical School, University of Warwick, Coventry, UK. 5. Centre for Applied Biological & Exercise Sciences, Coventry University, Coventry, UK. 6. 1st Department of Propaedeutic Internal Medicine, Medical School, Laikon Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Abstract
BACKGROUND: Various endocrine signals oscillate over the 24-hour period and so does the responsiveness of target tissues. These daily oscillations do not occur solely in response to external stimuli but are also under the control of an intrinsic circadian clock. DESIGN: We searched the PubMed database to identify studies describing the associations of clock genes with endocrine diseases. RESULTS: Various human single nucleotide polymorphisms of brain and muscle ARNT-like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK) genes exhibited significant associations with type 2 diabetes mellitus. ARNTL2 gene expression and upregulation of BMAL1 and PER1 were associated with the development of type 1 diabetes mellitus. Thyroid hormones modulated PER2 expression in a tissue-specific way, whereas BMAL1 regulated the expression of type 2 iodothyronine deiodinase in specific tissues. Adrenal gland and adrenal adenoma expressed PER1, PER2, CRY2, CLOCK and BMAL1 genes. Adrenal sensitivity to adrenocorticotrophin was also affected by circadian oscillations. A significant correlation between the expression of propio-melanocorticotrophin and PER 2, as well as between prolactin and CLOCK, was found in corticotroph and lactosomatotroph cells, respectively, in the pituitary. Clock genes and especially BMAL1 showed an important role in fertility, whereas oestradiol and androgens exhibited tissue-specific effects on clock gene expression. Metabolic disorders were also associated with circadian dysregulation according to studies in shift workers. CONCLUSIONS: Clock genes are associated with various endocrine disorders through complex mechanisms. However, data on humans are scarce. Moreover, clock genes exhibit a tissue-specific expression representing an additional level of regulation. Their specific role in endocrine disorders and their potential implications remain to be further clarified.
BACKGROUND: Various endocrine signals oscillate over the 24-hour period and so does the responsiveness of target tissues. These daily oscillations do not occur solely in response to external stimuli but are also under the control of an intrinsic circadian clock. DESIGN: We searched the PubMed database to identify studies describing the associations of clock genes with endocrine diseases. RESULTS: Various human single nucleotide polymorphisms of brain and muscle ARNT-like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK) genes exhibited significant associations with type 2 diabetes mellitus. ARNTL2 gene expression and upregulation of BMAL1 and PER1 were associated with the development of type 1 diabetes mellitus. Thyroid hormones modulated PER2 expression in a tissue-specific way, whereas BMAL1 regulated the expression of type 2 iodothyronine deiodinase in specific tissues. Adrenal gland and adrenal adenoma expressed PER1, PER2, CRY2, CLOCK and BMAL1 genes. Adrenal sensitivity to adrenocorticotrophin was also affected by circadian oscillations. A significant correlation between the expression of propio-melanocorticotrophin and PER 2, as well as between prolactin and CLOCK, was found in corticotroph and lactosomatotroph cells, respectively, in the pituitary. Clock genes and especially BMAL1 showed an important role in fertility, whereas oestradiol and androgens exhibited tissue-specific effects on clock gene expression. Metabolic disorders were also associated with circadian dysregulation according to studies in shift workers. CONCLUSIONS:Clock genes are associated with various endocrine disorders through complex mechanisms. However, data on humans are scarce. Moreover, clock genes exhibit a tissue-specific expression representing an additional level of regulation. Their specific role in endocrine disorders and their potential implications remain to be further clarified.
Authors: Venkata Naga Srikanth Garikipati; Arsen Arakelyan; Eleanor A Blakely; Polly Y Chang; May M Truongcao; Maria Cimini; Vandana Malaredy; Anamika Bajpai; Sankar Addya; Malik Bisserier; Agnieszka Brojakowska; Abrisham Eskandari; Mary K Khlgatian; Lahouaria Hadri; Kenneth M Fish; Raj Kishore; David A Goukassian Journal: Cells Date: 2021-02-13 Impact factor: 7.666
Authors: Francesca Sciarra; Edoardo Franceschini; Federica Campolo; Daniele Gianfrilli; Francesco Pallotti; Donatella Paoli; Andrea M Isidori; Mary Anna Venneri Journal: Int J Mol Sci Date: 2020-05-30 Impact factor: 5.923