RESUMO
Acetaminophen (ACE; paracetamol) is one of the most widely used nonsteroidal anti-inflammatory drugs worldwide and is often found in aquatic systems, where it can act on nontarget species and impair fish reproduction. This study aimed to investigate the effects of chronic exposure to environmentally relevant ACE concentrations (0.5, 5 and 50 µg/L) on multiple reproductive parameters in zebrafish (Danio rerio). Gametogenesis was analyzed using histology, morphometry, cell proliferation, and apoptosis. This study also evaluated sex steroids, and prostaglandin E2 (PGE2) levels, gene expression for sex steroids and PGE2 receptors, fertilization rate, and semen quality. In females, exposure to 5 and 50 µg/L ACE induced larger and more abundant vitellogenic follicles and increased follicular atresia. In these treatments, males showed a lower proportion and proliferation of undifferentiated spermatogonia and a higher proportion of TUNEL-positive differentiated spermatogonia, spermatids, and spermatozoa, resulting in lower sperm production. ACE increased 17ß-estradiol (E2) and reduced 11-ketotestosterone levels in the testis, whereas only E2 increased in the ovaries. In both sexes, gonadal PGE2 levels were reduced. ACE at 50 µg/L induced an increase in the gene expression of androgen, estrogen, and PGE2 receptors in the ovaries, and reduced expression in the testes. Results also showed lower egg production and fertilization rate from 28 days of exposure with reduced sperm quality. These results demonstrated that ACE impairs the reproductive performance of zebrafish, affecting multiple reproductive parameters, which may be caused by the synergistic action of the imbalance of sex steroids, with a reduction of PGE2 and its receptors.
Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Feminino , Masculino , Peixe-Zebra/metabolismo , Acetaminofen/metabolismo , Análise do Sêmen , Atresia Folicular , Sêmen , Gametogênese , Estradiol/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Hormônios Esteroides Gonadais/farmacologia , Reprodução , Fertilidade , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismoRESUMO
La pandemia de coronavirus-2 (SARS-CoV-2) relacionada con el SARS 2019-2020 ha traído desafíos sin precedentes a los sectores de la salud en todo el mundo. Hasta noviembre de 2020, ha habido más de 64 millones de casos confirmados y se acercan a 2 millones de muertes en todo el mundo. A pesar de la gran cantidad de casos positivos, existen muy pocos estándares establecidos de atención y opciones terapéuticas disponibles. Hasta la fecha, (Diciembre 2020) todavía no existe una vacuna aprobada por la Administración de Alimentos y Medicamentos (FDA) para COVID-19, aunque existen varias ensayos clínicos en diferentes. etapas de desarrollo. En este documento, hemos realizado una revisión global que evalúa los roles de la edad y el sexo en las hospitalizaciones por COVID-19, las admisiones a la UCI, las muertes en hospitales y las muertes en hogares de ancianos. Hemos identificado una tendencia en la que las personas mayores y los pacientes masculinos se ven afectados significativamente por los resultados adversos.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Hormônios Esteroides Gonadais/farmacologia , Terapia de Reposição Hormonal , SARS-CoV-2 , COVID-19/mortalidade , Estrogênios , Papel de Gênero , COVID-19/tratamento farmacológicoRESUMO
Dehydroepiandrosterone (DHEA) is a steroid hormone secreted by the adrenal glands, gonads and brain. It is a precursor to sex hormones and also is known to have immune modulatory activity. However, little is known about the relationship between DHEA and neutrophils and thus our study evaluates the influence of DHEA in the effector functions of neutrophils. Human neutrophils were treated in vitro with DHEA and further infected with Salmonella enterica serovar Typhimurium. The treatment of neutrophils with 0.01 µM of DHEA increased the phagocytosis of Salmonella independent of TLR4 as the treatment did not modulate the TLR4 expression. Additionally, DHEA caused a decrease in ROS (reactive oxygen species) production and did not influence the formation of the neutrophil extracellular trap (NET). Steroid treated neutrophils, infected or stimulated with LPS (lipopolysaccharide), showed reduced production of IL-8, compared to untreated cells. Also, the protein levels of p-NFκB were decreased in neutrophils treated with DHEA, and this reduction could explain the reduced levels of IL-8. These results led us to conclude that the steroid hormone DHEA has important modulatory functions in neutrophils
Assuntos
Humanos , Masculino , Adulto , Técnicas In Vitro , Desidroepiandrosterona/análise , Neutrófilos/metabolismo , Fagocitose/genética , Hormônios Esteroides Gonadais/farmacologia , Glândulas Suprarrenais/metabolismo , Salmonella enterica/classificaçãoRESUMO
To test the hypothesis that postnatal sexual steroids induce an impairment of domestic male cat reproductive function, this study describes the physical, endocrine, steroidogenical and histological effects of a single, high dose of a postnatal sexual steroid in this species. Twenty male kittens were randomly assigned within the first 24â¯h of birth to: Testosterone enanthate 12.5â¯mg sc (TE; nâ¯=â¯8), medroxyprogesterone acetate 10â¯mg sc (MA; nâ¯=â¯6), or Placebo sc (PL; nâ¯=â¯6). The cats were followed until puberty when they were castrated. Kittens achieved puberty without age differences among groups (Pâ¯>â¯0.05). Two MA cats presented abnormal testicular descent. Histological evaluation of the MA (Pâ¯<â¯0.01), but not of TE testes revealed decreased diameter (Pâ¯<â¯0.01) and epithelial height (Pâ¯<â¯0.01) of the seminiferous tubules. Leydig cell nuclear area was also reduced in this group. Conversely, tubular/intertubular ratio was increased in TE animals (Pâ¯<â¯0.01). Quantitative real-time PCR analysis of mRNA expression of testicular tissue revealed no significant differences among groups for StAR, CYP17A1 and androgen receptors. TE animals showed decreased CYP19A1 mRNA expression (Pâ¯<â¯0.05). In the first 4 postnatal weeks, fecal testosterone (T) values were high, basal and intermediate in TE, MA and PL (Pâ¯<â¯0.05), respectively. These differences progressively diminished and the three groups presented basal T concentrations from the 7th week on (Pâ¯>â¯0.05). It was concluded that the postnatal progestagen initially suppressed the gonadal axis and caused an impairment of spermatogenesis and testicular descent at puberty. Androgen treatment caused downregulation of the final steroidogenic cascade.
Assuntos
Disruptores Endócrinos/farmacologia , Reprodução/efeitos dos fármacos , Esteroides/farmacologia , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Testosterona/análogos & derivados , Animais , Animais Recém-Nascidos , Constituição Corporal/efeitos dos fármacos , Gatos , Anticoncepção/métodos , Anticoncepção/veterinária , Hormônios Esteroides Gonadais/farmacologia , Masculino , Reprodução/fisiologia , Maturidade Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testosterona/farmacologiaRESUMO
NEW FINDINGS: What is the central question of this study? Is there sexual dimorphism in the occurrence of hepatic endoplasmic reticulum stress? What is the main finding and its importance? The transition from prepubertal to the adult age is associated with an increase in the unfolded protein response markers in the liver of male rats, which is probably due to an increase in serum testosterone levels. ABSTRACT: Male rodents present a higher predisposition to obesity and insulin resistance than females. These disorders have been associated with endoplasmic reticulum (ER) stress. To investigate a possible sexual dimorphism in the hepatic occurrence of ER stress, we evaluated the expression of ER stress markers in the livers of male and female rats in two phases of sexual development. In the first experimental model, male and female prepubertal and adult Wistar rats were used. Adult males presented higher body mass and greater mass of the adipose tissue and liver than adult females. Prepubertal animals presented no differences in these parameters between males and females. Despite this finding, the hepatic expression levels of Bip, Ire1α and Xbp1s mRNA were lower in prepubertal males than in females, while in adult animals, they did not differ between sexes. In the second experimental model, we anticipated the sexually mature phase by daily injections of testosterone propionate for 10 days in prepubertal males or by daily injections of oestradiol benzoate for 7 days in prepubertal females. Oestradiol administration in prepubertal females did not change any of the parameters evaluated. Testosterone administration to prepubertal males led to a higher body mass and greater expression of Bip, Ire1α, Atf4 and Xbp1s in the liver. These findings suggest that the increased ER stress predisposition observed in males during puberty is due to an increase in testosterone levels, indicating that ER stress is sexually dimorphic before puberty due to the lack of testosterone in males.
Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/fisiologia , Hormônios Esteroides Gonadais/farmacologia , Fígado/metabolismo , Animais , Endorribonucleases/metabolismo , Estradiol/farmacologia , Feminino , Glucose/metabolismo , Proteínas de Choque Térmico/metabolismo , Fígado/efeitos dos fármacos , Masculino , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Ratos Wistar , Caracteres Sexuais , Maturidade Sexual , Testosterona/farmacologia , Proteína 1 de Ligação a X-Box/metabolismoRESUMO
Among sex steroid hormones, progesterone and estradiol have a wide diversity of physiological activities that target the nervous system. Not only are they carried by the blood stream, but also they are locally synthesized in the brain and for this reason, estradiol and progesterone are considered 'neurosteroids'. The physiological actions of both hormones range from brain development and neurotransmission to aging, illustrating the importance of a deep understanding of their mechanisms of action. In this review, we summarize key roles that estradiol and progesterone play in the brain. As numerous reports have confirmed a substantial neuroprotective role for estradiol in models of neurodegenerative disease, we focus this review on traumatic brain injury and stroke models. We describe updated data from receptor and signaling events triggered by both hormones, with an emphasis on the mechanisms that have been reported as 'rapid' or 'cytoplasmic actions'. Data showing the therapeutic effects of the hormones, used alone or in combination, are also summarized, with a focus on rodent models of middle cerebral artery occlusion (MCAO). Finally, we draw attention to evidence that neuroprotection by both hormones might be due to a combination of 'cytoplasmic' and 'nuclear' signaling.
Assuntos
Isquemia Encefálica , Encéfalo/efeitos dos fármacos , Hormônios Esteroides Gonadais/farmacologia , Fármacos Neuroprotetores/farmacologia , Animais , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/prevenção & controle , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Isquemia Encefálica/prevenção & controle , Modelos Animais de Doenças , Estradiol/farmacologia , Humanos , Modelos Teóricos , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/prevenção & controle , Neuroproteção/efeitos dos fármacos , Progesterona/farmacologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
In this work, we describe the participation of the adenylate cyclase/3'-5'-cyclic adenonsine monophosphate (cAMP) pathway in the seasonal follicular secretion of progesterone (P4 ) and testosterone (T), and its relationship with the maturation of Rhinella arenarum oocytes. Under gonadotropin stimulation, P4 secretion was the dominant steroid produced during the reproductive period, resulting in 100% germinal vesicle breakdown (GVBD) in oocytes in vitro; in contrast, T and estradiol (E2 ) secretion increased (â¼16 nM/20 follicles and â¼80 pM/20 follicles, respectively) during the non-reproductive period, but only yielded 50% GVBD. Treatment of the follicles with dibutyryl-cAMP or forskolin induced a significant increase in T secretion during both periods, but P4 secretion did not significantly change and GVBD did not occur. These results suggest that high cAMP levels in the oocyte maintain meiotic arrest and prevent the induction effect of follicular steroids. An increase in cAMP levels in denuded oocytes, however, negatively regulated T-induced maturation since treatment with increasing db-cAMP or forskolin inhibited their maturation. Therefore, we hypothesize that an elevation in T during the non-reproductive period favors its aromatization to E2 , leading to follicle growth. During the reproductive period, P4 production might promote oocyte maturation when environmental conditions are favorable for reproduction. Together, the results indicate that steroidogenesis is seasonal and depends on gonadotropic activity in R. arenarum.
Assuntos
AMP Cíclico/farmacologia , Hormônios Esteroides Gonadais/biossíntese , Hormônios Esteroides Gonadais/fisiologia , Oogênese , Animais , Bufo arenarum , Células Cultivadas , Colforsina/farmacologia , AMP Cíclico/metabolismo , Feminino , Líquido Folicular/química , Líquido Folicular/metabolismo , Hormônios Esteroides Gonadais/farmacologia , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Oogênese/efeitos dos fármacos , Oogênese/fisiologia , Folículo Ovariano/química , Folículo Ovariano/metabolismo , Progesterona/biossíntese , Progesterona/farmacologia , Progesterona/fisiologia , Testosterona/biossíntese , Testosterona/farmacologia , Testosterona/fisiologiaRESUMO
Testosterone (TES), other androgens and female sex steroids induce non-genomic rapid relaxing effects in airway smooth muscle (ASM). In guinea pig ASM, basal tension was relaxed by dehydroepiandrosterone (DHEA) and TES; 17ß-estradiol (E2) had a small effect. Blockers of L-type voltage dependent Ca2+ channel (L-VDCC, D-600) and store operated Ca2+ channel (SOC, 2-APB) also relaxed the basal tone. In tracheal myocytes, DHEA and TES diminished intracellular basal Ca2+ concentrations (b[Ca2+]i) as D-600+2-APB but to a higher extend. TES after D-600+2APB or Pyr3, a blocker of canonical transient receptor potential 3 (TRPC3), further decreased b[Ca2+]i rendering this response equal to TES alone. With indomethacin, the b[Ca2+]i decrease induced by the blockade of L-VDCC and TRPC3 was not changed by the addition of TES. PGE2 or forskolin addition after D600+2-APB, decreased b[Ca2+]i resembling TES response. An adenylate cyclase inhibitor followed by D-600+2-APB lowered b[Ca2+]i, TES showed no further effect. Carbachol-induced [Ca2+]i increment was reduced by TES or DHEA. 17ß-estradiol diminished KCl-induced contraction and, in tracheal myocytes, the voltage-dependent inward Ca2+ current. CONCLUSION: DHEA and TES diminish ASM tone and b[Ca2+]i by blocking L-VDCC and probably a constitutively active TRPC3, and by PGE2 synthesis. E2 lowers ASM basal tone by blocking only L-VDCC.
Assuntos
Canais de Cálcio Tipo L/metabolismo , Cálcio/metabolismo , Hormônios Esteroides Gonadais/farmacologia , Espaço Intracelular/metabolismo , Músculo Liso/fisiologia , Traqueia/fisiologia , Animais , Compostos de Boro/farmacologia , Carbacol/farmacologia , AMP Cíclico/metabolismo , Desidroepiandrosterona/farmacologia , Estradiol/farmacologia , Galopamil/farmacologia , Cobaias , Masculino , Células Musculares/efeitos dos fármacos , Células Musculares/metabolismo , Músculo Liso/efeitos dos fármacos , Prostaglandinas/metabolismo , Canais de Cátion TRPC/metabolismo , Testosterona/farmacologiaRESUMO
The aim of this study was to evaluate the amount of non- and sulfated glycosaminoglycans in the ovariectomized mice uterus, after treatment with ovarian steroids. For this purpose, 50 adult female mice were divided into five groups with 10 animals/each: control group: CG (ovary intact), and ovariectomized groups: OG (vehicle), EG (estradiol), PG (progesterone) and EPG (estradiol combined to progesterone). The treatments started 30 days after ovariectomy. All the animals were treated for 50 consecutive days. These hormones were administered in a sterile oily solution via gavage. Twenty-four hours after the last treatment, all animals were euthanized, removing the uterine horn for biochemical analyses. To quantify, the hyaluronic acid (HA) used ELISA-like fluorometric assay, and the sulfated glycosaminoglycans (GAGs) used agarose gel electrophoresis. The amount of HA was significantly higher in the group treated with progesterone (PG) compared to the others groups (p < 0.05), and in the group treated with estradiol (EG), the amount of chondroitin/dermatan sulfate was significantly higher compared to the others groups (p < 0.05), and in the group treated with progesterone (PG), the amount of heparan sulfate was significantly lower compared to the others groups, except to control group (p < 0.05). Our results showed that the estroprogestative therapy after long time (50 days) profoundly affected the amount of glycosaminoglycans in uterine. These changes may be indicative of uterine pathology such as the development of tumor.
Assuntos
Estradiol/farmacologia , Glicosaminoglicanos/metabolismo , Hormônios Esteroides Gonadais/farmacologia , Progesterona/farmacologia , Útero/metabolismo , Animais , Estradiol/administração & dosagem , Feminino , Hormônios Esteroides Gonadais/administração & dosagem , Camundongos , Ovariectomia , Progesterona/administração & dosagem , Útero/efeitos dos fármacosRESUMO
Sex steroids can determine several responses in the clinical evolution of malaria. Seventy Balb-c mice were randomly distributed into 7 groups (10 mice per group): G1 to G6 corresponding to castrated females, castrated females that received estradiol cypionate, uncastrated females, castrated males, castrated males that received intramuscular testosterone decanoate and uncastrated males infected with Plasmodium berghei, and G7, the control group. The mice were evaluated with regard to survival, parasitemia, temperature, body weight, hemoglobin level (anemia) and splenic index. Castrated infected females had lower rates of survival. In the castrated male, the administration of testosterone had a negative influence on survival. There was a progressive increase in parasitemia without repercussions for survival. Castration had a significant influence on weight gain in females. Weight loss was observed in all mice, except those in groups G2 and G5, although this bore no direct relation to parasitemia. A significant and progressive decline in temperature and hemoglobin levels occurred in mice over the course of their infection, which differed from the G7 group. The weight of the spleen in relation to total body weight did not differ among the groups of infected mice, but was significantly higher than it was for the control group.
Assuntos
Estradiol/análogos & derivados , Malária/parasitologia , Plasmodium berghei/fisiologia , Testosterona/análogos & derivados , Animais , Peso Corporal/efeitos dos fármacos , Estradiol/farmacologia , Feminino , Hormônios Esteroides Gonadais/farmacologia , Hemoglobinas/metabolismo , Malária/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Orquiectomia , Ovariectomia , Parasitemia/parasitologia , Parasitemia/patologia , Distribuição Aleatória , Baço/efeitos dos fármacos , Baço/patologia , Esplenomegalia , Testosterona/farmacologiaRESUMO
In this work we showed the relationship between seasonal periods and the response of R. arenarum follicles and oocytes to different steroids. Using in vitro germinal vesicle breakdown (GVBD) assays, we demonstrated that P4 is the main steroid capable of inducing maturation in R. arenarum oocytes and follicles. In the second part of this work we showed that androgens can activate pre-maturation promoting factors (pre-MPFs) such as P4, by cytoplasm microinjection experiments. The results indicated that the steroids assayed induced oocyte and follicle maturation in a dose- and time-dependent manner. In oocytes, P4 was the most efficient steroid as a maturation inducer (EC50 of the reproductive period, 6 nM, EC50 of the non-reproductive period â 30 nM). Androgens (DHEA, dehydroepiandrosterone; T, testosterone; and AD, androstenedione) were less efficient maturation inducers than P4 (EC50 reproductive period â 50, 120 and 600 nM respectively). Similar results were obtained with intact follicles in both seasonal periods. Although the response of follicles to the different androgens was variable, in no case was it above the above the response induced by P4. Independently of the season, oocytes and follicles incubated in P4, P5 and T underwent GVBD after 6-10 h while oocytes and follicles incubated in DHEA and AD matured more slowly. Furthermore, we demonstrated that microinjection of mature cytoplasm from androgen-treated oocytes is sufficient to promote GVBD in immature recipient oocytes (DHEA, 57 ± 12%; AD, 60 ± 8%; T, 56 ± 13%). Thus, androgens such as DHEA, T and AD are as competent as P4 to activate pre-MPF.
Assuntos
Hormônios Esteroides Gonadais/farmacologia , Fator Promotor de Maturação/metabolismo , Meiose/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Precursores de Proteínas/metabolismo , Androgênios/administração & dosagem , Androgênios/farmacologia , Animais , Bufo arenarum , Células Cultivadas , Citoplasma/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Feminino , Hormônios Esteroides Gonadais/administração & dosagem , Técnicas de Maturação in Vitro de Oócitos/métodos , Microinjeções , Oócitos/citologia , Oócitos/fisiologia , Oogênese/efeitos dos fármacos , Folículo Ovariano/citologia , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologia , Progesterona/administração & dosagem , Progesterona/farmacologia , Estações do Ano , Testosterona/administração & dosagem , Testosterona/farmacologia , Fatores de TempoRESUMO
BACKGROUND: There is growing interest in sex differences and RAS components. However, whether gender influences cardiac angiotensin I-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity is still unknown. In the present work, we determined the relationship between ACE and ACE2 activity, left ventricular function and gender in spontaneously hypertensive rats (SHRs). METHODOLOGY/PRINCIPAL FINDINGS: Twelve-week-old female (F) and male (M) SHRs were divided into 2 experimental groups (n = 7 in each group): sham (S) and gonadectomized (G). Fifty days after gonadectomy, we measured positive and negative first derivatives (dP/dt maximum left ventricle (LV) and dP/dt minimum LV, respectively), hypertrophy (morphometric analysis) and ACE and ACE2 catalytic activity (fluorimetrically). Expression of calcium handling proteins was measured by western blot. Male rats exhibited higher cardiac ACE and ACE2 activity as well as hypertrophy compared to female rats. Orchiectomy decreased the activity of these enzymes and hypertrophy, while ovariectomy increased hypertrophy and ACE2, but did not change ACE activity. For cardiac function, the male sham group had a lower +dP/dt than the female sham group. After gonadectomy, the +dP/dt increased in males and reduced in females. The male sham group had a lower -dP/dt than the female group. After gonadectomy, the -dP/dt increased in the male and decreased in the female groups when compared to the sham group. No difference was observed among the groups in SERCA2a protein expression. Gonadectomy increased protein expression of PLB (phospholamban) and the PLB to SERCA2a ratio in female rats, but did not change in male rats. CONCLUSION: Ovariectomy leads to increased cardiac hypertrophy, ACE2 activity, PLB expression and PLB to SERCA2a ratio, and worsening of hemodynamic variables, whereas in males the removal of testosterone has the opposite effects on RAS components.
Assuntos
Cardiomegalia/enzimologia , Cardiomegalia/fisiopatologia , Hormônios Esteroides Gonadais/farmacologia , Hipertensão/enzimologia , Contração Miocárdica/efeitos dos fármacos , Peptidil Dipeptidase A/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , Pressão Sanguínea/efeitos dos fármacos , Western Blotting , Peso Corporal/efeitos dos fármacos , Cardiomegalia/complicações , Densitometria , Feminino , Gônadas/efeitos dos fármacos , Gônadas/cirurgia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos Endogâmicos SHR , Sístole/efeitos dos fármacosRESUMO
Mast cells (MCs) are versatile effector and regulatory cells in various physiologic, immunologic, and pathologic processes. In addition to the well-characterized IgE/FcεRI-mediated degranulation, a variety of biological substances can induce MCs activation and release of their granule content. Sex steroids, mainly estradiol and progesterone, have been demonstrated to elicit MCs activation. Most published studies have been conducted on MCs lines or freshly isolated peritoneal and bone marrow-derived MC without addressing gender impact on MC response. Our goal was to investigate if the effect of estradiol, progesterone, testosterone, and dihydrotestosterone (DHT) on MCs may differ depending on whether female or male rats are used as MCs donors. Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation. In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used. In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids.
Assuntos
Hormônios Esteroides Gonadais/farmacologia , Liberação de Histamina/efeitos dos fármacos , Mastócitos/imunologia , Peritônio/citologia , Receptores de IgE/biossíntese , Animais , Degranulação Celular/imunologia , Células Cultivadas , Di-Hidrotestosterona/farmacologia , Estradiol/farmacologia , Feminino , Imunoglobulina E/imunologia , Masculino , Mastócitos/citologia , Progesterona/farmacologia , Ratos , Ratos Sprague-Dawley , Fatores Sexuais , Substância P/metabolismo , Testosterona/farmacologiaRESUMO
Sex steroid hormones are important players in the control of sex differentiation by regulating gonadal development in teleosts. Although estrogens are clearly associated with the ovarian differentiation in teleosts, the effects of androgens on early gonadal development are still a matter of debate. Traditionally, 11-ketotestosterone (11-KT) is considered the major androgen in fish; however, 5α-dihydrotestosterone (5α-DHT), the most potent androgen in tetrapods, was recently found in fish testis and plasma, but its physiological role is still unknown. In this context, the expression of genes associated with steroidogenesis and spermatogenesis, body growth and sex differentiation were assessed in Odontesthes bonariensis larvae fed with food supplemented with two doses of 5α-DHT (0.1 and 10µg/g of food) from hatching to 6weeks of age. At the lowest dose, 5α-DHT treated larvae showed an estrogenic gene expression pattern, with low hsd11b2 and high cyp19a1a and er2 expression levels with no differences in sex ratio. At the highest dose, 5α-DHT produced a male-shifted sex ratio and the larvae exhibited a gene expression profile characteristic of an advancement of spermatogenesis, with inhibition of amh and stimulation of ndrg3. No differences were observed in somatic growth. These results suggest that in this species, 5α-DHT could have a role on sex differentiation and its effects can differ according to the dose.
Assuntos
Di-Hidrotestosterona/farmacologia , Processos de Determinação Sexual/genética , Smegmamorpha/genética , Espermatogênese/genética , Animais , Aromatase/genética , Di-Hidrotestosterona/metabolismo , Feminino , Proteínas de Peixes/genética , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hormônios Esteroides Gonadais/farmacologia , Hormônios Esteroides Gonadais/fisiologia , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Masculino , Diferenciação Sexual/genética , Razão de Masculinidade , Smegmamorpha/crescimento & desenvolvimentoRESUMO
AIMS: Previous studies have shown that brain opioid peptides exert an inhibitory influence on gonadotropin secretion. Different types of brain opioids, such as ß-endorphin, enkephalin, and dynorphin, exert their actions by binding to specific opioid receptors (i.e., µ, δ, and κ, respectively). The present study determined the effects of chronic treatment with morphine in female rats with pharmacologically induced estrus on behavior and opioid receptor gene and protein expression in the hypothalamus, striatum, and periaqueductal gray. MAIN METHODS: Female ovariectomized rats treated with estrogen+progesterone received 3.5mg/kg morphine once per day for 6days. We evaluated general activity, sexual behavior, Oprm1, Oprd1, and Oprk1 gene expression, and µ opioid receptor (MOR), δ opioid receptor (DOR), and κ opioid receptor (KOR) protein expression in the hypothalamus, striatum, and periaqueductal gray in adult virgin female ovariectomized rats. KEY FINDINGS: Chronic morphine treatment increased locomotion and grooming behavior, decreased immobility time, decreased sexual behavior, and decreased the lordosis quotient. The molecular biology results showed that morphine treatment increased Oprm1 gene and MOR protein expression in the striatum and decreased KOR protein expression in the hypothalamus in animals that were assessed for general activity. The animals that were evaluated for sexual behavior exhibited an increase in Oprm1 expression in the periaqueductal gray and increase in KOR expression in the striatum. SIGNIFICANCE: These results suggest that both opioid system activation and sex hormones alter behavioral and molecular patterns in ovariectomized rats within a relatively short period of time.
Assuntos
Analgésicos Opioides/farmacologia , Hormônios Esteroides Gonadais/farmacologia , Morfina/farmacologia , Receptores Opioides/metabolismo , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Estrogênios/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Ovariectomia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Substância Cinzenta Periaquedutal/metabolismo , Progesterona/farmacologia , Ratos , Ratos WistarRESUMO
The medial nucleus of the amygdala (MeA) is a complex component of the "extended amygdala" in rats. Its posterodorsal subnucleus (MePD) has a remarkable expression of gonadal hormone receptors, is sexually dimorphic or affected by sex steroids, and modulates various social behaviors. Dendritic spines show remarkable changes relevant for synaptic strength and plasticity. Adult males have more spines than females, the density of dendritic spines changes in the course of hours to a few days and is lower in proestrous and estrous phases of the ovarian cycle, or is affected by both sex steroid withdrawal and hormonal replacement therapy in the MePD. Males also have more thin spines than mushroom-like or stubby/wide ones. The presence of dendritic fillopodia and axonal protrusions in the MePD neuropil of adult animals reinforces the evidence for local plasticity. Estrogen affects synaptic and cellular growth and neuroprotection in the MeA by regulating the activity of the cyclic AMP response element-binding protein (CREB)-related gene products, brain-derived neurotrophic factor (BDNF), the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) and the activity-regulated cytoskeleton-related protein (Arc). These effects on signal transduction cascades can also lead to local protein synthesis and/or rearrangement of the cytoskeleton and subsequent numerical/morphological alterations in dendritic spines. Various working hypotheses are raised from these experimental data and reveal the MePD as a relevant region to study the effects of sex steroids in the rat brain.
Assuntos
Tonsila do Cerebelo/patologia , Espinhas Dendríticas/patologia , Hormônios Esteroides Gonadais/farmacologia , Neurônios/patologia , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Biomarcadores/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proliferação de Células/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas do Citoesqueleto/metabolismo , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/ultraestrutura , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/ultraestrutura , Ciclo Estral , Feminino , Masculino , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurópilo/efeitos dos fármacos , Neurópilo/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Fatores Sexuais , Transdução de SinaisRESUMO
We have recently demonstrated that gonadal steroid hormones decrease formalin-induced temporomandibular joint nociception in rats. Given that the attenuation of inflammation is a potential mechanism underlying this antinociceptive effect, we evaluated the effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation. Plasma extravasation, a major sign of acute inflammation, and neutrophil migration, an important event related to tissue injury, were evaluated. Formalin induced significantly lower temporomandibular joint plasma extravasation and neutrophil migration in proestrus females than in males and in diestrus females. Since estradiol serum level is high in proestrus females and low in diestrus females and in males, these findings suggest that the high physiological level of estradiol decreases temporomandibular joint inflammation. Estradiol but not progesterone administration in ovariectomized females significantly decreased formalin-induced plasma extravasation and neutrophil migration, an effect that was blocked by the estrogen receptor antagonist ICI 182780. Plasma extravasation and neutrophil migration were not affected by orchiectomy, but testosterone or estradiol administration in orchidectomized males significantly decreased them. The androgen receptor antagonist flutamide blocked the anti-inflammatory effect of testosterone while ICI 182780 blocked that of estradiol in males. Previous intravenous administration of a nonspecific selectin inhibitor significantly decreased formalin-induced temporomandibular joint nociception and neutrophil migration in males, revealing a potent and positive correlation between temporomandibular joint nociception and inflammation. Taken together, these findings demonstrate a pronounced anti-inflammatory effect of estradiol and testosterone in the temporomandibular joint region and suggest that this effect may mediate, at least in part, the antinociceptive effect of these hormones.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Artrite/tratamento farmacológico , Artrite/patologia , Hormônios Esteroides Gonadais/farmacologia , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Transtornos da Articulação Temporomandibular/patologia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite/metabolismo , Modelos Animais de Doenças , Feminino , Hormônios Esteroides Gonadais/uso terapêutico , Masculino , Ratos , Ratos Wistar , Transtornos da Articulação Temporomandibular/metabolismo , Resultado do TratamentoRESUMO
Cell morphology and its interaction with the extracellular environment are integrated processes involving a number of intracellular controllers orchestrating cytoskeletal proteins and their interaction with the cell membrane and anchorage proteins. Sex steroids are effective regulators of cell morphology and tissue organisation, and recent evidence indicates that this is obtained through the regulation of the actin cytoskeleton. Intriguingly, many of these regulatory actions related to cell morphology are achieved through the rapid, nonclassical signalling of sex steroid receptors to kinase cascades, independently from nuclear alteration of gene expression or protein synthesis. The identification of the mechanistic basis for these rapid actions on cell cytoskeleton has special relevance for the characterisation of the effects of sex steroids under physiological conditions, such as for the development of neurone/neurone interconnections and dendritic spine density. This is considered to be critical for gender-specific differences in brain function and dysfunction. Recent advancements in the characterisation of the molecular basis of the extranuclear signalling of sex steroids help to clarify the role of oestrogen and progesterone in the brain, and may turn out to be of relevance for clinical purposes. This review highlights the regulatory effects of oestrogens and progesterone on actin cytoskeleton and neurone morphology, as well as recent progresses in the characterisation of these mechanisms, providing insights and working hypotheses on possible clinical applications for the modulation of these pathways in the central nervous system.
Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Espinhas Dendríticas/efeitos dos fármacos , Hormônios Esteroides Gonadais/farmacologia , Neurônios/efeitos dos fármacos , AnimaisRESUMO
We evaluated the in vitro effects of estradiol, progesterone, and testosterone on the molting process, which is the initial and crucial step in the development of the muscular larvae (ML or L1) to adult worm. Testosterone had no significative effect on the molting rate of the parasite, however, progesterone decreased the molting rate about a 50% in a concentration- and time-independent pattern, while estradiol had a slight effect (10%). The gene expression of caveolin-1, a specific gene used as a marker of parasite development, showed that progesterone and estradiol downregulated its expression, while protein expression was unaffected. By using flow citometry, a possible protein that is recognized by a commercial antiprogesterone receptor antibody was detected. These findings may have strong implications in the host-parasite coevolution, in the sex-associated susceptibility to this infection and could point out to possibilities to use antihormones to inhibit parasite development.