RODRIGO RODRIGUES MARCONDES
Projetos de Pesquisa
Unidades Organizacionais
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
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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.
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- 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.
- Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture(2017) BENRICK, Anna; KOKOSAR, Milana; HU, Min; LARSSON, Martin; MALIQUEO, Manuel; MARCONDES, Rodrigo Rodrigues; SOLIGO, Marzia; PROTTO, Virginia; JERLHAG, Elisabet; SAZONOVA, Antonina; BEHRE, Carl Johan; HOJLUND, Kurt; THOREN, Peter; STENER-VICTORIN, ElisabetA single bout of low-frequency electroacupuncture (EA) causing muscle contractions increases whole-body glucose uptake in insulin-resistant rats. We explored the underlying mechanism of this finding and whether it can be translated into clinical settings. Changes in glucose infusion rate (GIR) were measured by euglycemic-hyperinsulinemic clamp during and after 45 min of low-frequency EA in 21 overweight/obese women with polycystic ovary syndrome (PCOS) and 21 controls matched for age, weight, and body mass index (experiment 1) and in rats receiving autonomic receptor blockers (experiment 2). GIR was higher after EA in controls and women with PCOS. Plasma serotonin levels and homovanillic acid, markers of vagal activity, decreased in both controls and patients with PCOS. Adipose tissue expression of pro-nerve growth factor (proNGF) decreased, and the mature NGF/proNGF ratio increased after EA in PCOS, but not in controls, suggesting increased sympathetic-driven adipose tissue metabolism. Administration of alpha-/beta-adrenergic receptor blockers in rats blocked the increase in GIR in response to EA. Muscarinic and dopamine receptor antagonist also blocked the response but with slower onset. In conclusion, a single bout of EA increases whole-body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.
conferenceObject Transcriptional Expression of Genes Related to Histone Modification in the Hypothalamus of Female Rats Submitted to Neonatal Exposure to Sex Steroids(2014) MARCONDES, Rodrigo Rodrigues; CARVALHO, Katia Candido; GARCIA, Natalia; DUARTE, Daniele Coelho; SOARES JR., Jose Maria; COSTA, Leonardo Tomiatti; AMARAL, Vinicius Cestari; GIANNOCCO, Gisele; BARACAT, Edmund Chada; MACIEL, Gustavo Arantes R.