Melatonin replacement restores the circadian behavior in adult rat Leydig cells after pinealectomy

Baburski, Aleksandar Z.; Sokanovic, Srdjan J.; Janjic, Marija M.; Stojkov-Mimic, Natasa J.; Bjelic, Maja M.; Andrić, Silvana A.; Kostic, Tatjana S.

doi:10.1016/j.mce.2015.05.039

Cited by 41 publications

(39 citation statements)

References 51 publications

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“…Melatonin is known to promote stem cell proliferation and differentiation [ 39 – 41 ]. In addition, melatonin is involved in the function of the male reproductive system, particularly the testes, since Leydig cells are sensitive to melatonin [ 42 , 43 ]. The simultaneous administration of melatonin with the transplantation of spermatogonial stem cells in azoospermia mouse testes increases the efficiency of transplantation and improves the structural properties of the testis tissue [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Melatonin up-regulates the expression of the GATA-4 transcription factor and increases testosterone secretion from Leydig cells through RORα signaling in anin vitrogoat spermatogonial stem cell differentiation culture system

Deng

Zhang

et al. 2017

Oncotarget

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Because androgen function is regulated by its receptors, androgen-androgen receptor signaling is crucial for regulating spermatogenesis. Androgen is mainly testosterone secreted by testis. Based on the results of early studies in goats, the administration of melatonin over an extended period of time increases steroid production, but the underlying mechanism remains unclear. Here, we report the expression of the melatonin membrane receptors MT1 and MT2 and the retinoic acid receptor-related orphan receptor-alpha (RORα) in the goat testis. An in vitro differentiation system using spermatogonial stem cells (SSCs) cultured in the presence of testicular somatic cells was able to support the formation of sperm-like cells with a single flagellum. The addition of 10-7 M melatonin to the in vitro culture system increased RORα expression and considerably improved the efficiency of haploid cell differentiation, and the addition of the RORα agonist CGP52608 significantly increased the testosterone concentration and expression of GATA binding factor 4 (GATA-4). Furthermore, inhibitors of melatonin membrane receptors and a RORα antagonist (T0901317) also led to a considerable reduction in the efficiency of haploid spermatid formation, which was coupled with the suppression of GATA-4 expression. Based on these results, RORα may play a crucial role in enhancing melatonin-regulated GATA-4 transcription and steroid hormone synthesis in the goat spermatogonial stem cell differentiation culture system.

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Section: Discussionmentioning

confidence: 99%

Melatonin up-regulates the expression of the GATA-4 transcription factor and increases testosterone secretion from Leydig cells through RORα signaling in anin vitrogoat spermatogonial stem cell differentiation culture system

Deng

Zhang

et al. 2017

Oncotarget

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“…Results from the present study strongly suggest circadian time as the critical element in determining the stress response. Namely, in Leydig cells, genes responsible for testosterone production ( Star, Cyp11a1 , and Cyp17a1 ) together with canonical clock genes ( Bmal1, Per1/2/3, Cry1/2, Rev-erba / b, Rorb, Dec1/2, Dbp , and E4bp4 ) are expressed in a circadian manner (Baburski et al, 2016, 2015). However, these genes’ expression pattern is changed due to stress and varies depending on the time of the stressful event.…”

Section: Discussionmentioning

confidence: 99%

“…IMO potentiates the expression of Bmal1 /BMAL1 and Per1/2 /PER1 and Rev-erba , suggesting that stressful stimuli can entrain the clock in the Leydig cells. Further, BMAL1 is cyclically expressed in the rat (Baburski et al, 2019, 2015) and mouse (Chen et al, 2017) Leydig cells, stimulating StAR expression (Alvarez et al, 2008), therefore contributing to the cyclic expression of StAR protein. Since IMO in the dark phase promotes BMAL1, this may mitigate the effects of stress on steroidogenesis during the night.…”

Section: Discussionmentioning

confidence: 99%

Stress alters the activity of Leydig cells dependently on the diurnal time

Medar

Andrić

Kostic

2021

Preprint

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The connection between two fundamental processes in cells, the stress response and circadian timekeeping, were analyzed on Leydig cells from stressed rats. Stress increased glucocorticoids and decreased testosterone blood level. Transcriptional analysis revealed different sensitivity to stress events depending on the circadian time: the majority of steroidogenesis-related genes (Lhcgr, Nr3c1, Cyp11a1, Cyp17a1, Hsd3b1/2) were down-regulated by stress in the inactive (light) phase, but in the active (dark) phase of the day, they were unchanged or even up-regulated. Stress potentiates the expression of clock elements Bmal1/BMAL1, Per1/2/PER1, and Rev-erba. Glucocorticoid-treated rats showed a similar response, likewise stress on the negative clock regulators (Rev-erba/b, Cry1/2, Per1/2), suggesting that stress-induced glucocorticoids regulate clock loops but also outside genes through E-/RORE-box. Blockade of intratesticular glucocorticoid receptors prevented stress-induced change in expression negative clock regulators. The results reveal glucocorticoid-mediated communication between the stress- and circadian-system resets the Leydig cell's clock.

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“…Melatonin is involved in the function of the male reproductive system, particularly in the testes, since Leydig cells are sensitive to melatonin [ 30 , 31 ]. Melatonin regulates androgen secretion through a melatonin membrane receptor in Leydig cells [ 32 ].…”

Section: Melatonin Regulates Leydig Cell–testosterone Secretionsmentioning

confidence: 99%

Melatonin Regulates the Synthesis of Steroid Hormones on Male Reproduction: A Review

Deng

Sun

et al. 2018

Molecules

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Melatonin is a ubiquitous molecule and exhibits different effects in long-day and short-day breeding animals. Testosterone, the main resource of androgens in the testis, is produced by Leydig cells but regulated mainly by cytokine secreted by Sertoli cells. Melatonin acts as a local modulator of the endocrine activity in Leydig cells. In Sertoli cells, melatonin influences cellular proliferation and energy metabolism and, consequently, can regulate steroidogenesis. These suggest melatonin as a key player in the regulation of steroidogenesis. However, the melatonin-induced regulation of steroid hormones may differ among species, and the literature data indicate that melatonin has important effects on steroidogenesis and male reproduction.

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Melatonin replacement restores the circadian behavior in adult rat Leydig cells after pinealectomy

Cited by 41 publications

References 51 publications

Melatonin up-regulates the expression of the GATA-4 transcription factor and increases testosterone secretion from Leydig cells through RORα signaling in anin vitrogoat spermatogonial stem cell differentiation culture system

Melatonin up-regulates the expression of the GATA-4 transcription factor and increases testosterone secretion from Leydig cells through RORα signaling in anin vitrogoat spermatogonial stem cell differentiation culture system

Stress alters the activity of Leydig cells dependently on the diurnal time

Melatonin Regulates the Synthesis of Steroid Hormones on Male Reproduction: A Review

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