RODRIGO RODRIGUES MARCONDES
Projetos de Pesquisa
Unidades Organizacionais
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
12 resultados
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- Differences in neonatal exposure to estradiol or testosterone on ovarian function and hormonal levels(2015) MARCONDES, Rodrigo R.; CARVALHO, Katia C.; DUARTE, Daniele C.; GARCIA, Natalia; AMARAL, Vinicius C.; SIMOES, Manuel J.; TURCO, Edson G. Lo; SOARES JR., Jose M.; BARACAT, Edmund C.; MACIEL, Gustavo A. R.Exposure to an excess of androgen or estrogen can induce changes in reproductive function in adult animals that resemble polycystic ovary syndrome in humans. However, considerable differences exist among several types of animal models. Little is known about the molecular features of steroidogenesis and folliculogenesis in the ovaries of rats exposed to different sex steroids as neonates. Here, we evaluated the impact of androgen and estrogen exposure on the ovaries of adult female rats during their neonatal period in the gene expression of Lhr and Cyp17a1, two key players of steroidogenesis. We also assessed hormone levels, folliculogenesis and the theca-interstitial cell population. The study was performed on the second postnatal day in thirty female Wistar rats that were sorted into the following three intervention groups: testosterone, estradiol and vehicle (control group). The animals were euthanized 90 days after birth. The main outcomes were hormone serum levels, ovary histomorphometry and gene expression of Lhr and Cyp17a1 as analyzed via quantitative real-time PCR. We found that exposure to excess testosterone in early life increased the LH and testosterone serum levels, the LH/FSH ratio, ovarian theca-interstitial area and gene expression of Lhr and Cyp17a1 in adult rats. Estrogen induced an increase in the ovarian theca-interstitial area, the secondary follicle population and gene expression of Lhr and Cyp17a1. All animals exposed to the sex steroids presented with closed vaginas. Our data suggest that testosterone resulted in more pronounced reproductive changes than did estrogen exposure. Our results might provide some insight into the role of different hormones on reproductive development and on the heterogeneity of clinical manifestations of conditions such as polycystic ovary syndrome.
- Metoclopramide-induced hyperprolactinemia effects on the pituitary and uterine prolactin receptor expression(2013) AMARAL, Vinicius C.; MACIEL, Gustavo A. R.; CARVALHO, Katia C.; MARCONDES, Rodrigo R.; SOARES JR., Jose Maria; BARACAT, Edmund C.In this work we have evaluated the gene expression profile of prolactin and prolactin receptor in the pituitary and the uterus of female mice with metoclopramide-induced hyperprolactinemia treated with estrogen and/or progesterone. For this purpose, 49 Swiss female mice were allocated to seven groups. Interventions: 50-day treatment with metoclopramide, progesterone and estrogen. Our results showed that in the pituitary, metoclopramide-induced hyperprolactinemia increased prolactin expression. In the castrated animals, progesterone, with or without estrogen, produced an increase in prolactin. Pituitary prolactin receptor and the estrogen and progesterone treatment were responsible for the rise in PRLR-S2. In the uterus, no differences in prolactin expression were found between the different study groups. PRLR-S1 had its expression reduced in all castrated animals as against the castrated group treated with vehicle. In the noncastrated animals, PRLR-52 rose in the metoclopramide-treated group, and, in the castrated animals, its expression diminished in all groups in relation to the vehicle-treated castrated controls. An increase in PRLR-S3 was found in the oophorectomized animals treated with a combination of estrogen and progesterone. PRLR-L rose in the oophorectomized animals treated with progesterone in isolation or in association with estrogen. These findings suggest that metoclopramide associated to progesterone or estrogen may determine an increase in pituitary prolactin and PRLR-S2 expression. The estrogen-progesterone may enhance the expression of PRLR-S3 and PRLR-L isoform of prolactin receptor.
- The progesterone and estrogen modify the uterine prolactin and prolactin receptor expression of hyperprolactinemic mice(2015) AMARAL, Vinicius Cestari do; CARVALHO, Katia Candido; MACIEL, Gustavo Arantes Rosa; SIMONCINI, Tommaso; SILVA, Priscilla Ludovico da; MARCONDES, Rodrigo Rodrigues; SOARES JR., Jose Maria; BARACAT, Edmund ChadaThe aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the prolactin (PRL) and PRL receptor's expression in the uterus of mice. For this purpose, 49 Swiss mice were divided into the following groups: GrSS (non-ovariectomized mice given vehicle); GrMET (non-ovariectomized mice treated with metoclopramide); OvSS (ovariectomized mice given vehicle); OvMET (ovariectomized mice treated with metoclopramide); OvMET+17 beta E (ovariectomized mice treated with metoclopramide and 17 beta estradiol); OvMET+MP (ovariectomized mice treated with metoclopramide and micronized progesterone); OvMET+17 beta E+MP (ovariectomized mice treated with metoclopramide and a solution of 17 beta estradiol and micronized progesterone). Immunohistochemical analyzes were evaluated semi-quantitatively. Our results showed that GrMET, OvMET+MP, and OvMET+17 beta E+MP presented strong PRL expression. OvMET and OvMET+17 beta E presented mild reaction, while GrSS and OvSS presented weak reaction. Concerning PRL receptor, OvMET+MP and OvMET+17 beta E+MP showed strong reaction; GrMET, OvSS, and OvMET+17 beta E showed mild reaction; and GrSS and OvMET showed weak reaction. These findings suggest that progesterone alone or in combination with estrogen may increase the expression of uterine PRL and PRL receptor.
- Hypothalamic transcriptional expression of the kis-speptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes(2017) MARCONDES, Rodrigo Rodrigues; CARVALHO, Katia Candido; GIANNOCCO, Gisele; DUARTE, Daniele Coelho; GARCIA, Natalia; SOARES-JUNIOR, Jose Maria; SILVA, Ismael Dale Cotrim Guerreiro da; MALIQUEO, Manuel; BARACAT, Edmund Chada; MACIEL, Gustavo Arantes RosaOBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n= 10) or estradiol benzoate (0.5 mg) (n= 10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n= 10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-b and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-a genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone-and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosteroneand estradiol-induced polycystic ovary syndrome rats.
bookPart Aspectos moleculares da síndrome dos ovários policísticos(2014) MACIEL, Gustavo Arantes Rosa; BARACAT, Maria Cândida Pinheiro; MARCONDES, Rodrigo Rodrigues; JúNIOR, José Maria Soares; BARACAT, Edmund Chada- Impaired branched-chain amino acid metabolism may underlie the nonalcoholic fatty liver disease-like pathology of neonatal testosterone-treated female rats(2017) ANZAI, Alvaro; MARCONDES, Rodrigo R.; GONCALVES, Thiago H.; CARVALHO, Katia C.; SIMOES, Manuel J.; GARCIA, Natalia; SOARES JR., Jose M.; PADMANABHAN, Vasantha; BARACAT, Edmund C.; SILVA, Ismael D. C. G. da; MACIEL, Gustavo A. R.Polycystic ovary syndrome (PCOS) is frequently associated with non-alcoholic fatty liver disease (NAFLD), but the mechanisms involved in the development of NAFLD in PCOS are not well known. We investigated histological changes and metabolomic profile in the liver of rat models of PCOS phenotype induced by testosterone or estradiol. Two-day old female rats received sc injections of 1.25 mg testosterone propionate (Testos; n = 10), 0.5 mg estradiol benzoate (E2; n = 10), or vehicle (control group, CNT; n = 10). Animals were euthanized at 90-94 d of age and the liver was harvested for histological and metabolomic analyses. Findings showed only Testos group exhibited fatty liver morphology and higher levels of ketogenic and branched-chain amino acids (BCAA). Enrichment analysis showed effects of testosterone on BCAA degradation pathway and mitochondrial enzymes related to BCAA metabolism. Testos group also had a decreased liver fatty acid elongase 2 (ELOVL2) activity. E2 group had reduced lipid and acylcarnitine metabolites in the liver. Both groups had increased organic cation transporters (SLC22A4 and SLC16A9) activity. These findings indicate that neonatal testosterone treatment, but not estradiol, produces histological changes in female rat liver that mimic NAFLD with testosterone-treated rats showing impaired BCAA metabolism and dysfunctions in ELOVL2, SLC22A4 and SLC16A9 activity.
- Histomorphometric analysis of the effects of creatine on rat myometrium(2012) AMARAL, Vinicius Cestari Do; SIMOES, Manuel De Jesus; MARCONDES, Rodrigo Rodrigues; CUBAS, Jairo Jose Matozinho; BARACAT, Edmund Chada; SOARES JR., Jose MariaObjective: To analyze the myometrial thickness of rats subjected to creatine (Cr) ingestion. Study design: A total of 14 rats was equally divided into the control group (ConGr) receiving 1 ml potable water and the creatine group (CrGr) subjected to the ingestion of 1.6 g/kg Cr diluted in 1 ml potable water. At the end of 8 weeks, the animals were anesthetized (xylazine and ketamine) and sacrificed, the uteri and ovaries stained with hematoxylin and eosin, the thickness of both the myometrium and the epithelium measured and the follicles counted. Results: Analysis revealed a significant increase in thickness of the myometrium in the CrGr (272.26 +/- 66.71 mu m) contrasted with that from the ConGr (160.76 +/- 35.65 mu m), CrGr > ConGr (p < 0001). Conclusion: Our data suggest that Cr changed myometrial morphology in rats by enhancing myometrial thickness, but its action mechanism in the smooth muscle is still unclear.
- Exercise Exercise differentially affects metabolic functions and white adipose tissue in female letrozole-and dihydrotestosterone-induced mouse models of polycystic ovary syndrome(2017) MARCONDES, Rodrigo R.; MALIQUEO, Manuel; FORNES, Romina; BENRICK, Anna; HU, Min; IVARSSON, Niklas; CARLSTROM, Mattias; CUSHMAN, Samuel W.; STENKULA, Karin G.; MACIEL, Gustavo A. R.; STENER-VICTORIN, ElisabetHere we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat. In both models, exercise decreased fat mass and inguinal and mesenteric adipose tissue expression of Notch pathway genes, and restored altered mesenteric adipocytes morphology. In conclusion, exercise restored mesenteric adipocytes morphology in DHT- and LET-exposed mice, and insulin sensitivity and mesenteric expression of lipolysis-related genes in LET-exposed mice. Benefits could be explained by downregulation of Notch, and modulation of browning and lipolysis pathways in the adipose tissue.
- Nutritional and dietary aspects in polycystic ovary syndrome: insights into the biology of nutritional interventions(2020) NEVES, Luisa Pinheiro Pimenta; MARCONDES, Rodrigo Rodrigues; MAFFAZIOLI, Giovana De Nardo; SIMOES, Ricardo Santos; MACIEL, Gustavo Arantes Rosa; JR, Jose Maria Soares; BARACAT, Edmund ChadaPolycystic Ovary Syndrome (PCOS) is a complex endocrine disorder, which affects 5-17% of reproductive age women and is often associated with obesity and metabolic impairment. Common treatment strategies are based on exercise, diet and nutrient supplementation since PCOS is often linked with obesity and metabolic impairment. Studies have recommended that nutrition is a key factor in the health maintenance of women with PCOS, however, little is known about the subject in the context of such a disease. This narrative review aims to identify dietary and nutritional aspects of PCOS and discuss the role of nutrients in management of polycystic ovary syndrome in view of clinical trials.
- Acupuncture does not ameliorate metabolic disturbances in the P450 aromatase inhibitor-induced rat model of polycystic ovary syndrome(2017) MALIQUEO, Manuel; BENRICK, Anna; MARCONDES, Rodrigo Rodrigues; JOHANSSON, Julia; SUN, Miao; STENER-VICTORIN, ElisabetNew Findings What is the central question of this study? The effectiveness of low-frequency electroacupuncture in the treatment of metabolic disorders associated with polycystic ovary syndrome (PCOS), an endocrine-metabolic disorder characterized by an imbalance in sex steroid production, is controversial. What is the main finding and its importance? In a rat model of PCOS induced by the inhibition of P450 aromatase, low-frequency electroacupuncture increased low-density lipoprotein-cholesterol but did not improve the insulin resistance or the adipose tissue dysfunction, suggesting that a balance of sex steroids is needed to restore the metabolic function in this rat model of PCOS. Low-frequency electroacupuncture restores sex steroid synthesis and sympathetic activity in women with polycystic ovary syndrome, which may ameliorate its metabolic disturbances, probably by modulating sympathetic nerve activity or sex steroid synthesis. We investigated whether low-frequency electroacupuncture regulates the metabolic function to the same extent as treatment with estradiol or -adrenergic blocking in a rat model of polycystic ovary syndrome induced by a P450 aromatase inhibitor (letrozole). Letrozole (200gday(-1)) or placebo pellets were implanted in prepubertal Wistar rats. Six weeks thereafter, rats were treated for 5-6weeks with the following: low-frequency electroacupuncture (5days per week); a -adrenergic blocker (propranolol hydrochloride, 0.1mgkg(-1), 5days per week); or 17-estradiol (2.0g) every fourth day. Body weight development, body composition, locomotor activity, insulin sensitivity, tissue-specific glucose uptake, lipid profile, adipocyte size, serum concentrations of adiponectin and insulin, and gene expression in inguinal fat were measured. All treatments increased circulating levels of low-density lipoprotein-cholesterol. Estradiol treatment restored locomotor activity and increased insulin sensitivity but did not modify the glucose uptake in muscle and fat. An upregulation of genes related to insulin sensitivity and downregulation of genes related to adipogenesis were observed in subcutaneous adipose tissue from rats exposed to letrozole. Only estradiol treatment normalized the expression of these genes. In conclusion, low-frequency electroacupuncture increased low-density lipoprotein-cholesterol without affecting insulin sensitivity or adipose tissue function, which could suggest effects on hepatic lipid regulation, probably mediated by the action of estradiol or the -adrenergic pathway.