
doi: 10.1111/eci.12927
pmid: 29577261
AbstractBackgroundVarious 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.DesignWe searched the PubMed database to identify studies describing the associations of clock genes with endocrine diseases.ResultsVarious 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.ConclusionsClock 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.
Circadian Rhythm Signaling Peptides and Proteins, Lactotrophs, Adrenal Gland Neoplasms, ARNTL Transcription Factors, CLOCK Proteins, Iodothyronine Deiodinase Type II, Period Circadian Proteins, Endocrine System Diseases, Iodide Peroxidase, Polymorphism, Single Nucleotide, Thyroid Diseases, Somatotrophs, Prolactin, Cryptochromes, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Adrenocortical Adenoma, Humans, Genetic Predisposition to Disease, Corticotrophs
Circadian Rhythm Signaling Peptides and Proteins, Lactotrophs, Adrenal Gland Neoplasms, ARNTL Transcription Factors, CLOCK Proteins, Iodothyronine Deiodinase Type II, Period Circadian Proteins, Endocrine System Diseases, Iodide Peroxidase, Polymorphism, Single Nucleotide, Thyroid Diseases, Somatotrophs, Prolactin, Cryptochromes, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Adrenocortical Adenoma, Humans, Genetic Predisposition to Disease, Corticotrophs
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