RESUMOA melatonina é um hormônio produzido pela glândula pineal, cuja secreção está diretamente relacionada ao ciclo claroescuro. É um poderoso antioxidante e tem papel fundamental na regulação do estado sono/vigília, do ritmo de vários processos fisiológicos, participando do controle do relógio biológico, inclusive nos seres humanos. Ressalta-se que há evidências da sua ação no sistema genital feminino, influenciando a função ovariana e a fertilidade. De fato, este hormônio interage com esteróides sexuais, como o estrogênio, modificando a sinalização celular e a resposta no tecido alvo. Estudos clínicos sugerem que o tratamento com a melatonina interviria com a evolução de neoplasia-dependente do estrogênio. O objetivo dessa revisão é analisar as principais ações da melatonina no sistema neuroendócrino, no ciclo sono-vigília, no sistema imunológico, no sistema cardiovascular, bem como no sistema reprodutor. UNITERMOS INTRODUÇÃOA melatonina é uma indolamina produzida pela glândula pineal, que está localizada no teto do terceiro ventrículo entre os dois hemisférios cerebrais. Pesa aproximadamente 0,13 gramas e possui aproximadamente 1,2 cm de diâmetro, originando-se do diencéfalo. É órgão endócrino ativo, conectado à retina pelas projeções retino-hipotalâmicas via núcleo supraquiasmático do hipotálamo, no qual funciona como um controle autônomo para o gânglio cervical superior, de onde as fibras ganglionares posteriores alcançam finalmente a pineal 1 . Há outras fontes produtoras deste hormônio como a retina, corpo ciliar da íris, glândulas harderianas e lacrimais, linfócitos, intestino grosso e em menor quantidade em outros locais 2,3,4 . Essas outras fontes teriam contribuição mínima para a concentração plasmática da melatonina, porém, seriam importantes para ação local na qual foram produzidas. Essa produção extrapineal justificaria a presença de baixos níveis de 6-sulfatoximelatonina (seu principal metabólito) na urina de ratas que passaram por remoção da glândula pineal 2,3,4 . Salienta-se que o ritmo circadiano e a grande concentração noturna desse hormônio são determinados pela síntese deste hormônio na pineal 2,3,4 . Papel funcional da melatonina na regulação da ritmicidade biológicaA glândula pineal, associadamente aos núcleos supraquiasmáticos hipotalâmicos, constitui parte importante do sistema neuroendócrino, responsável pela organização temporal dos diversos eventos fisiológi-cos e comportamentais 5 . Isso é fundamental para a adaptação do indivíduo e da espécie às flutuações temporais cíclicas do meio ambiente (regulação endócrina e metabólica); regulação do ciclo sono-vigília; regulação do sistema imunológico; regulação cardiovascular, em especial da pressão arterial, bem como no sistema genital 2,34,6,7 . Além disso, a melatonina influencia o ritmo de vários outros processos fisiológicos durante a noite: a digestão torna-se mais lenta, a temperatura corporal cai, o ritmo cardíaco e a pressão sangüínea diminuem e o sistema imunológico é estimulado. Parece ser capaz de aumentar a mobilidade e a ati...

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.

Accorsi-Neto A, Haidar M, Simões R, Simões M, Soares-Jr J, Baracat E. Effects of isoflavones on the skin of postmenopausal women: a pilot study. Clinics. 2009;64(6):505-10. OBJECTIVE:The aim of this study was to evaluate the effects of isoflavones on the skin of postmenopausal women. DESIGN: A prospective study was performed with 30 postmenopausal women before and immediately after the end of treatment with 100 mg/day of an isoflavones-rich, concentrated soy extract for six months. A skin punch was performed in the gluteal region for sample collection before and immediately after the treatment program. Morphometric determination of epidermal thickness, the papillary index (wrinkling), and the amount of dermal elastic and collagen fibers was assessed. In addition, the number of blood vessels in the sample was also evaluated. The paired Student's t-test was used for statistical analysis (P ≤ 0.05). RESULTS: Isoflavone treatment resulted in a 9.46% increase in the thickness of the epidermis in 23 patients. In addition, the papillary index was reduced in 21 women. The papillary index was inversely proportional to skin wrinkling, i.e., there were a large number of papillae after treatment. The amount of collagen in the dermis was increased in 25 women (86.2%). In 22 women (75.8%) we observed that the number of elastic fibers increased. The number of dermal blood vessels was significantly increased in 21 women. CONCLUSION: Our data show that the use of a concentrated, isoflavone-rich soy extract during six consecutive months caused significant increases in epithelial thickness, the number of elastic and collagen fibers, as well as the blood vessels.

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The preliminary results of ovarian transplantation in clinical practice are encouraging. However, the follicular depletion caused by ischemic injury is a main concern and is directly related to short-term graft survival. Cell therapy with adipose tissue-derived stem cells (ASCs) could be an alternative to induce early angiogenesis in the graft. This study aimed to evaluate ASCs therapy in rat cryopreserved ovarian grafts. A single dose of rat ASC (rASCs) or vehicle was injected into the bilateral cryopreserved ovaries of twelve adult female rats immediately after an autologous transplant. Daily vaginal smears were performed for estrous cycle evaluation until euthanasia on postoperative day 30. Follicle viability, graft morphology and apoptosis were assessed. No differences were found with respect to estrous cycle resumption and follicle viability (P > 0.05). However, compared with the vehicle-treated grafts, the morphology of the ASCs-treated grafts was impaired, with diffuse atrophy and increased apoptosis (P < 0.05). ASCs direct injected in the stroma of rat cryopreserved ovarian grafts impaired its morphology although may not interfere with the functional resumption on short-term. Further investigations are necessary to evaluated whether it could compromise their viability in the long-term.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0068-3) contains supplementary material, which is available to authorized users.

BackgroundA major concern in ovarian transplants is substantial follicle loss during the initial period of hypoxia. Adipose tissue-derived stem cells (ASCs) have been employed to improve angiogenesis when injected into ischemic tissue. This study evaluated the safety and efficacy of adipose tissue-derived stem cells (ASCs) therapy in the freshly grafted ovaries 30 days after injection.MethodsRat ASCs (rASCs) obtained from transgenic rats expressing green fluorescent protein (GFP)-(5 × 104 cells/ovary) were injected in topic (intact) or freshly grafted ovaries of 30 twelve-week-old adult female Wistar rats. The whole ovary was grafted in the retroperitoneum without vascular anastomosis, immediately after oophorectomy. Vaginal smears were performed daily to assess the resumption of the estrous cycle. Estradiol levels, grafts morphology and follicular viability and density were analyzed. Immunohistochemistry assays were conducted to identify and quantify rASC-GFP+, VEGF tissue expression, apoptosis (cleaved caspase-3 and TUNEL), and cell proliferation (Ki-67). Quantitative gene expression (qPCR) for VEGF-A, Bcl2, EGF and TGF-β1 was evaluated using RT-PCR and a double labeling immunofluorescence assay for GFP and Von Willebrand Factor (VWF) was performed.ResultsGrafted ovaries treated with rASC-GFP+ exhibited earlier resumption of the estrous phase (p < 0.05), increased VEGF-A expression (11-fold in grafted ovaries and 5-fold in topic ovaries vs. control) and an increased number of blood vessels (p < 0.05) in ovarian tissue without leading to apoptosis or cellular proliferation (p > 0.05). Estradiol levels were similar among groups (p > 0.05). rASC-GFP+ were observed in similar quantities in the topic and grafted ovaries (p > 0.05), and double-labeling for GFP and vWF was observed in both injected groups.ConclusionrASC therapy in autologous freshly ovarian grafts could be feasible and safe, induces earlier resumption of the estrous phase and enhances blood vessels in rats. This pilot study may be useful in the future for new researches on frozen-thawed ovarian tissue.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-015-0104-2) contains supplementary material, which is available to authorized users.

The role of prolactin on breast cancer development and progression is debated. Breast cancer progression largely depends on cell movement and on the ability to remodel the actin cytoskeleton. In this process, actin-binding proteins are requested to achieve fibrillar actin de-polymerization and relocation at the cell membrane. Kinases such as focal adhesion kinase (FAK) are later required to form actin/vinculin-enriched structures called focal adhesion complexes, which mediate firm adhesion to the extracellular matrix. These controllers are regulated by c-Src, which forms multiprotein signaling complexes with membrane receptors and is regulated by a number of hormones, including ­prolactin. We here show that breast cancer cells exposed to prolactin display an elevated c-Src expression and phosphorylation. In parallel, increased moesin and FAK expression and phosphorylation are found. These molecular changes are associated to relocation to the plasma membrane of cytoskeletal actin fibers and to increased horizontal cell movement. In conclusion, prolactin regulates actin remodeling and enhances breast cancer cell movement. This finding broadens the understanding of prolactin actions on breast cancer cells, highlighting new pathways that may be relevant to on breast cancer progression.

Disturbances in endometrial apoptosis may be a contributing factor in patients with idiopathic infertility and recurrent pregnancy loss.