Modulation of bone morphogenetic protein activity by melatonin in ovarian steroidogenesis

Otsuka, Fumio

doi:10.1002/rmb2.12089

Cited by 16 publications

(7 citation statements)

References 57 publications

(142 reference statements)

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“…It is not only present in the blood but also in body fluids, including cerebrospinal fluid, follicular fluid, and seminal vesicle fluid [3]. Melatonin receptors are found in numerous organs, and in addition to their own biorhythms, they determine, via several signaling mechanisms, secretion of various hormones, immune functions, lipid and glucose metabolism, as well as bone metabolism [4][5][6][7][8][9]. These rhythms are involved in aging, carcinogenesis, and a number of diseases [4,[10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

Tamura

Jozaki

Tanabe

et al. 2020

IJMS

140

105

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Melatonin is probably produced in all cells but is only secreted by the pineal gland. The pineal secretion of melatonin is determined by the light-dark cycle, and it is only released at night. Melatonin regulates biological rhythms via its receptors located in the suprachiasmatic nuclei of the hypothalamus. Melatonin also has strong antioxidant activities to scavenge free radicals such as reactive oxygen species (ROS). The direct free radical scavenging actions are receptor independent. ROS play an important role in reproductive function including in the ovulatory process. However, excessive ROS can also have an adverse effect on oocytes because of oxidative stress, thereby causing infertility. It is becoming clear that melatonin is located in the ovarian follicular fluid and in the oocytes themselves, which protects these cells from oxidative damage as well as having other beneficial actions in oocyte maturation, fertilization, and embryo development. Trials on humans have investigated the improvement of outcomes of assisted reproductive technology (ART), such as in vitro fertilization and embryo transfer (IVF-ET), by way of administering melatonin to patients suffering from infertility. In addition, clinical research has examined melatonin as an anti-aging molecule via its antioxidative actions, and its relationship with the aging diseases, e.g., Alzheimer's and Parkinson's disease, is also underway. Melatonin may also reduce ovarian aging, which is a major issue in assisted reproductive technology. This review explains the relationship between melatonin and human reproductive function, as well as the clinical applications expected to improve the outcomes of assisted reproductive technology such as IVF, while also discussing possibilities for melatonin in preventing ovarian aging.

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Section: Introductionmentioning

confidence: 99%

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

Tamura

Jozaki

Tanabe

et al. 2020

IJMS

140

105

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“…First, it influences the action of LH as its absence through pinealectomy determines a reduction in the ovulation rates [95] as well as intense histological changes, such as low number of luteal bodies, increase in the thecae cells and interstitial cell layers, and presence of microcysts in the periphery of the organ [96,97]. Those changes are similar to the ones observed in the ovaries of patients with polycystic ovarian syndrome [98]. In pinealectomized rats, melatonin administration may partially reverse those changes and restore the luteal bodies [95,97,99].…”

Section: Female Gonadsmentioning

confidence: 73%

The Crosstalk between Melatonin and Sex Steroid Hormones

et al. 2021

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Melatonin, an indolamine mainly released from the pineal gland, is associated with many biological functions namely the modulation of circadian and seasonal rhythms, sleep inducer, regulator of energy metabolism, antioxidant and anticarcinogenic. Although several evidences also recognize the influence of melatonin in the reproductive physiology, the crosstalk between melatonin and sex hormones is not clear. Here, we review the effects of sex differences in the circulating levels of melatonin and update the current knowledge on the link between sex hormones and melatonin. Furthermore, we explore the effects of melatonin on gonadal steroidogenesis and hormonal control in females. The literature review shows that despite the strong evidence that sex differences impact on the circadian profiles of melatonin, reports are still considerably ambiguous and these differences may arise from several factors, like the use of contraceptive pills, hormonal status and sleep deprivation. Furthermore, there has been an inconclusive debate about the characteristics of the reciprocal relationship between melatonin and reproductive hormones. In this regard, there is evidence for the role of melatonin in gonadal steroidogenesis brought about by research that shows that melatonin affects multiple transduction pathways that modulate Sertoli cell physiology and consequently spermatogenesis, and also estrogen and progesterone production. From the outcome of our research, it is possible to conclude that understanding the correlation between melatonin and reproductive hormones is crucial for the correction of several complications occurring during pregnancy, like pre-eclampsia and for the control of climacteric symptoms.

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“…Besides the actions of metformin, we previously reported that melatonin [32], androgen [11], insulin-like growth factor (IGF)-I [12] are key factors that enable to induce Smad6 and/or Smad7 expression. On the contrary, prolactin, somatostatins and incretins were suggested to be suppressors for Smad6/7 in granulosa cells [33]. Thus, a modulatory effect on BMPR signaling mediated by Smad6/7 seems to be crucial for integrating ovarian steroidogenesis via the endogenous BMP activity in granulosa cells.…”

Section: Discussionmentioning

confidence: 96%

Effect of the interaction of metformin and bone morphogenetic proteins on ovarian steroidogenesis by human granulosa cells

Iwata

Hasegawa²,

Fujita³

et al. 2018

Biochemical and Biophysical Research Communications

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In the present study, we studied the effects of metformin and its interactions with the actions of bone morphogenetic proteins (BMPs) on ovarian steroidogenesis. It was revealed that metformin treatment enhanced progesterone production by human granulosa KGN cells and rat primary granulosa cells induced by forskolin and FSH, respectively. In human granulosa cells, it was found that metformin treatment suppressed phosphorylation of Smad1/5/9 activated by BMP-15 compared with that induced by other BMP ligands. Moreover, metformin treatment increased the expression of inhibitory Smad6, but not of that Smad7, in human granulosa cells, while metformin had no significant impact on the expression levels of BMP type-I and -II receptors. Thus, the mechanism by which metformin suppresses BMP-15-induced Smad1/5/9 phosphorylation is likely, at least in part, to be upregulation of inhibitory Smad6 expression in granulosa cells. The results suggest the existence of functional interaction between metformin and BMP signaling, in which metformin enhances progesterone production by downregulating endogenous BMP-15 activity in granulosa cells.

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Modulation of bone morphogenetic protein activity by melatonin in ovarian steroidogenesis

Cited by 16 publications

References 57 publications

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

The Crosstalk between Melatonin and Sex Steroid Hormones

Effect of the interaction of metformin and bone morphogenetic proteins on ovarian steroidogenesis by human granulosa cells

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