RESUMO
OBJECTIVES: Ischaemia and reperfusion-induced microvascular dysfunction is a serious problem encountered during a variety surgical procedures, leading to systemic inflammation and affecting remote organs, specially the lungs. 17ß-Oestradiol reduces pulmonary repercussions from various acute lung injury forms. Here, we focused on the 17ß-oestradiol therapeutic effects after aortic ischaemia and reperfusion (I/R) by evaluating lung inflammation. METHODS: Twenty-four Wistar rats were submitted to I/R by insufflation of a 2-F catheter in thoracic aorta for 20 min. Reperfusion took 4 h and 17ß-oestradiol (280 µg/kg, i.v.) was administered after 1 h of reperfusion. Sham-operated rats were controls. Bronchoalveolar lavage was performed and lung samples were prepared for histopathological analysis and tissue culture (explant). Interleukin (IL)-1ß, IL-10 and tumour necrosis factor-α were quantified. RESULTS: After I/R, higher number of leukocytes in bronchoalveolar lavage were reduced by 17ß-oestradiol. The treatment also decreased leukocytes in lung tissue. I/R increased lung myeloperoxidase expression, with reduction by 17ß-oestradiol. Serum cytokine-induced neutrophil chemoattractant 1 and IL-1ß increased after I/R and 17ß-oestradiol decreased cytokine-induced neutrophil chemoattractant 1. I/R increased IL-1ß and IL-10 in lung explants, reduced by 17ß-oestradiol. CONCLUSIONS: Our results showed that 17ß-oestradiol treatment performed in the period of reperfusion, modulated the systemic response and the lung repercussions of I/R by thoracic aortic occlusion. Thus, we can suggest that 17ß-oestradiol might be a supplementary approach leading the lung deterioration after aortic clamping in surgical procedures.
Assuntos
Lesão Pulmonar , Traumatismo por Reperfusão , Ratos , Masculino , Animais , Estradiol/farmacologia , Estradiol/uso terapêutico , Estradiol/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Ratos Wistar , Interleucina-10/uso terapêutico , Aorta Torácica/patologia , Pulmão/patologia , Isquemia , Citocinas/metabolismo , Fatores Quimiotáticos/metabolismo , Fatores Quimiotáticos/uso terapêutico , Síndrome de Resposta Inflamatória SistêmicaRESUMO
Oestrogens treatment is often used to induce oestrus behaviour in anoestrous mares to aid in the collection of stallion semen and as recipient mares to receive embryos when combined with progesterone. However, there are no studies to describe the effect of dose and individual mare on the intensity and duration of the response, in both anoestrous and cyclic mares. In Experiment 1, 13 anoestrous mares were treated with one of five doses of oestradiol benzoate (OB) (1, 1.5, 2, 3 and 4 mg) per mare in five consecutive treatment periods (n = 65), to determine the response in terms of endometrial oedema and oestrous behaviour. Experiment 2 and 3 used 3 mg of OB in cyclic mares to confirm or deny the presence of an active corpus luteum (CL). There was a dose rate of OB and individual mare effect (p < 0.05) on the intensity and persistence of endometrial oedema and oestrous behaviour. A total of 2 mg OB was enough to induce endometrial oedema and oestrous behaviour within 48 h in most mares. Mares with an active CL did not show endometrial oedema following treatment of 3 mg OB.
RESUMO
A protocol to induce lactation was applied to non-pregnant gilts. In Experiment I, five gilts with oestrus synchronized through oral supplementation of 20 mg altrenogest for 18 days received: 10 mg oestradiol cypionate (EC) on the last day of oestrous expression (D0); 10 mg EC and 300 mg long-acting progesterone (P4) on D26; and two 0.53 mg doses of a prostaglandin F2α analogue (PGF) 12 h apart on D36. Blood was collected on D12, D19, D26 and D33. Milk secretion started in all gilts 24 h after PGF administration and lasted at least 8 days. Milk samples were collected from D37 to D45. The serum P4 concentration was lower on D12 than subsequently (p < .05), but the oestradiol concentration was unaltered (p > .05). The milk produced during the induced lactation was generally richer in protein and poorer in fat compared to the milk from the lactation of a reference sow. In Experiment II, the same protocol induced lactation in two gilts, which nursed fostered piglets for 22 days. Thus, lactation was induced in all treated gilts and the milk produced was capable to nurture fostered piglets.
Assuntos
Lactação , Progesterona , Animais , Suínos , Feminino , Sus scrofa/metabolismo , Estro , LeiteRESUMO
The effect of three different hormonal protocols to prepare anestrous recipient mares on embryo survival was evaluated. The first group consisted of only progesterone administration (NE) 4 days before embryo transfer, while the recipients from the other two groups received a single administration of 2.5 mg of oestradiol benzoate (SE) 2 days earlier or 8 mg of oestradiol split in increasing doses for 5 consecutive days (LE) ending 3 days before progesterone treatment. The likelihood of recovering an embryo 2 days after transfer was 46.1% (6/13), 62.5% (5/8) and 85.7% (6/7) for recipient mares from the no oestrus, short and long oestrous groups respectively (p = .09). In conclusion, the presence and duration of oestradiol treatment before progesterone administration tended to influence the embryo survival in anestrous recipients 2 days after transfer. The surviving embryos recovered from the three different groups of recipients did not show any difference in size and morphology.
Assuntos
Estradiol , Progesterona , Cavalos , Feminino , Animais , Progesterona/farmacologia , Progesterona/uso terapêutico , Estradiol/farmacologia , Transferência Embrionária/veterinária , Desenvolvimento EmbrionárioRESUMO
OBJECTIVES: The surgical treatment for diseases of the descending aorta is related to a high mortality rate because of the activation of a systemic inflammatory process due to ischaemia and reperfusion (I/R) injury. Activation of coagulation can contribute to the inflammatory process, resulting in microcirculatory damage and multiple organ failure. Our goal was to evaluate the role of prophylactic intravenous 17ß-oestradiol (E2) in coagulation, the inflammatory response and hepatic injury after occlusion of the descendent proximal aorta in male rats. METHODS: Wistar male rats were randomized and allocated to 3 groups (n = 8 per group): sham, surgically manipulated; IR, animals subjected to I/R; and E2, animals treated with E2 (280 µg/kg, intravenously) before I/R. I/R was induced by insertion of a 2-Fr Fogarty arterial embolectomy catheter in the descending aorta, which was occluded for 20 min, followed by a reperfusion period of 2 h. Serological markers, platelet aggregation, hepatic vascular flow, systemic and liver inflammatory response and apoptosis were analysed. The coagulation process was evaluated by thromboelastometry. RESULTS: The aortic occlusion led to a reduction in plasma fibrinogen concentration in parallel with increased clotting time, greater clot firmness and reduced lysis. E2 treatment was able to increase fibrinogen, prevent the increase in clotting time and normalize clot firmness, but it exerted only a mild effect on clot lysis. Platelet aggregation was increased by IR, and E2 treatment was able to reduce it. There was a reduction in flow percentage in the IR group that was not prevented by E2. In parallel, higher aggregate formation was observed in the vessels of the IR group of animals. There was increased systemic release of interleukin-1-ß, interleukin-6 and interleukin-10 in the IR group, which was reduced in the treated animals. CONCLUSIONS: The current results suggest that pretreatment with E2 before an ischaemic period induced by occlusion of the proximal descending aorta is effective in preventing alterations in coagulation and systemic inflammation due to I/R injury.
Assuntos
Aorta Torácica , Traumatismo por Reperfusão , Animais , Aorta Torácica/cirurgia , Estradiol/farmacologia , Estradiol/uso terapêutico , Humanos , Inflamação/prevenção & controle , Masculino , Microcirculação , Ratos , Ratos Wistar , Traumatismo por Reperfusão/prevenção & controleRESUMO
O maior entrave para o êxito de um programa de transferência de embrião (TE) está relacionado às receptoras, tanto a qualidade de características reprodutivas, quanto a sincronização entre doadoras e receptoras. Éguas doadoras, geralmente, apresentam melhor escore corporal e disponibilidade alimentar nos períodos de seca, fazendo com que iniciem o seu ciclo estral precocemente enquanto éguas receptoras se encontram ainda em anestro ou período transicional, o que dificulta a TE. Vários estudos foram realizados com o objetivo de utilizar receptoras acíclicas como receptoras de embrião. Assim, podem ser utilizadas nos programas de TE quando submetidas a protocolos hormonais que mimetizam o ciclo estral natural. Uma diversidade de protocolos é encontrada na literatura, usando diferentes doses, posologias e intervalos do uso de estradiol associado a progestágenos. Portanto, objetivou-se analisar resultados de pesquisas com protocolos hormonais que poderiam ajudar a solucionar a escassez de receptoras cíclicas e maximizar os resultados da biotécnica de transferência de embriões.(AU)
There are obstacles to the success of equine embryo transfer programs, concomitantly there has been an increase in the popularity of the technique. One of the most urgent issues to overcome is related to the recipient mare availability and the donor-recipient synchrony. Usually, the donor mares have a higher body condition score and are fed a higher quality diet than recipient mares during the non-breeding season. Therefore, the donor mares start cycling earlier than recipient mares, which makes embryo transfer challenging. Several studies have been carried on finding hormonal protocols that mimic the natural oestrous cycle to allow the use of noncycling recipient mares for embryo transfer programs. Many protocols can be found in the literature, using different doses and intervals. Among the main difference is the use of progestogens, which can be used alone or in combination with oestradiol. The aim of this review was to analyse results that could help solve the lack of recipient mares and improve the results of the embryo transfer technique.(AU)
Assuntos
Animais , Feminino , Transferência Embrionária/métodos , Cavalos/embriologia , Progestinas , EstradiolRESUMO
Integrating ecophysiological and behavioural discoveries in conservation and management plans is essential to preserve scarce and elusive species such as the European wildcat (Felis silvestris). The purpose of this study was to characterize the monthly variation in the steroid reproductive hormone metabolite levels (oestradiol, progesterone and testosterone) in this species and to test its possible association with a monthly pattern of faecal marking. By collecting fresh faecal samples in Montes do Invernadeiro Natural Park (Galicia, Northwest Spain) each month, we obtained a total of 110 samples belonging to 25 different individuals. We conducted enzyme immunoassays which allowed us to track the annual variation in reproductive hormone excretion patterns in wildcat scats. Furthermore, we also evaluated the possible relation between the faeces used as marks and the reproductive hormone levels. We found that oestradiol and progesterone metabolite levels exhibited a distinct pattern, both increasing during the breeding months. Oestradiol metabolite larger peaks were found during March and April, whereas the highest concentration of progesterone metabolites appeared in July. On the contrary, testosterone metabolite levels did not significantly change depending on the month. Moreover, we did not find any evidence that the faecal marking behaviour pattern was associated with reproductive hormone metabolite levels. It seems that other factors related to habitat and food resources could be more important in the performance of this behaviour.
Assuntos
Comportamento Animal/fisiologia , Fezes/química , Felis/fisiologia , Animais , Estradiol/análise , Feminino , Masculino , Progesterona/análise , Estações do Ano , Espanha , Testosterona/análiseRESUMO
The aim of this study was to evaluate different times for timed artificial insemination (TAI) in buffalo submitted to a P4/E2/eCG-based protocol. In this study, 204 buffaloes were distributed into one of two groups (TAI56, n=103 and TAI64, n=101). At a random stage of the oestrous cycle (Day 0 = D0), in the morning (TAI56, a.m.) or afternoon (TAI64, p.m.), buffaloes received an intravaginal progesterone device (P4; 1.0 g) plus EB (2.0 mg i.m.). On D9 a.m. (TAI56) or p.m. (TAI64), the P4 was removed and buffaloes received PGF2a (0.53 mg i.m. sodium cloprostenol) and eCG (400 IU i.m.). On D10 a.m. (TAI56) or p.m. (TAI64), 24 h after P4 removal, buffaloes were treated with EB (1.0 mg i.m.). Buffaloes from TAI56 and TAI64 were inseminated 56 and 64 h after P4 removal (D11, p.m. and D12, a.m., respectively). Ultrasound examinations were performed on D0 to ascertain ovarian follicular status, at TAI to measure the diameter of the dominant follicle (DF) and D42 for pregnancy diagnosis. The statistical analysis was performed using the GLIMMIX procedure of SAS®. There was no difference between TAI56 and TAI64 for the diameter of the DF at TAI and the pregnancy per TAI. It was concluded that TAI 56 or 64 h after P4 removal did not affect fertility in buffaloes submitted to the induction of ovulation with EB. The present research supports that is possible to perform TAI at any time throughout the day in buffalo synchronized during the non-breeding season.(AU)
O objetivo deste estudo foi avaliar diferentes momentos para a realização da IATF em búfalas submetidas a um protocolo à base de P4/E2/eCG. Neste estudo, 204 búfalas foram distribuídas em um de dois grupos (IATF56, n=103 e IATF64, n=101). Em estágio aleatório do ciclo estral (Dia 0 = D0), pela manhã (IATF56, manhã) ou pela tarde (IATF64, tarde), as búfalas receberam um dispositivo intravaginal de progesterona (P4; 1,0 g) e BE (2,0 mg i.m.). No D9 pela manhã (IATF56) ou pela tarde (IATF64), a P4 foi removida e as búfalas receberam PGF2a (0,53 mg i.m. cloprostenol sódico) e eCG (400 UI i.m.). No D10 pela manhã (IATF56) ou pela tarde (IATF64), 24 h após a remoção da P4, as búfalas foram tratadas com BE (1,0 mg i.m.). As búfalas dos grupos IATF56 e IATF64 foram inseminadas 56 e 64 h após a remoção da P4 (D11, pela tarde e D12, pela manhã, respectivamente). Avaliações ultrassonográficas foram realizadas no D0 para verificar o status folicular ovariano, na IATF para medir o diâmetro do folículo dominante (FD) e no D42 para o diagnóstico de gestação. A análise estatística foi realizada utilizando o procedimento GLIMMIX do SAS®. Não houve diferença entre os grupos IATF56 e IATF64 no diâmetro do FD na IATF e na prenhez por IATF. Conclui-se que a IATF 56 ou 64 h após a remoção da P4 não afeta a fertilidade de búfalas submetidas à indução da ovulação com BE. A presente pesquisa evidencia que é possível realizar a IATF durante todo o dia em búfalas sincronizadas durante a estação reprodutiva desfavorável.(AU)
Assuntos
Animais , Feminino , Inseminação Artificial/métodos , Inseminação Artificial/veterinária , Guias como Assunto , Benzoatos , Anestro , Búfalos , Folículo Ovariano , Indução da OvulaçãoRESUMO
ABSTRACT: The aim of this study was to evaluate different times for timed artificial insemination (TAI) in buffalo submitted to a P4/E2/eCG-based protocol. In this study, 204 buffaloes were distributed into one of two groups (TAI56, n=103 and TAI64, n=101). At a random stage of the oestrous cycle (Day 0 = D0), in the morning (TAI56, a.m.) or afternoon (TAI64, p.m.), buffaloes received an intravaginal progesterone device (P4; 1.0 g) plus EB (2.0 mg i.m.). On D9 a.m. (TAI56) or p.m. (TAI64), the P4 was removed and buffaloes received PGF2a (0.53 mg i.m. sodium cloprostenol) and eCG (400 IU i.m.). On D10 a.m. (TAI56) or p.m. (TAI64), 24 h after P4 removal, buffaloes were treated with EB (1.0 mg i.m.). Buffaloes from TAI56 and TAI64 were inseminated 56 and 64 h after P4 removal (D11, p.m. and D12, a.m., respectively). Ultrasound examinations were performed on D0 to ascertain ovarian follicular status, at TAI to measure the diameter of the dominant follicle (DF) and D42 for pregnancy diagnosis. The statistical analysis was performed using the GLIMMIX procedure of SAS®. There was no difference between TAI56 and TAI64 for the diameter of the DF at TAI and the pregnancy per TAI. It was concluded that TAI 56 or 64 h after P4 removal did not affect fertility in buffaloes submitted to the induction of ovulation with EB. The present research supports that is possible to perform TAI at any time throughout the day in buffalo synchronized during the non-breeding season.
RESUMO: O objetivo deste estudo foi avaliar diferentes momentos para a realização da IATF em búfalas submetidas a um protocolo à base de P4/E2/eCG. Neste estudo, 204 búfalas foram distribuídas em um de dois grupos (IATF56, n=103 e IATF64, n=101). Em estágio aleatório do ciclo estral (Dia 0 = D0), pela manhã (IATF56, manhã) ou pela tarde (IATF64, tarde), as búfalas receberam um dispositivo intravaginal de progesterona (P4; 1,0 g) e BE (2,0 mg i.m.). No D9 pela manhã (IATF56) ou pela tarde (IATF64), a P4 foi removida e as búfalas receberam PGF2a (0,53 mg i.m. cloprostenol sódico) e eCG (400 UI i.m.). No D10 pela manhã (IATF56) ou pela tarde (IATF64), 24 h após a remoção da P4, as búfalas foram tratadas com BE (1,0 mg i.m.). As búfalas dos grupos IATF56 e IATF64 foram inseminadas 56 e 64 h após a remoção da P4 (D11, pela tarde e D12, pela manhã, respectivamente). Avaliações ultrassonográficas foram realizadas no D0 para verificar o status folicular ovariano, na IATF para medir o diâmetro do folículo dominante (FD) e no D42 para o diagnóstico de gestação. A análise estatística foi realizada utilizando o procedimento GLIMMIX do SAS®. Não houve diferença entre os grupos IATF56 e IATF64 no diâmetro do FD na IATF e na prenhez por IATF. Conclui-se que a IATF 56 ou 64 h após a remoção da P4 não afeta a fertilidade de búfalas submetidas à indução da ovulação com BE. A presente pesquisa evidencia que é possível realizar a IATF durante todo o dia em búfalas sincronizadas durante a estação reprodutiva desfavorável.
RESUMO
An injection of unesterified oestradiol (E2 ) facilitates receptive behaviour in E2 benzoate (EB)-primed, ovariectomised female rats when it is administered i.c.v. or systemically. The present study tested the hypothesis that inhibitors of protein kinase A (PKA), protein kinase G (PKG) or the Src/mitogen-activated protein kinase (MAPK) complex interfere with E2 facilitation of receptive behaviour. In Experiment 1, lordosis induced by i.c.v. infusion of E2 was significantly reduced by i.c.v. administration of Rp-cAMPS, a PKA inhibitor, KT5823, a PKG inhibitor, and PP2 and PD98059, Src and MAPK inhibitors, respectively, between 30 and 240 minutes after infusion. In Experiment 2, we determined whether the ventromedial hypothalamus (VMH) is one of the neural sites at which those intracellular pathways participate in lordosis behaviour induced by E2 . Administration of each of the four protein kinase inhibitors into the VMH blocked facilitation of lordosis induced by infusion of E2 also into the VMH. These data support the hypothesis that activation of several protein kinase pathways is involved in the facilitation of lordosis by E2 in EB-primed rats.
Assuntos
Antagonistas de Estrogênios/farmacologia , Lordose/fisiopatologia , Inibidores de Proteínas Quinases/farmacologia , Núcleo Hipotalâmico Ventromedial/fisiologia , Animais , Carbazóis/farmacologia , AMP Cíclico/análogos & derivados , AMP Cíclico/farmacologia , Estradiol/fisiologia , Feminino , Flavonoides/farmacologia , Infusões Intraventriculares , Lordose/induzido quimicamente , Masculino , Microinjeções , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/farmacologia , Ratos , Tionucleotídeos/farmacologia , Núcleo Hipotalâmico Ventromedial/efeitos dos fármacosRESUMO
NEW FINDINGS: What is the central question of this study? Can Na+ depletion mobilize Na+ from the skin reservoir in ovariectomized rats? Does oestrogen replacement change the amount and the dynamics of skin Na+ storage? Is the reduced salt appetite after Na+ depletion in ovariectomized rats with oestrogen replacement related to changes in the skin Na+ ? What is the main finding and its importance? This work demonstrated that acute body Na+ depletion induced by frusemide mobilized the osmotically inactive skin Na+ reservoir to become osmotically active. Oestrogen treatment decreased the induced Na+ intake in ovariectomized rats but did not modulate the inactive Na+ reservoir in control conditions or its mobilization induced by Na+ depletion. ABSTRACT: Oestradiol, which is an important hormone for water and electrolyte balance, also has a role in the inhibition of induced Na+ appetite. Sodium can be stored in the skin in osmotically active or inactive forms, and this skin Na+ reservoir may be involved in the control of body Na+ levels during physiopathological challenges. In this study, we investigated whether the effect of sodium depletion by frusemide can mobilize Na+ from the skin reservoir and whether oestradiol replacement changes or mobilizes the Na+ reserves in the skin. Ovariectomized Wistar rats were treated with vehicle or oestradiol for 7 days to evaluate the effects of oestrogen on the hydroelectrolyte balance, intake responses and skin Na+ and water content in basal conditions. Furthermore, the effects of oestrogen were evaluated after 24 h frusemide-induced whole-body Na+ depletion. Oestradiol-replaced rats exhibited reduced water intake without any significant changes in salt intake, Na+ excretion or water and Na+ skin content in basal conditions. After sodium depletion, both vehicle- and oestradiol-treated rats exhibited an increase in the osmotically active skin Na+ , which was associated with a decrease of the inactive skin Na+ reservoir. Oestrogen decreased the hypertonic saline intake induced by Na+ depletion, but it was not associated with any significant changes in the skin Na+ reservoir. Thus, sodium depletion is able to change the inactive-active skin Na+ reservoir balance. However, the oestrogenic modulation of sodium appetite after Na+ depletion is probably not related to the action of this hormone in the skin Na+ reservoir balance.
Assuntos
Estradiol/farmacologia , Hiponatremia/induzido quimicamente , Hiponatremia/metabolismo , Pele/metabolismo , Inibidores de Simportadores de Cloreto de Sódio e Potássio/toxicidade , Sódio/deficiência , Animais , Estradiol/uso terapêutico , Feminino , Furosemida/toxicidade , Hiponatremia/tratamento farmacológico , Ovariectomia/efeitos adversos , Ovariectomia/tendências , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Cloreto de Sódio na Dieta/administração & dosagemRESUMO
This study examined the feasibility of transcervical embryo recovery after the hormonal treatment to induce cervical dilation, following the 7-day oestrous synchronization protocol in multiparous Santa Inês ewes. A total of 23 cyclic ewes received two doses of 37.5 µg of d-cloprostenol by latero-vulvar route 7 days apart. After the second injection of d-cloprostenol, the ewes were checked for oestrus (every 12 hr) and then mated by fertile rams throughout the oestrous period. All ewes received 37.5 µg of d-cloprostenol (latero-vulvar) and 1 mg of oestradiol benzoate by either intramuscular (EBim group; n = 12) or intravaginal (EBivg group; n = 11) route 16 hr before embryo flushing. Twenty minutes before the flushing, 50 IU of oxytocin were administered intravenously. The oestrous response (i.e., the percentage of ewes that showed signs of oestrous behaviour after the second d-cloprostenol injection) was 91.3% (21/23). The proportion of successfully penetrated ewes (81.8% compared with 80.0%), the mean duration of embryo flushing (24.7 ± 2.0 min compared 26.2 ± 1.9 min), the flushing fluid recovery rate (94.8 ± 1.3% compared with 91.0 ± 2.9%) and the average number of structures recovered per ewe (0.5 ± 0.4 compared with 0.8 ± 0.4) did not vary (p > 0.05) between the EBim and EBivg groups. Viable embryos were recovered from 41.2% (7/17) of successfully penetrated ewes. It can be concluded that nonsurgical (i.e., transcervical) embryo collection can be performed in oestrous-synchronized Santa Inês ewes pretreated with d-cloprostenol, oxytocin and oestradiol benzoate, with the latter hormone administered by either the intramuscular or intravaginal route.
Assuntos
Cloprostenol/farmacologia , Transferência Embrionária/veterinária , Estradiol/análogos & derivados , Ocitocina/farmacologia , Carneiro Doméstico , Animais , Transferência Embrionária/métodos , Embrião de Mamíferos , Estradiol/farmacologia , Sincronização do Estro , Feminino , Primeira Fase do Trabalho de Parto/efeitos dos fármacos , Masculino , Gravidez , Coleta de Tecidos e Órgãos/veterináriaRESUMO
Leydig-cell tumours (LCTs) are rare endocrine tumours of the testicular interstitium, with recent increased incidence. Symptoms include precocious puberty in children; and erectile dysfunction, infertility and/or gynaecomastia, in adults. So far, scientific evidence points to aromatase (CYP19) overexpression and excessive oestrogen and insulin-like growth factor (IGF) -1 production as responsible for Leydig-cell tumourigenesis. LCTs are usually benign; however, malignant LCTs respond poorly to chemo/radiotherapy, highlighting the need to identify novel targets for treatment. Herein, we investigated the potential role of the histamine receptor H4 (HRH4) as a therapeutic target for LCTs using R2C rat Leydig tumour cells, a well-documented in vitro model for Leydigioma. Also, we studied for the first time the expression of CYP19, IGF-1R, oestrogen receptor (ER) α, ERß, androgen receptor (AR) and HRH4 in human prepubertal LCTs versus normal prepubertal testes (NPTs). HRH4 agonist treatment inhibited steroidogenesis and proliferation in R2C cells and also negatively affected their pro-angiogenic capacity in vitro and in vivo, as assessed by evaluating the proliferative activity of human umbilical vein endothelial cells and by means of the quail chorioallantoic membrane assay, respectively. Moreover, E2 and IGF-1 inhibited HRH4 mRNA and protein levels. In human prepubertal LCTs, CYP19, IGF-1R, ERα and ERß were overexpressed compared with NPTs. In contrast, HRH4 staining was weak in LCTs, but moderate/strong and confined to the interstitium in NPTs. Importantly, HRH4 was absent or barely detectable in seminiferous tubules or germ cells. Overall, our results point to HRH4 as a novel therapeutic target in LCTs.
Assuntos
Antineoplásicos/farmacologia , Guanidinas/farmacologia , Agonistas dos Receptores Histamínicos/farmacologia , Imidazóis/farmacologia , Tumor de Células de Leydig/tratamento farmacológico , Receptores Histamínicos H4/agonistas , Neoplasias Testiculares/tratamento farmacológico , Tioureia/análogos & derivados , Fatores Etários , Inibidores da Angiogênese/farmacologia , Animais , Aromatase/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Coturnix/embriologia , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lactente , Tumor de Células de Leydig/metabolismo , Tumor de Células de Leydig/patologia , Masculino , Terapia de Alvo Molecular , Neovascularização Patológica , Ratos , Receptor IGF Tipo 1 , Receptores Androgênicos/metabolismo , Receptores Histamínicos H4/metabolismo , Receptores de Somatomedina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Inibidores da Síntese de Esteroides/farmacologia , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Tioureia/farmacologiaRESUMO
Steroid sex hormones produce physiological effects in reproductive tissues and also in nonreproductive tissues, such as the brain, particularly in cortical, limbic and midbrain areas. Dopamine (DA) neurones involved in processes such as prolactin secretion (tuberoinfundibular system), motor circuit regulation (nigrostriatal system) and driving of motivated behaviour (mesocorticolimbic system) are specially regulated by sex hormones. Indeed, sex hormones promote neurochemical and behavioural effects induced by drugs of abuse by tuning midbrain DA neurones in adult animals. However, the long-term effects induced by neonatal exposure to sex hormones on dopaminergic neurotransmission have not been fully studied. The present study aimed to determine whether a single neonatal exposure with oestradiol valerate (EV) results in a programming of dopaminergic neurotransmission in the nucleus accumbens (NAcc) of adult female rats. To answer this question, electrophysiological, neurochemical, cellular, molecular and behavioural techniques were used. The data show that frequency but not amplitude of the spontaneous excitatory postsynaptic current is significantly increased in NAcc medium spiny neurones of EV-treated rats. In addition, DA content and release are both increased in the NAcc of EV-treated rats, caused by an increased synthesis of this neurotransmitter. These results are functionally associated with a higher percentage of EV-treated rats conditioned to morphine, a drug of abuse, compared to controls. In conclusion, neonatal programming with oestradiol increases NAcc dopaminergic neurotransmission in adulthood, which may be associated with increased reinforcing effects of drugs of abuse.
Assuntos
Condicionamento Operante/efeitos dos fármacos , Dopamina/metabolismo , Estradiol/farmacologia , Morfina/farmacologia , Neurônios/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Analgésicos Opioides/farmacologia , Animais , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Estrogênios/farmacologia , Feminino , Neurônios/metabolismo , Núcleo Accumbens/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
The effects of intrauterine exposure to 17ß-oestradiol (E2) are well studied for the male prostate and there are accumulating evidences that the exposure to high dosages leads to a hypomorphic development. However, there is a lack of information about the effects of intrauterine exposure to E2 in the prostate of rodent females, and such research becomes relevant in view of the presence of functional prostate in a proportion of women, and the morphophysiological similarities between the prostate of female rodents and the prostate of women. This study uses histochemical, immunohistochemical, immunofluorescence and three-dimensional (3D) reconstruction techniques to evaluate the effects of intrauterine exposure to E2 (500 BW/d) on neonatal prostate development in both male and female gerbils. It was verified that intrauterine exposure to E2 promotes epithelial proliferation and growth of prostatic budding in females, whereas in males the prostatic budding shows hypomorphic growth in the VMP (Ventral Mesenchymal Pad) as well as reduced epithelial proliferation. Together, the data demonstrate that intrauterine exposure to E2 causes different effects on male and female prostates of the gerbil even at the early postnatal development of the gland.
Assuntos
Estradiol/metabolismo , Estradiol/farmacologia , Próstata/efeitos dos fármacos , Animais , Animais Recém-Nascidos/embriologia , Animais Recém-Nascidos/metabolismo , Disruptores Endócrinos/metabolismo , Disruptores Endócrinos/farmacologia , Feminino , Gerbillinae/embriologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Próstata/embriologia , Receptores Androgênicos/efeitos dos fármacos , Receptores de Estrogênio/efeitos dos fármacos , Fatores SexuaisRESUMO
INTRODUCTION: Physical capabilities are an important parameter of the functional development of adolescents, not only by chronological age but also by their maturational state, as individuals with the same chronological age can have different performance to their less mature counterparts. OBJECTIVE: To compare and relate the physical capabilities and hormonal markers according to sex and maturity of adolescents. METHODS: The sample consisted of adolescents of both sexes, aged 10 to 14 years. We evaluated the maturity achieved by a predictive equation of skeletal age, physical capabilities (explosive power of upper and lower limbs, velocity of upper limbs and agility) and hormonal markers (testosterone and oestradiol) via chemiluminescence. RESULTS: Females showed more advanced maturational status, higher weight, body height and oestradiol levels; males performed better in the explosive force of upper and lower limbs, upper limb speed, agility and testosterone levels. In the normal maturational state males showed greater skeletal age, body weight, body height, explosive strength of upper and lower limbs, and testosterone levels; the females in the normal maturational state had higher skeletal age, body weight, body height, explosive upper limb strength and oestradiol levels. In the male correlation analysis, skeletal age was related to the explosive strength of upper and lower limbs and testosterone; while skeletal age in females was related to explosive upper limb strength and oestradiol. CONCLUSION: It is concluded that maturation, testosterone and oestradiol levels play an important role in the physical aspects and performance of motor skills of adolescents, especially in upper limb force which was more related to the maturation obtained by skeletal age of males and females.
INTRODUÇÃO: A capacidade física é um importante parâmetro do desenvolvimento funcional a ser investigado em crianças e adolescentes, não apenas pela idade cronológica e sim pelo seu estado maturacional, já que sujeitos com mesma idade cronológica podem apresentar desempenho diferente ao seu par menos maturado. OBJETIVO: Comparar e relacionar as capacidades físicas e marcadores hormonais de acordo com o sexo e maturação de crianças e adolescentes. MÉTODO: A amostra foi composta por 89 crianças e adolescentes de ambos os sexos de 10 a 13 anos. Foram avaliados a maturação obtida através de uma equação preditora da idade óssea, capacidades físicas (força explosiva de membros superiores e inferiores, velocidade de membros superiores e agilidade) e marcadores hormonais (testosterona e estradiol) através do método de quimioluminescência RESULTADOS: Na comparação entre os sexos as meninas obtiveram estado maturacional mais avançado, maior peso, estatura corporal e níveis de estradiol; já os meninos apresentaram melhor desempenho na força explosiva de membros superior e inferior, velocidade de membro superior, agilidade e níveis de testosterona. Relativo à maturação, os meninos em estado maturacional normal apresentaram maior idade óssea, peso e estatura corporal, força explosiva de membros superior e inferior, e níveis de testosterona; já as meninas no estado maturacional normal obtiveram maior idade óssea, peso, estatura corporal, força explosiva de membro superior e níveis de estradiol. Na análise de correlação dos meninos a idade óssea se relacionou com a força explosiva de membros superior e inferior e testosterona; já a idade óssea das meninas se relacionou com a força explosiva de membro superior e estradiol. CONCLUSÃO: Desta forma, se conclui que maturação e os níveis de testosterona e estradiol exercem um importante papel nos aspectos físicos e no desempenho das habilidades motoras das crianças e dos adolescentes, principalmente na força de membro superior a qual se mostrou mais relacionada com a maturação obtida pela idade óssea de meninos e meninas.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Testosterona , Constituição Corporal , Criança , Aptidão Física , Adolescente , EstradiolRESUMO
Water deprivation (WD) induces changes in plasma volume and osmolality, which in turn activate several responses, including thirst, the activation of the renin-angiotensin system (RAS) and vasopressin (AVP) and oxytocin (OT) secretion. These systems seem to be influenced by oestradiol, as evidenced by the expression of its receptor in brain areas that control fluid balance. Thus, we investigated the effects of oestradiol treatment on behavioural and neuroendocrine changes of ovariectomized rats in response to WD. We observed that in response to WD, oestradiol treatment attenuated water intake, plasma osmolality and haematocrit but did not change urinary volume or osmolality. Moreover, oestradiol potentiated WD-induced AVP secretion, but did not alter the plasma OT or angiotensin II (Ang II) concentrations. Immunohistochemical data showed that oestradiol potentiated vasopressinergic neuronal activation in the lateral magnocellular PVN (PaLM) and supraoptic (SON) nuclei but did not induce further changes in Fos expression in the median preoptic nucleus (MnPO) or subfornical organ (SFO) or in oxytocinergic neuronal activation in the SON and PVN of WD rats. Regarding mRNA expression, oestradiol increased OT mRNA expression in the SON and PVN under basal conditions and after WD, but did not induce additional changes in the mRNA expression for AVP in the SON or PVN. It also did not affect the mRNA expression of RAS components in the PVN. In conclusion, our results show that oestradiol acts mainly on the vasopressinergic system in response to WD, potentiating vasopressinergic neuronal activation and AVP secretion without altering AVP mRNA expression.
Assuntos
Desidratação/fisiopatologia , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Neurônios/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Supraóptico/efeitos dos fármacos , Desequilíbrio Hidroeletrolítico/prevenção & controle , Animais , Arginina Vasopressina/agonistas , Arginina Vasopressina/análise , Arginina Vasopressina/metabolismo , Comportamento Animal/efeitos dos fármacos , Desidratação/terapia , Ingestão de Líquidos/efeitos dos fármacos , Terapia de Reposição de Estrogênios , Feminino , Hidratação , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Ovariectomia/efeitos adversos , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/patologia , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/metabolismo , Área Pré-Óptica/patologia , Ratos Wistar , Órgão Subfornical/efeitos dos fármacos , Órgão Subfornical/metabolismo , Órgão Subfornical/patologia , Núcleo Supraóptico/metabolismo , Núcleo Supraóptico/patologia , Núcleo Vestibular Lateral/efeitos dos fármacos , Núcleo Vestibular Lateral/metabolismo , Núcleo Vestibular Lateral/patologia , Desequilíbrio Hidroeletrolítico/sangue , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/fisiopatologiaRESUMO
Removing dietary phyto-oestrogens in adult male rats causes obesity and diabetes. As whey proteins have been reported to reduce food intake and improve glucose homoeostasis, we investigated whether they could attenuate susceptibility to obesity and diabetes due to phyto-oestrogen deprivation. To this end, thirty male Wistar rats were fed a high-phyto-oestrogen (HP) or a phyto-oestrogen-free (PF) diet for 10 weeks; six rats from each group were killed. The remaining HP animals (six animals) continued receiving the HP diet for 6 weeks. The remaining PF rats (twelve rats) were divided in two groups: one was given the PF diet and the other a variation of the PF diet plus whey protein (PF-W). Body weight, food intake and adipose tissue weights were recorded. Hypothalamic mRNA expressions of orexigenic (neuropeptide Y, agouti-related protein (AgRP)) and anorexigenic (pro-opiomelanocortin (POMC), cocaine-amphetamine-related transcript (CART)) neuropeptides were quantified by real-time PCR. Serum glucose, insulin and total thyroxine (T4), thyroid-stimulating hormone, testosterone and oestradiol were assessed. After 10 weeks of PF diet, increased body weight, adiposity and energy intake, with up-regulation of AgRP and down-regulation of POMC', were observed. Longer treatment exacerbated these results, increased total T4 levels, reduced oestradiol levels and impaired glucose homoeostasis. PF-W reduced energy intake and increased POMC expression; however, body weight and adiposity remained unchanged. PF-W could not prevent the hormonal changes or the high circulating glucose levels induced by phyto-oestrogen deprivation, but reduced fasting insulin. These data demonstrate that, although 6 weeks of whey administration could not prevent obesity in phyto-oestrogen-deprived rats, the reduction in energy intake and circulating insulin could be beneficial with longer treatments.
Assuntos
Ingestão de Energia/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotálamo/metabolismo , Obesidade , Proteínas do Soro do Leite/farmacologia , Ração Animal/análise , Animais , Glicemia , Dieta , Suplementos Nutricionais , Masculino , Fitoestrógenos/administração & dosagem , Fitoestrógenos/farmacologia , RNA/genética , RNA/metabolismo , Ratos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Oestradiol (E2) acts in the hypothalamus to regulate luteinising hormone (LH) and prolactin (PRL) secretion. Tamoxifen (TX) has been extensively used as a selective oestrogen receptor modulator, although its neuroendocrine effects remain poorly understood. In the present study, we investigated the hypothalamic effects of TX in rats under low or high circulating E2 levels. Ovariectomised (OVX) rats treated with oil, E2 or TX, or E2 plus TX, were evaluated for hormonal secretion and immunohistochemical analyses in hypothalamic areas. Both E2 and TX reduced LH levels, whereas TX blocked the E2 -induced surges of LH and PRL. TX prevented the E2 -induced expression of progesterone receptor (PR) in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC), although it did not alter PR expression in OVX rats. TX blocked the E2 induction of c-Fos in AVPV neurones, consistent with the suppression of LH surge. However, TX failed to prevent E2 inhibition of kisspeptin expression in the ARC. In association with the blockade of PRL surge, TX increased the phosphorylation of tyrosine hydroxylase (TH) in the median eminence of OVX, E2 -treated rats. TX also precluded the E2 -induced increase in TH expression in the ARC. In all immunohistochemical analyses, TX treatment in OVX rats caused no measurable effect on the hypothalamus. Thus, TX is able to prevent the positive- but not negative-feedback effect of E2 on the hypothalamus. TX also blocks the effects of E2 on tuberoinfundibular dopaminergic neurones and PRL secretion. These findings further characterise the anti-oestrogenic actions of TX in the hypothalamus and provide new information on the oestrogenic regulation of LH and PRL.