RESUMO
The pattern of gonadotropin secretion along the estrous cycle was elegantly described in rats. Less information exists about the pattern of gonadotropin secretion in gonad-intact mice, particularly regarding the follicle-stimulating hormone (FSH). Using serial blood collections from the tail-tip of gonad-intact C57BL/6 mice on the first day of cornification (transition from diestrus to estrus; hereafter called proestrus), we observed that the luteinizing hormone (LH) and FSH surge cannot be consistently detected since only one out of eight females (12%) showed increased LH levels. In contrast, a high percentage of mice (15 out of 21 animals; 71%) exhibited LH and FSH surges on the proestrus when a single serum sample was collected. Mice that exhibited LH and FSH surges on the proestrus showed c-Fos expression in gonadotropin-releasing hormone- (GnRH; 83.4% of co-localization) and kisspeptin-expressing neurons (42.3% of co-localization) of the anteroventral periventricular nucleus (AVPV). Noteworthy, mice perfused on proestrus, but that failed to exhibit LH surge, showed a smaller, but significant expression of c-Fos in GnRH (32.7%) and AVPVKisspeptin (14.0%) neurons. Finally, 96 serial blood samples were collected hourly in eight regular cycling C57BL/6 females to describe the pattern of LH and FSH secretion along the estrous cycle. Small elevations in LH and FSH levels were detected at the time expected for the LH surge. In summary, the present study improves our understanding of the pattern of gonadotropin secretion and the activation of central components of the hypothalamic-pituitary-gonadal axis along the estrous cycle of C57BL/6 female mice.
Assuntos
Kisspeptinas , Hormônio Luteinizante , Animais , Ciclo Estral , Feminino , Hormônio Foliculoestimulante , Hormônio Liberador de Gonadotropina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-fos , RatosRESUMO
Aggression is an evolutionary behavior as it has a role in survival, increasing one's access to food, shelter, status and reproduction. Testosterone and Cortisol are hormones often linked to aggressive behavior. We gathered and organized data from the last five years on the relation among Testosterone, Cortisol and aggression, while assessing the methods used by those scientific papers. A systematic review was made according to PRISMA guidelines. The search for indexed articles was performed in January 2019 using the keywords aggress* AND Testosterone AND Cortisol in three databases: Web of Science, SCOPUS and PsycInfo. The specific role of Testosterone and Cortisol in aggressive behavior is not unanimous. However, most articles found either an increase in Testosterone or a decrease in Cortisol associated with this behavior. There is the need for standardizing methods of triggering and assessing aggressive behavior, taking into account the assessment of social desirability and its impacts.
Agressividade é um comportamento evolutivo, tendo um papel na sobrevivência ao aumentar o acesso à comida, abrigo, status social e reprodução. A testosterona e o cortisol são hormônios frequentemente associados a comportamentos agressivos. Este estudo reúne e organiza dados dos últimos cinco anos sobre a relação entre testosterona, cortisol e agressividade, avaliando também os métodos utilizados pelos artigos. Uma revisão sistemática foi conduzida segundo as diretrizes do PRISMA. Uma pesquisa eletrônica de artigos foi realizada em janeiro de 2019, usando as palavras-chave agress* AND Testosterone AND Cortisol em três bancos de dados: Web of Science, SCOPUS e PsycInfo. O papel desses hormônios no comportamento agressivo não é unânime, porém a maioria dos artigos incluídos encontrou um aumento na testosterona ou uma diminuição no cortisol, associados a esse comportamento. Há a necessidade de padronizar os métodos de induzir e de avaliar agressividade, levando em conta a desejabilidade social e seus impactos.
La agresividad es un comportamiento evolutivo, por desempeñar papel en la supervivencia, aumentando el acceso a comida, refugio, estatus social y reproducción. La testosterona y el cortisol son hormonas frecuentemente relacionadas con el comportamiento agresivo. Este estudio reúne y organiza datos de los últimos cinco años sobre la relación entre testosterona, cortisol y agresividad, junto a los métodos de evaluación utilizados por los artículos científicos. Se realizó una revisión sistemática de acuerdo con las directrices PRISMA. La búsqueda electrónica de artículos indexados fue realizada enero de 2019, utilizándose de las palabras clave aggress* AND Testosterone AND Cortisol en tres bases de datos: Web of Science, SCOPUS y PsycInfo. El papel de esas hormonas en el comportamiento agresivo no es unánime, aunque la mayoría de los artículos incluídos hayan hallado aumento de testosterona o disminución en cortisol, asociados a ese comportamiento. Se necesita la estandarización de los métodos de inducción y evaluación de la agresividad, teniendo en cuenta la deseabilidad social y sus impactos.
Assuntos
Humanos , Masculino , Feminino , Adulto , Comportamento , Agressão , Hormônios , Testosterona , Violência , HidrocortisonaRESUMO
SUMMARY: A large body of evidence supports the protective role of the flavonol antioxidant compound quercetin in mammals. We tested the hypothesis that quercetin can protect against the hypothalamus-pituitary-gonadal (HPG) axis defect like a reduction in gonadotropins and testicular hormones and abnormal semen analysis induced by chronic unpredictable stress (CUS), possibly via the downregulation of oxidative stress (ROS) and p53-Bax-caspase-3 pathways. Rats were either exposed to a variety of unpredictable stressors daily before being sacrificed after 3 weeks (model group) or were treated with quercetin (50 mg/kg body weight/day) at the same time the CUS were induced (treated group). Harvested testicular tissues were stained with basic histological staining, and testis homogenates were assayed for the tumor suppressor p53, apoptosis regulator Bax, B-cell lymphoma 2 (Bcl-2), caspase-3, malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, harvested epididymis tissues were used to assess semen analysis, and blood samples were assayed for the testicular hormone testosterone, the adrenal cortex hormone corticosterone, and the anterior pituitary gonadotropins, follicular stimulating hormone (FSH) and luteinizing hormone (LH). CUS induced profound testicular damage and significantly (p<0.05) induced p53, Bax, caspase-3, MDA, and corticosterone, which were significantly (p<0.05) inhibited by quercetin except corticosterone. Whereas, quercetin significantly (p<0.05) increased FSH, LH, testosterone, Bcl-2, GPx, and SOD levels that were inhibited by CUS. In addition, CUS induced oligozoospermia, asthenozoospermia, and teratozoospermia, which were significantly (p<0.05) protected by quercetin. Thus, Quercetin protects against CUS-induced HPG defects in rats, which is associated with the inhibition of ROS-p53-Bax-caspase-3 axis.
RESUMEN: El papel protector del compuesto antioxidante flavonol quercetina en los mamíferos ha sido ampliamente reportado. Probamos la hipótesis que la quercetina puede proteger contra el defecto del eje hipotálamo-hipofisiario- gonadal (HHG) como una reducción de gonadotropinas y hormonas testiculares y análisis de semen anormal inducido por estrés crónico impredecible (ECI), posiblemente a través de la regulación reducida del estrés oxidativo (REO) y las vías p53- Bax-caspasa-3. Las ratas fueron expuestas a una variedad de fac- tores estresantes impredecibles diariamente antes de ser sacrificadas después de 3 semanas (grupo modelo) o fueron tratadas con quercetina (50 mg / kg de peso corporal / día) al mismo tiempo que se indujo la ECI (grupo tratado). Los tejidos testiculares fueron teñidos con tinción histológica básica y los homogeneizados de testículo se analizaron para determinar el supresor de tumores p53, el regulador de apoptosis Bax, el linfoma de células B 2 (Bcl-2), la caspasa-3, el malondialdehído (MDA), la glutatión peroxidasa (GPx) y superóxido dismutasa (SOD). Además, se utilizaron tejidos del epidídimo recolectados para evaluar el análisis de semen y se analizaron muestras de sangre para determinar la hormona testicular testosterona, la hormona corticosterona de la corteza suprarrenal y las gonadotropinas de la hipófisis anterior, la hormona estimulante folicular (FSH) y la hormona luteinizante (LH). El ECI indujo daño testicular importante e indujo significativamente niveles de (p <0,05) p53, Bax, caspasa-3, MDA y corticosterona, que fueron inhibidos (p <0,05) por la quercetina. La quercetina aumentó significativamente (p <0,05) los niveles de FSH, LH, testosterona, Bcl-2, GPx y SOD que fueron inhibidos por ECI. Además, ECI indujo oligozoospermia, astenozoospermia y teratozoospermia, protegidos de manera significativa (p <0,05) por la quercetina. Por lo tanto, la quercetina protege contra los defectos de HHG inducidos por ECI en ratas, lo que está asociado con la inhibición del eje ROS-p53-Bax-caspasa-3.
Assuntos
Animais , Masculino , Ratos , Quercetina/administração & dosagem , Estresse Fisiológico , Doenças Testiculares/etiologia , Testículo/efeitos dos fármacos , Antioxidantes/administração & dosagem , Testículo/lesões , Doença Crônica , Proteína Supressora de Tumor p53/antagonistas & inibidores , Espécies Reativas de Oxigênio/antagonistas & inibidores , Ratos Wistar , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Proteína X Associada a bcl-2/antagonistas & inibidores , Caspase 3/efeitos dos fármacos , Eixo Hipotalâmico-Hipofisário-Gonadal/efeitos dos fármacosRESUMO
ABSTRACT The hypothalamic-pituitary-gonadal (HPG) axis is a key neuroen-docrine regulation system involved in the growth and reproduction of poultry. High-temperature conditions lead to the physiological dysfunction of target organs of the HPG axis of poultry, ultimately affecting the animals growth and development. In this study, we evaluated the effect of heat stress (HS) on the development of cells secreting major reproductive hormones of the HPG axis (i.e., hypothalamus, pituitary gland, ovary, and testis) of Wenchang chicks. Seventy-two one-day-old healthy Wenchang chicks were randomly divided into control (CK) and HS groups. The HS group was placed in a 40 ± 0.5°C artificial climate chamber for heat-stress treatment from 13:00 to 15:00 daily for six consecutive weeks. As development progressed, compared with the CK group, the gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels in the hypothalamus and testosterone (T) levers in the testes of male chicks in the HS group were significantly decreased at three weeks of age (p 0.05). However, GnRH levels in the hypothalamus and estradiol (E2) levels in the ovaries of female chicks in the HS group were variable and significantly lower than those of the CK group at four and five weeks of age (p 0.05). In addition, the LH and FSH levels in the pituitary gland were significantly lower than those in the CK group at two and four weeks of age and at four and six weeks of age, respectively (p 0.05). In brief, HS caused dysfunction of the corresponding target organs of the HPG axis in Wenchang chicks, and this affected the normal growth and development of the cells HPG axis.
RESUMO
This study conducted an in-depth investigation on the development of GABAergic neurons and their receptors in HPG axis-related target organs of Wenchang chicks under heat stress. One-day-old healthy Wenchang chicks were randomly divided into control (CK) and heat stress (HS) groups. Chicks in the HS group were placed in a 40±0.5°C climatic chamber for HS treatment from 13:00 to 15:00 daily. By immunohistochemistry and Western blotting, GABA and GABAA receptor (GABAAR) expression in the hypothalamus of the HS group was significantly higher (p 0.05), but GABAB receptor (GABABR) expression was significantly lower than that of the CK group (p 0.05). Expression of GABA and its two receptors in the pituitary tissues of the HS group was significantly lower than in the CK group (p 0.05). Expression of GABA and GABABR in ovaries in the HS group was significantly higher, but expression of GABAAR in the testes of the HS group was lower than that of the CK group (p 0.05). In the male chicks, expression of GABA and its two receptors in the hypothalamus, pituitary, and testicular tissues of the HS group was significantly higher than that of the CK group (p 0.05). Western blotting showed that the GABAAR and GABABR expression of the HS group was significantly higher than that of the CK group at 3 and 5 weeks of age. Thus, HS caused GABAergic nervous system disorder in the HPG axis of Wenchang chicks and seriously hindered the normal development of GABAergic neurons in chicks, leading to the disorder of the expression of GABA and its receptors in tissues.
Assuntos
Animais , Galinhas/fisiologia , Neurônios , Resposta ao Choque Térmico , Hipotálamo , Hipófise , Hormônios GonadaisRESUMO
This study conducted an in-depth investigation on the development of GABAergic neurons and their receptors in HPG axis-related target organs of Wenchang chicks under heat stress. One-day-old healthy Wenchang chicks were randomly divided into control (CK) and heat stress (HS) groups. Chicks in the HS group were placed in a 40±0.5°C climatic chamber for HS treatment from 13:00 to 15:00 daily. By immunohistochemistry and Western blotting, GABA and GABAA receptor (GABAAR) expression in the hypothalamus of the HS group was significantly higher (p 0.05), but GABAB receptor (GABABR) expression was significantly lower than that of the CK group (p 0.05). Expression of GABA and its two receptors in the pituitary tissues of the HS group was significantly lower than in the CK group (p 0.05). Expression of GABA and GABABR in ovaries in the HS group was significantly higher, but expression of GABAAR in the testes of the HS group was lower than that of the CK group (p 0.05). In the male chicks, expression of GABA and its two receptors in the hypothalamus, pituitary, and testicular tissues of the HS group was significantly higher than that of the CK group (p 0.05). Western blotting showed that the GABAAR and GABABR expression of the HS group was significantly higher than that of the CK group at 3 and 5 weeks of age. Thus, HS caused GABAergic nervous system disorder in the HPG axis of Wenchang chicks and seriously hindered the normal development of GABAergic neurons in chicks, leading to the disorder of the expression of GABA and its receptors in tissues.(AU)
Assuntos
Animais , Galinhas/fisiologia , Resposta ao Choque Térmico , Neurônios , Hipotálamo , Hipófise , Hormônios GonadaisRESUMO
The aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis functionality on a bodybuilding competitioner before, during and after the use of anabolic-androgenic steroids. A young healthy man was followed up for 4 months. The subject reported his drug administration protocol through periodic interviews and performed laboratory tests to monitor the function of his hypothalamic-pituitary-gonadal axis. Time 1 (before the steroids use) shows all hormones levels (follicle-stimulating hormone = 4,2 mUI/ml, luteinising hormone = 3,7 mUI/ml and total testosterone = 5,7 ng/ml) within reference values. In Time 2, after 8 weeks on steroids abuse, a complete hypothalamic-pituitary-gonadal axis derangement is evident with noticeable negative feedback (follicle-stimulating hormone = 1,47 mUI/ml, luteinising hormone = 0,1 mUI/ml and total testosterone = 1,47 ng/ml). At the third moment (40 days after Time 2), we can see a tendency to recovery, however, the serum levels of the investigated hormones were still considerably lower than the baseline values. At the end, we could conclude that the use of anabolic-androgenic steroids, at supraphysiological dosages, even for a short time (8 weeks), causes severe disorder in the hypothalamic-pituitary-gonadal axis. The endogenous testosterone synthesis was severely compromised by important decline in serum luteinising hormone levels.
Assuntos
Anabolizantes/efeitos adversos , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Congêneres da Testosterona/efeitos adversos , Testosterona/sangue , Anabolizantes/administração & dosagem , Humanos , Masculino , Doenças da Hipófise/sangue , Doenças da Hipófise/induzido quimicamente , Doenças Testiculares/sangue , Doenças Testiculares/induzido quimicamente , Congêneres da Testosterona/administração & dosagem , Adulto JovemRESUMO
Previous studies have shown that kisspeptin neurons are important mediators of prolactin's effects on reproduction. However, the cellular mechanisms recruited by prolactin to affect kisspeptin neurons remain unknown. Using whole-cell patch-clamp recordings of brain slices from kisspeptin reporter mice, we observed that 20% of kisspeptin neurons in the anteroventral periventricular nucleus was indirectly depolarized by prolactin via an unknown population of prolactin responsive neurons. This effect required the phosphatidylinositol 3-kinase signaling pathway. No effects on the activity of arcuate kisspeptin neurons were observed, despite a high percentage (70%) of arcuate neurons expressing prolactin-induced STAT5 phosphorylation. To determine whether STAT5 expression in kisspeptin cells regulates reproduction, mice carrying Stat5a/b inactivation specifically in kisspeptin cells were generated. These mutants exhibited an early onset of estrous cyclicity, indicating that STAT5 transcription factors exert an inhibitory effect on the timing of puberty.
Assuntos
Kisspeptinas/metabolismo , Fator de Transcrição STAT5/metabolismo , Maturidade Sexual , Transdução de Sinais , Animais , Núcleo Arqueado do Hipotálamo/citologia , Biomarcadores/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Hipotálamo Anterior/citologia , Potenciais da Membrana/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Prolactina/farmacologia , Maturidade Sexual/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fatores de TempoRESUMO
Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100ng/kg/day) for 15days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may be associated with abnormal HPG function. A strong negative correlation between the hyperleptinemia and lower Kiss responsiveness was observed in the TBT rats. These findings provide evidence that TBT leads to toxic effects direct on the HPG axis and/or indirectly by abnormal metabolic regulation of the HPG axis.
Assuntos
Hormônios Hipotalâmicos/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Kisspeptinas/metabolismo , Leptina/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Compostos de Trialquitina/toxicidade , Animais , Disruptores Endócrinos/toxicidade , Exposição Ambiental/efeitos adversos , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/metabolismo , Feminino , Hormônios Hipotalâmicos/antagonistas & inibidores , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Kisspeptinas/antagonistas & inibidores , Leptina/antagonistas & inibidores , Obesidade/induzido quimicamente , Obesidade/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Ratos , Ratos Wistar , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
O envelhecimento é considerado processo multidimensional no qual fatores ambientais podem proteger ou, inversamente, agravar seus sinais, de maneira não linear, nos processos fisiológicos e neurocomportamentais. Durante este processo, os ritmos circadianos são interrompidos ou fragmentados com dissociação consequente dos ritmos circadianos do indivíduo e disfunções relacionadas ao relógio circadiano contribuem para o envelhecimento e para patologias a ele relacionadas. O objetivo deste estudo foi averiguar possível alteração temporal do sistema CLOCK no eixo HPG e a relação com às alterações hormonais que caracterizam a periestropausa. Foram utilizadas fêmeas adultas com ciclo estral regular (CD) na fase do diestro e fêmeas senis com ciclo estral irregular e persistência da fase do diestro (IDP). Para análises de expressão gênica dos clock genes Per2, Rev-erbα e Bmal1 no eixo HPG, foram utilizados punchs das regiões do NSQ, onde também foi analisado RNAm de AVP, APO e HMB destes animais, além da adenohipófise e ovários dos quais se extraiu o RNA para confecção do cDNA e realização de qPCR. A determinação da atividade neuronal vasopressinérgica no NSQ foi realizada por imunoistoquíca com dupla marcação para cFos e AVP em tecido previamente fixado com paraformaldeído. A concentração plasmática de gonadotrofinas foi determinada por radioimunoensaio. De modo geral, os animais IDP revelaram alterações no perfil de expressão gênica durante o fotoperíodo, com redução de amplitude, deslocamento/desalinhamento de fase e ausência de antifase. O NSQ de animais IDP apresentou menor expressão de Rev-erbα e maior expressão de RNAm para AVP em relação ao grupo CD. A quantificação relativa de Bmal1 foi semelhante em ambos os grupos e não houve diferenças entre grupos na expressão de Per2. Na APO, animais IDP apresentaram maior expressão de Per2 e menor quantidade de RNAm para Rev-erbα. No HMB observou-se menor expressão para Per2 e Rev-erbα e maior expressão de Bmal1 nas fêmeas IDP. Per2 e Bmal1 na adenohipófise tiveram menor expressão que o gene Rev-erbα no grupo senil e o ovário destes animais revelou maior expressão para Per2 e Rev-erbα, em comparação com os animais CD. As concentrações plasmáticas de FSH foram maiores nas fêmeas com ciclo irregular (2,05 ± 0,44 ng/mL), principalmente durante a fase clara, assim como o LH (0,24 ± 0,07 ng/mL), cujos maiores valores foram encontrados durante a fase escura e com perfil semelhante ao RNAm de AVP. As imunomarcações revelaram alta atividade vasopressinérgica na porção dorsomedial do NSQ das fêmeas IDP. Juntos estes dados permitem concluir que há desarranjo na expressão temporal dos genes Per2, Rev-erbα, Bmal1 que compõem a maquinaria molecular do relógio circadiano, bem como de RNAm para AVP no NSQ, de fêmeas Wistar na periestropausa. Além disso, a maior atividade neuronal vasopressinérgica e a ausência de oscilação de Rev-erbα e Bmal1 no NSQ destes animais, comprometem a correta comunicação do relógio central do NSQ com o eixo HPG, inviabilizando a manutenção da fertilidade feminina e contribuindo para a senescência reprodutiva(AU)
Aging is considered a multidimensional process in which environmental factors can protect or, conversely, aggravate its signals, non-linearly, in physiological and neurobehavioral processes. During this process, circadian rhythms are disrupted or fragmented with consequent dissociation of the individual's circadian rhythms and circadian clock-related dysfunctions contribute to aging and related pathologies. The objective of this study was to investigate possible temporal alteration of the CLOCK system in the HPG axis and the relation with the hormonal changes that characterize periestropause. Adult females with regular estrus cycle in the diestrous phase (RD) and old females with irregular estrous cycle and persistent diestrous phase (IPD). For analyzes of the gene expression of the genes Per2, Rev-erbα and Bmal1 in the HPG axis, punchs from the NSQ regions were used, where AVP, POA and MBH RNAm from these animals were also analyzed, as well as the adenohypophysis and ovaries from which they were extracted the RNA for cDNA production and qPCR performance. The determination of the vasopressinergic neuronal activity in the NSQ was performed by immunohistochemical with double labeling for cFos/AVP in tissue previously fixed with paraformaldehyde. The plasma concentration of gonadotrophins was determined by radioimmunoassay. In general, the IPD animals show alterations in the gene expression profile during the period analyzed, with amplitude reduction, phase shift / misalignment and absence of antiphase. The NSQ of IPD animals presented lower expression of Rev-erbα and higher RNAm expression for AVP than RD group. The relative quantification of Bmal1 was similar in both groups and there were no differences between groups in the expression of Per2. In PAO, IPD animals showed higher expression of Per2 and less amount of RNAm for Rev-erbα. MBH showed lower expression for Per2 and Rev-erbα and higher Bmal1 expression in IPD females. Per2 and Bmal1 in the adenohypophysis had lower expression than the Rev-erbα gene in the old group and the ovary of these animals showed higher expression for Per2 and Rev-erbα, in related to to the RD animals. Plasma concentrations of FSH were higher in females with irregular cycle (2.05 ± 0.44 ng / mL), mainly during the light phase, as well as LH (0.24 ± 0.07 ng / mL) whose values were found during the dark phase and with a profile similar to AVP RNAm. Immunolabeling demonstrated high vasopressinergic activity in the dorsomedial portion of the NSQ of the IPD females. Together these data allow us to conclude that there is a breakdown in the temporal expression of the Per2, Rev-erbα, Bmal1 genes that make up the molecular machinery of the circadian clock, as well as RNAm for AVP in NSQ of Wistar females in peri-masterpause. In addition, the increased vasopressinergic neuronal activity and the absence of Rev-erbα and Bmal1 oscillation in the NSQ of these animals compromise the correct communication of the central clock of the NSQ with the HPG axis, making it impossible to maintain female fertility and contributing to reproductive senescence(AU)