The Effect of CRH and Its Inhibitor, Antalarmin, on in Vitro Growth of Preantral Mouse Follicles, Early Embryo Development, and Steroidogenesis

Dinopoulou, Vasiliki; Partsinevelos, George A.; Mavrogianni, Despina; Anagnostou, Elli; Drakakis, Peter; Makrigiannakis, Antonis; Chrousos, George P.; Loutradis, Dimitris

doi:10.1210/en.2012-1838

Cited by 14 publications

(14 citation statements)

References 29 publications

(27 reference statements)

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“…This study focused on the functions of stress-related hormones to elucidate the link between stress responses and the effect on activation of primordial follicles. Among the hormones studied, CRH is a neuropeptide caused by stress, which also played an important role in regulating ovarian functions and follicle development[ 30 – 32 ]. It was found that the serum CRH level in the CRS 8w group was significantly higher compared with that in the control group ( Fig 1F ).…”

Section: Resultsmentioning

confidence: 99%

Chronic restraint stress induces excessive activation of primordial follicles in mice ovaries

Xu¹,

Sun²,

Wang³

et al. 2018

PLoS ONE

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Chronic stress is an important factor influencing people’s health. It usually causes endocrinal disorders and a decline in reproduction in females. Although studies of both human and animals suggest a detrimental effect of stress on reproduction, the influence of chronic stress on the ovarian reservation and follicular development is still not clear. In this study, a chronic restraint stress (CRS) mouse model was used to investigate the effect of stress on ovarian reservation and follicular development and explore the underlying mechanism. In this study, after 8 weeks of CRS, primordial follicles were excessively activated in the ovaries of the CRS group compared with the control group. Further results showed that the activation of primordial follicles induced by CRS was involved in the increasing expression level of Kit ligand and its receptor Kit and the activation of phosphatidylinositol 3-kinase (PI3K)/phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/protein kinase B (Akt) pathway. The corticotropin-releasing hormone (CRH) is a neuropeptide released due to stress, which plays an important role in regulating follicle development. A high level of serum CRH was detected in the CRS mouse model, and the real-time polymerase chain reaction assay showed that the mRNA level of its main receptor CRHR1increased in the ovaries of the CRS mouse group. Moreover, 100nM CRH significantly improved the activation of primordial follicles in newborn mouse ovaries in vitro. These results demonstrated that CRS could induce immoderate activation of primordial follicles accompanied by the activation of Kit-PI3K signaling, in which CRH might be an important endocrine factor.

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Section: Resultsmentioning

confidence: 99%

Chronic restraint stress induces excessive activation of primordial follicles in mice ovaries

Xu¹,

Sun²,

Wang³

et al. 2018

PLoS ONE

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“…There is evidence that this system exists in ovarian compartments of other species, including humans [58]. Moreover, its actions may vary between follicles and corpora lutea, or between ligand-R1 and –R2 systems [59, 60]. …”

Section: Luteotropic Factors: Luteinizing Hormone (Lh) and Lh-indmentioning

confidence: 99%

Endocrine and local control of the primate corpus luteum

Stouffer

Bishop

Bogan

et al. 2013

Reproductive Biology

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The primate corpus luteum is a transient endocrine gland that differentiates from the ovulatory follicle midway through the ovarian (menstrual) cycle. Its formation and limited lifespan is critical for fertility, as luteal-derived progesterone is the essential steroid hormone required for embryo implantation and maintenance of intra-uterine pregnancy until the placenta develops. It is well-established that LH and the LH-like hormone, CG, are the vital luteotropic hormones during the menstrual cycle and early pregnancy, respectively. Recent advances, particularly through genome analyses and cellular studies, increased our understanding of various local factors and cellular processes associated with the development, maintenance and repression of the corpus luteum. These include paracrine or autocrine factors associated with angiogenesis (e.g., VEGF), and that mediate LH/CG actions (e.g., progesterone), or counteract luteotropic effects (i.e., local luteolysis; e.g., PGF2α). However, areas of mystery and controversy remain, particularly regarding the signals and events that initiate luteal regression in the non-fecund cycle. Novel approaches capable of gene “knockdown” or amplification”, in vivo as well as in vitro, should identify novel or underappreciated gene products that are regulated by or modulate LH/CG actions to control the functional lifespan of the primate corpus luteum. Further advances in our understanding of luteal physiology will help to improve or control fertility for purposes ranging from preservation of endangered primate species to designing novel ovary-based contraceptives and treating ovarian disorders in women. R01 HD020869, R01 HD042000, U54 HD018185, U54 HD055744, P51 OD011092, T32 HD007133, Bayer Schering Pharma AG.

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“…Dinopolou and coworkers (Dinopoulou et al 2013) have reported that both Crhr1 and Crhr2 mRNA were detected in mouse preantral follicles, but the Crhr1 expression was significantly higher than that of Crhr2. Our results show that only CRHR1 is expressed in the porcine ovary, whereas CRHR2 mRNA is not detected.…”

Section: Sp1 Is Involved In Crh Signaling Pathway In Regulating E2 Symentioning

confidence: 95%

“…It is thought that CRH has negative effects on ovary steroidogenesis (Calogero et al 1996, Dinopoulou et al 2013. To confirm the CRH functions in porcine granulosa cells, the cultured cells were treated with CRH for 12 h. The results showed that 100 nM CRH decreased E2 level by 42% in the culture medium.…”

Section: Both Mir-375 and Crh Negatively Regulate E2 Synthesismentioning

confidence: 99%

“…There are reports that CRH also performs functions in nervous system (Chen et al 2005a(Chen et al , 2014, immune system (Karalis et al 1991, Crofford et al 1992, metabolic system (Carlin et al 2006, Huising et al 2010, Stengel & Tache 2014 and reproduction system (Polkowska & Przekop 1997, Erden et al 1998. It is documented that CRH and its receptors have been detected in testis (Yoon et al 1988), the ovary (Mastorakos et al 1993) and the uterus (Makrigiannakis et al 1995, Zoumakis et al 1996, which suggests that CRH could directly affect the gonadal functions, including the development of germ cells and steroidogenesis in both male and female gonads (Ulisse et al 1989, Ghizzoni et al 1997, Kiapekou et al 2011, Dinopoulou et al 2013. However, the mechanism of CRH affecting steroidogenesis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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miR-375 mediates CRH signaling pathway in inhibiting E2 synthesis in porcine ovary

Yu¹,

Li²,

Wang³

et al. 2017

Reproduction

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The corticotropin-releasing hormone (CRH) signaling system is involved in numbers of stress-related physiological and pathological responses，including its inhibiting effects on estradiol (E2) synthesis and follicular development in the ovary. In addition, there are reports that microRNAs (miRNAs) can control the function of animal reproductive system. The aim of present study was to investigate the functions of miR-375 and the relationship between miR-375 and CRH signaling molecules in the porcine ovary. First, our common PCR results show that miR-375 and the CRH receptor 1 (CRHR1) are expressed in porcine ovary, whereas CRH receptor 2 (CRHR2) is not detected. We further have located the cell types of miR-375 and CRHR1 by in situ hybridization (ISH), and the results show that miR-375 is located only in the granulosa cells, whereas CRHR1 is positive in all of granulosa cells and oocytes, inferring that miR-375 and CRHR1 are co-localized in granulosa cells. Second, we show that overexpression of miR-375 in cultured granulosa cells suppresses the E2 production, while miR-375 knockdown demonstrates the opposite result. Besides, our in vitro results demonstrate that miR-375 mediates the signaling pathway of CRH inhibiting E2 synthesis. Finally, our data show that the action of miR-375 is accomplished by directly binding to the 3'UTR of specificity protein1 (SP1) mRNA to decrease the SP1 protein level. Thus, we conclude that miR-375 is a key factor in regulating E2 synthesis by mediating the CRH signaling pathway.

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The Effect of CRH and Its Inhibitor, Antalarmin, on in Vitro Growth of Preantral Mouse Follicles, Early Embryo Development, and Steroidogenesis

Cited by 14 publications

References 29 publications

Chronic restraint stress induces excessive activation of primordial follicles in mice ovaries

Chronic restraint stress induces excessive activation of primordial follicles in mice ovaries

Endocrine and local control of the primate corpus luteum

miR-375 mediates CRH signaling pathway in inhibiting E2 synthesis in porcine ovary

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