![]() Īt the molecular level, circadian clocks operate through a core transcriptional negative feedback loop plus auxiliary feedback loops. The SCN controls circadian rhythms in synchrony with the earth’s rotation and the peripheral biological clock relays the signal to peripheral organs, allowing animals to adapt their feeding, activity, and metabolism to daily environmental changes. The circadian clock encompasses a “master clock” within the hypothalamic suprachiasmatic nucleus (SCN) and “peripheral clocks” within other tissues. Mammalian circadian rhythms regulate many physiological, biological, and behavioral processes. Therefore, Per1/Per2 disruption reduced testosterone synthesis and sperm motility by affecting the PKA-StAR pathway, leading to decreased fertility. Western-blotting showed that steroid acute regulatory protein (StAR) and p-CREB, PKA and AC1 were reduced in testicular tissue of DKO mice compared to WT. Seleno-compound metabolic loci, Scly and Sephs2, were up-regulated and Slc7a11 and Selenop were down-regulated. Spermatogenesis genes, Tubd1 and Pafah1b were down-regulated, influencing tubulin dynamics and leading to impaired motility. Transcriptomic analysis of testicular tissue showed the down-regulation of testosterone synthesis-related enzymes (Cyp11a1, Cyp17a1, Hsd17b3, Hsd3b1, and Star) in the steroid hormone synthesis pathway. Hormone-targeted metabolomics showed reduced plasma levels of free testosterone in DKO male mice compared with WT male mice. ![]() The sperm motility and spermatogenic capacity of male DKO mice were weak. The current study reports that the mechanism of Per1/Per2 Double knockout (DKO) reduced the reproductive capacity of elderly male mice. doi: 10.1016/j.yfrne.2013.11.001.Circadian rhythm disorders caused by genetic or environmental factors lead to decreased male fertility but the mechanisms are poorly understood. Gonadal steroid hormones and the hypothalamo-pituitary-adrenal axis. Corticosteroid feedback control of ACTH secretion: effect of stress-induced corticosterone ssecretion on subsequent stress responses in the rat. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity. Assessment of HPA-axis function in posttraumatic stress disorder: pharmacological and non-pharmacological challenge tests, a review. doi: 10.1002/cphy.c130036.ĭe Kloet CS, Vermetten E, Geuze E, Kavelaars A, Heijnen CJ, Westenberg HG. Hypothalamic-pituitary-adrenocortical axis: neuropsychiatric aspects. In summary, these findings showed that disruption of the circadian system via Per2 gene deletion dysregulated the HPA stress axis and is subsequently correlated with increased depressive-like behaviors and deficits in startle response.Ĭircadian Corticosterone Depression Per2 Startle response. Per2-/- mice had deficits in ASR and PPI startle responses compared to WT mice. In the FST, Per2-/- mice spent more time floating (less time struggling) than WT mice, suggesting increased depressive-like behaviors. There were no changes in expression of any other pituitary or adrenal gene. Per2-/- mice had enhanced CORT levels and adrenal melanocortin receptor 2 (Mc2R) mRNA expression following restraint. Unlike wild-type (WT) mice, Per2 knockout (Per2) mice showed no diurnal rise in CORT levels at the onset of the dark cycle. The present results showed that Per2 knockout impacted CORT levels, mRNA expression, depressive-like behaviors, ASR and PPI. ![]() Mice were tested for depressive-like behaviors (forced swim test (FST)), acoustic startle response (ASR), and pre-pulse inhibition (PPI). Additionally, CORT levels as well as pituitary and adrenal mRNA expression were measured following a mild restraint stress. To study this, corticosterone (CORT) levels were measured through the transition from light (inactive phase) to dark (active phase). One way to address this question is to delete a gene involved in regulating a central circadian gene such as Per2 in an animal model and to determine how this deletion may affect the HPA axis and behaviors that are altered when the HPA axis is dysregulated. Therefore, it is important to understand how disruption of the circadian rhythm alters the HPA axis. Dysregulation of the HPA axis is associated with neuropsychiatric disorders. Circadian control of the hypothalamus-pituitary-adrenal (HPA) axis is critical for regulation of hormones involved in the stress response. The Period Circadian Regulator 2 (Per2) gene is important for the modulation of circadian rhythms that influence biological processes. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |