Potential Effect of the Circadian Clock on Erectile Dysfunction

Abstract

The circadian rhythm is an internal timing system, which is generated by circadian clock genes. Because the circadian rhythm regulates numerous cellular, behavioral, and physiological processes, organisms have evolved with intrinsic biological rhythms to adapt the daily environmental changes. A variety of pathological events occur at specific times, while disturbed rhythms can lead to metabolic syndrome, vascular dysfunction, inflammatory disorders, and cancer. Therefore, the circadian clock is considered closely related to various diseases. Recently, accumulated data have shown that the penis is regulated by the circadian clock, while erectile function is impaired by an altered sleep-wake cycle. The circadian rhythm appears to be a novel therapeutic target for preventing and managing erectile dysfunction (ED), although research is still progressing. In this review, we briefly summarize the superficial interactions between the circadian clock and erectile function, while focusing on how disturbed rhythms contribute to risk factors of ED. These risk factors include NO/cGMP pathway, atherosclerosis, diabetes mellitus, lipid abnormalities, testosterone deficiency, as well as dysfunction of endothelial and smooth muscle cells. On the basis of recent findings, we discuss the potential role of the circadian clock for future therapeutic strategies on ED, although further relevant research needs to be performed.

Sleep and circadian rhythm disturbance in kidney stone disease: a narrative review

“…It synchronizes with Earth’s time and feeds back to the downstream brain and peripheral regions by sympathetic nervous system transduction and hormone secretion after light signals from the light-dark cycle are received by the retina and transmitted to the SCN as electrical signals ( 10 , 24 ). Some synchronization factors also called “time givers” or zeitgebers vary with temperature, diet, pharmacological manipulation, and social interactions ( 25 ). Additionally, peripheral organs, including the heart, liver, and kidney, participate in the “peripheral clock” and regulate cyclic physiological functions by manipulating the transcription of circadian genes, protein synthesis, energy metabolism, and so on.…”

“…At the molecular level, approximately 10% of genes are clock-controlled genes (CCGs) with circadian oscillations, also called circadian clock genes. The maintenance of circadian rhythm depends on a transcription-translation negative feedback loop formed by a series of interacting clock genes ( 25 , 27 , 28 ) (see Figure 1 ). The cycle of potential molecular mechanisms generating circadian rhythm is approximately 24 hours without synchronizing input; the central-peripheral network can adapt to a limited range of day lengths ( 29 , 30 ).…”

“…Additionally, IH disrupts endothelial NO expression by promoting ROS generation. Endothelial dysfunction is mainly caused by inhibited NO bioactivity and bioavailability impairs vascular vasodilation and enhances vasoconstriction ( 25 , 136 ).…”

Circadian disturbance induces erectile dysfunction by impairing endothelial function

“… 4 5 6 7 This is called circadian rhythm 4 5 6 7 which is essential to maintain physiological functions and guarantee optimal performance for organisms. 6 7 At molecular level for circadian system, 8 9 the circadian locomotor output cycles kaput (CLOCK) and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) polymerize the positive complex to activate transcription of other clock genes (such as period 1/2/3 [ PER1/2/3 ], cryptochrome 1/2 [ CRY1/2 ], retinoic acid-related orphan nuclear receptor [ REV-ERB ], and retinoic acid-related orphan receptor [ ROR ]) and clock-controlled genes. 10 11 PER and CRY accumulate in the cytoplasm and translocate to the nucleus to restrict the activity of CLOCK/BMAL1, forming the main negative feedback loop.…”

Morphofunctional Changes in Rat Testes During Premature Aging Caused by Dark Deprivation

“…Темновая депривация оказывает негативное влияние на репродуктивное здоровье населения, в том числе на дифференцировку мужских половых клеток, приводя к преждевременному старению и мужскому бесплодию [2,4]. Одним из факторов, приводящий к развитию морфофункциональных нарушений органов мужской репродуктивной системы на фоне темновой депривации является дефицит выработки мелатонина.…”