Effects of melatonin on histomorphology and on the expression of steroid receptors, VEGF, and PCNA in ovaries of pinealectomized female rats

Romeu, Lucrecia Regina Gomes; Motta, E.L.A.; Maganhin, Carla Cristina; Oshima, Celina T. F.; Fonseca, Marcelle C.; Barrueco, Karina F.; Simões, Ricardo Santos; Pellegrino, Renata; Baracat, Edmund Chada; Soares-Júnior, José Maria

doi:10.1016/j.fertnstert.2010.04.042

Cited by 40 publications

(34 citation statements)

References 31 publications

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“…After 24 hr culture, total RNA was extracted separately from PANC-1 cancer cells of each group by using Trizol Ò (Invitrogen Canada Inc., Burlington, ON, Canada) reagent, following the instructions of manufacturer. A 2 lg of [treated in 8 lL of diethypyrocarbonate (DEPC) water in an Eppendorf tube] sample of total RNA [added 1 lL of 10 mm dNTPmix and 1 lL of 0.5 lg/lL oligo (dt) [12][13][14][15][16][17][18] was denatured by incubation at 65°C for 5 min, and the tube was placed on ice for 2 min, then reverse-transcribed (RT) into complementary DNA (cDNA) using the following procedures. Briefly, the denatured RNA was incubated at 42°C for 2 min with 2 lL of 10 · RT buffer, 4 lL of 25 mm MgCl 2 , 2 lL of 0.1 m dL-Dithiothreitol (DTT), and 1 lL RNaseOUTTM recombinant Rnase inhibitor (50 U/lL) and then 1 lL (50 units) of SuperScriptTM II RT was added and incubated at 42°C for 50 min and terminated at 70°C for 15 min in a total volume of 20 lL; finally, samples were chilled on ice.…”

Section: Rt-pcr Analysismentioning

confidence: 99%

Melatonin prevents human pancreatic carcinoma cell PANC‐1‐induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression

Cui

Peng

et al. 2011

Journal of Pineal Research

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Melatonin is an important natural oncostatic agent, and our previous studies have found its inhibitory action on tumor angiogenesis, but the mechanism remains unclear. It is well known that vascular endothelial growth factor (VEGF) plays key roles in tumor angiogenesis and has become an important target for antitumor therapy. Pancreatic cancer is a representative of the most highly vascularized and angiogenic solid tumors, which responds poorly to chemotherapy and radiation. Thus, seeking new treatment strategies targeting which have anti-angiogenic capability is urgent in clinical practice. In this study, a co-culture system between human umbilical vein endothelial cells (HUVECs) and pancreatic carcinoma cells (PANC-1) was used to investigate the direct effect of melatonin on the tumor angiogenesis and its possible action on VEGF expression. We found HUVECs exhibited an increased cell proliferation and cell migration when co-cultured with PANC-1 cells, but the process was prevented when melatonin added to the incubation medium. Melatonin at concentrations of 1 μm and 1 mm inhibited the cell proliferation and migration of HUVECs and also decreased both the VEGF protein secreted to the cultured medium and the protein produced by the PANC-1 cells. In addition, the VEGF mRNA expression was also down-regulated by melatonin. Taken together, our present study shows that melatonin at pharmacological concentrations inhibited the elevated cell proliferation and cell migration of HUVECs stimulated by co-culturing them with PANC-1 cells; this was associated with a suppression of VEGF expression in PANC-1 cells.

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Section: Rt-pcr Analysismentioning

confidence: 99%

Melatonin prevents human pancreatic carcinoma cell PANC‐1‐induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression

Cui

Peng

et al. 2011

Journal of Pineal Research

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“…In reproductive system, melatonin may interact with sex steroids [13-15]. It is well-known that sex steroid receptors might regulate a variety of physiological responses in the ovary, oviduct and uterus tissue when they are activated [13,16,17].…”

Section: Introductionmentioning

confidence: 99%

“…Not surprisingly, PRA, but not PRB expression, is necessary and sufficient for ovulation process [17]. More recently, melatonin significantly increased P4 as well as the number of total PR in ovarian tissue at proestrus [15]. Otherwise, Soares Jr. et al [7] found a diminution of 6-sulfatoximelatonin (STM) metabolite and PR levels after pinealectomy surgery.…”

Section: Introductionmentioning

confidence: 99%

Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation

Chuffa

Seiva

Fávaro

et al. 2011

Reprod Biol Endocrinol

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BackgroundMelatonin is associated with direct or indirect actions upon female reproductive function. However, its effects on sex hormones and steroid receptors during ovulation are not clearly defined. This study aimed to verify whether exposure to long-term melatonin is able to cause reproductive hormonal disturbances as well as their role on sex steroid receptors in the rat ovary, oviduct and uterus during ovulation.MethodsTwenty-four adult Wistar rats, 60 days old (+/- 250 g) were randomly divided into two groups. Control group (Co): received 0.9% NaCl 0.3 mL + 95% ethanol 0.04 mL as vehicle; Melatonin-treated group (MEL): received vehicle + melatonin [100 μg/100 g BW/day] both intraperitoneally during 60 days. All animals were euthanized by decapitation during the morning estrus at 4 a.m.ResultsMelatonin significantly reduced the plasma levels of LH and 17 beta-estradiol, while urinary 6-sulfatoximelatonin (STM) was increased at the morning estrus. In addition, melatonin promoted differential regulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and melatonin receptor (MTR) along the reproductive tissues. In ovary, melatonin induced a down-regulation of ER-alpha and PRB levels. Conversely, it was observed that PRA and MT1R were up-regulated. In oviduct, AR and ER-alpha levels were down-regulated, in contrast to high expression of both PRA and PRB. Finally, the ER-beta and PRB levels were down-regulated in uterus tissue and only MT1R was up-regulated.ConclusionsWe suggest that melatonin partially suppress the hypothalamus-pituitary-ovarian axis, in addition, it induces differential regulation of sex steroid receptors in the ovary, oviduct and uterus during ovulation.

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“…The interpretation of studies on the in vitro effects of melatonin on steroidogenesis is complicated and seems to depend on cell types (theca or granulosa cells), duration of treatment (acute or long-term response), experimental model (cell culture or follicle culture), species, dose and different culture media (Tamura et al 2009). In vivo studies showed that melatonin stimulates P 4 production both in sheep (Durotoye et al 1997, Vázquez et al 2010) and in rats (Dair et al 2008, Romeu et al 2011, Maganhin et al 2013. These findings are confirmed by results of this study, showing that both P 4 production and corpus luteum growth were impaired in pinealectomised ewes.…”

Section: Discussionmentioning

confidence: 99%

Melatonin deprival modifies follicular and corpus luteal growth dynamics in a sheep model

Manca¹,

Manunta²,

Spezzigu³

et al. 2014

Reproduction

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This study assessed the effect of melatonin deprival on ovarian status and function in sheep. Experimental procedures were carried out within two consecutive breeding seasons. Animals were divided into two groups: pinealectomised (nZ6) and sham-operated (nZ6). The completeness of the pineal gland removal was confirmed by the plasma concentration of melatonin. Ovarian status was monitored by ovarian ultrasonography for 1 year to study reproductive seasonality. Follicular and corpus luteal growth dynamics were assessed during an induced oestrous cycle. As the effects of melatonin on the ovary may also be mediated by its antioxidant properties, plasma Trolox equivalent antioxidant capacity (TEAC) was determined monthly for 1 year. Pinealectomy significantly extended the breeding season (310G24.7 vs 217.5G24.7 days in controls; P!0.05). Both pinealectomised and sham-operated ewes showed a well-defined wave-like pattern of follicle dynamics; however, melatonin deficiency caused fewer waves during the oestrous cycle (4.3G0.2 vs 5.2G0.2; P!0.05), because waves were 1 day longer when compared with the controls (7.2G0.3 vs 6.1G0.3; P!0.05). The mean area of the corpora lutea (105.4G5.9 vs 65.4G5.9 mm 2 ; P!0.05) and plasma progesterone levels (7.1G0.7 vs 4.9G0.6 ng/ml; P!0.05) were significantly higher in sham-operated ewes compared with pinealectomised ewes. In addition, TEAC values were significantly lower in pinealectomised ewes compared with control ones. These data suggest that melatonin, besides exerting its well-known role in the synchronisation of seasonal reproductive fluctuations, influences the growth pattern of the follicles and the steroidogenic capacity of the corpus luteum. Free Italian abstractAn Italian translation of this abstract is freely available at

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Effects of melatonin on histomorphology and on the expression of steroid receptors, VEGF, and PCNA in ovaries of pinealectomized female rats

Cited by 40 publications

References 31 publications

Melatonin prevents human pancreatic carcinoma cell PANC‐1‐induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression

Melatonin prevents human pancreatic carcinoma cell PANC‐1‐induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression

Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation

Melatonin deprival modifies follicular and corpus luteal growth dynamics in a sheep model

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