abstract: Though for most of the twentieth century, dogma held that the adult brain was post-mitotic, it is now known that adult neurogenesis is widespread among vertebrates, from fish, amphibians, reptiles and birds to mammals including humans. Seasonal changes in adult neurogenesis are well characterized in the song control system of song birds, and have been found in seasonally breeding mammals as well. In contrast to more derived vertebrates, such as mammals, where adult neurogenesis is restricted primarily to the olfactory bulb and the dentate gyrus of the hippocampus, neurogenesis is widespread along the ventricles of adult amphibians. I hypothesized that seasonal changes in adult amphibian brain cell proliferation and survival are a potential regulator of reproductive neuroendocrine function. Adult, male American bullfrogs (Rana catesbeiana; aka Lithobates catesbeianus), were maintained in captivity for up to a year under season-appropriate photoperiod. Analysis of hormone levels indicated seasonal changes in plasma testosterone concentration consistent with field studies. Using the thymidine analogue 5-bromo-2-deoxyuridine (BrdU) as a marker for newly generated cells, two differentially regulated aspects of brain cell neogenesis were tracked; that is, proliferation and survival. Seasonal differences were found in BrdU labeling in several brain areas, including the olfactory bulb, medial pallium, nucleus accumbens and the infundibular hypothalamus. Clear seasonal differences were also found in the pars distalis region of the pituitary gland, an important component of neuroendocrine pathways. BrdU labeling was also examined in relation to two neuropeptides important for amphibian reproduction: arginine vasotocin and gonadotropin releasing hormone. No cells co-localized with BrdU and either neuropeptide, but new born cells were found in close proximity to neuropeptide-containing neurons. These data suggest that seasonal differences in brain and pituitary gland cell neogenesis are a potential neuroendocrine regulatory mechanism. / Dissertation/Thesis / M.S. Biology 2012

abstract: For animals that experience annual cycles of gonad development, the seasonal timing (phenology) of gonad growth is a major adaptation to local environmental conditions. To optimally time seasonal gonad growth, animals use environmental cues that forecast future conditions. The availability of food is one such environmental cue. Although the importance of food availability has been appreciated for decades, the physiological mechanisms underlying the modulation of seasonal gonad growth by this environmental factor remain poorly understood. Urbanization is characterized by profound environmental changes, and urban animals must adjust to an environment vastly different from that of their non-urban conspecifics. Evidence suggests that birds adjust to urban areas by advancing the timing of seasonal breeding and gonad development, compared to their non-urban conspecifics. A leading hypothesis to account for this phenomenon is that food availability is elevated in urban areas, which improves the energetic status of urban birds and enables them to initiate gonad development earlier than their non-urban conspecifics. However, this hypothesis remains largely untested. My dissertation dovetailed comparative studies and experimental approaches conducted in field and captive settings to examine the physiological mechanisms by which food availability modulates gonad growth and to investigate whether elevated food availability in urban areas advances the phenology of gonad growth in urban birds. My captive study demonstrated that energetic status modulates reproductive hormone secretion, but not gonad growth. By contrast, free-ranging urban and non-urban birds did not differ in energetic status or plasma levels of reproductive hormones either in years in which urban birds had advanced phenology of gonad growth or in a year that had no habitat-related disparity in seasonal gonad growth. Therefore, my dissertation provides no support for the hypothesis that urban birds begin seasonal gonad growth because they are in better energetic status and increase the secretion of reproductive hormones earlier than non-urban birds. My studies do suggest, however, that the phenology of key food items and the endocrine responsiveness of the reproductive system may contribute to habitat-related disparities in the phenology of gonad growth. / Dissertation/Thesis / Doctoral Dissertation Biology 2014

abstract: Reproduction is energetically costly and seasonal breeding has evolved to capitalize on predictable increases in food availability. The synchronization of breeding with periods of peak food availability is especially important for small birds, most of which do not store an extensive amount of energy. The annual change in photoperiod is the primary environmental cue regulating reproductive development, but must be integrated with supplementary cues relating to local energetic conditions. Photoperiodic regulation of the reproductive neuroendocrine system is well described in seasonally breeding birds, but the mechanisms that these animals use to integrate supplementary cues remain unclear. I hypothesized that (a) environmental cues that negatively affect energy balance inhibit reproductive development by acting at multiple levels along the reproductive endocrine axis including the hypothalamus (b) that the availability of metabolic fuels conveys alterations in energy balance to the reproductive system. I investigated these hypotheses in male house finches, Haemorhous mexicanus, caught in the wild and brought into captivity. I first experimentally reduced body condition through food restriction and found that gonadal development and function are inhibited and these changes are associated with changes in hypothalamic gonadotropin-releasing hormone (GnRH). I then investigated this neuroendocrine integration and found that finches maintain reproductive flexibility through modifying the release of accumulated GnRH stores in response to energetic conditions. Lastly, I investigated the role of metabolic fuels in coordinating reproductive responses under two different models of negative energy balance, decreased energy intake (food restriction) and increased energy expenditure (high temperatures). Exposure to high temperatures lowered body condition and reduced food intake. Reproductive development was inhibited under both energy challenges, and occurred with decreased gonadal gene expression of enzymes involved in steroid synthesis. Minor changes in fuel utilization occurred under food restriction but not high temperatures. My results support the hypothesis that negative energy balance inhibits reproductive development through multilevel effects on the hypothalamus and gonads. These studies are among the first to demonstrate a negative effect of high temperatures on reproductive development in a wild bird. Overall, the above findings provide important foundations for investigations into adaptive responses of breeding in energetically variable environments. / Dissertation/Thesis / Doctoral Dissertation Biology 2018

abstract: Ethinyl estradiol, (EE) a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives (Shively, C., 1998), and is found in at least 30 different contraceptive formulations currently prescribed to women (Curtis et al., 2005). EE is also used in hormone therapies prescribed to menopausal women, such as FemhrtTM (Simon et al., 2003). Thus, EE is prescribed clinically to women at ages ranging from puberty through reproductive senescence. Here, in two separate studies, the cognitive effects of cyclic or tonic EE administration following ovariectomy (Ovx) were evaluated in young, female rats. Study I assessed the cognitive effects of low and high doses of EE, delivered tonically via a subcutaneous osmotic pump. Study II evaluated the cognitive effects of low, medium, and high doses of EE administered via a daily subcutaneous injection. For these studies, the low and medium doses correspond to the range of doses currently used in clinical formulations, and the high dose corresponds to the range of doses prescribed to a generation of women between 1960 and 1970, when oral contraceptives first became available. For each study, cognition was evaluated with a battery of maze tasks tapping several domains of spatial learning and memory. At the highest dose, EE treatment impaired multiple domains of spatial memory relative to vehicle treatment, regardless of administration method. When given cyclically at the low and medium doses, EE did not impact working memory, but transiently impaired reference memory during the learning phase of testing. Of the doses and regimens tested here, only EE at the highest dose impaired several domains of memory; this was seen for both cyclic and tonic regimens. Cyclic and tonic delivery of low EE, a dose that corresponds to doses used in the clinic today, resulted in transient and null impairments, respectively, on cognition. / Dissertation/Thesis / M.A. Psychology 2012

Orientadores: Irani Quagio-Grassiotto, Maria Ines Borella / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-06T21:58:16Z (GMT). No. of bitstreams: 1 Nobrega_RafaelHenrique_M.pdf: 10312793 bytes, checksum: 13a65bc78504251ac2368131cd7f57fd (MD5) Previous issue date: 2006 / Resumo: Nos peixes teleósteos, a unidade morfofuncional da espermatogênese é o espenrmatocisto ou cisto, constituído por células germinativas, em desenvolvimento sincrônico, envoltas perifericamente pelas células de Sertoli. Em função da cinética da espermatogênese e do tipo de reprodução (contínua ou sazonal), o epitélio germinativo pode se desenvolver de forma constante ou sofrer modificações cíclicas durante o ciclo reprodutivo. O presente trabalho teve como objetivo analisar, através de parâmetros histológicos, ultra-estruturais e imuno-histoquímicos, as alterações do epitélio germinativo em duas espécies de ciclos reprodutivos diferentes (Serrasalmus spilopleura - reprodução contínua e Pimelodus maculatus - reprodução sazonal) e correlacioná-las com as células esteroidogênicas e as células gonadotrópicas, no intuito de melhor compreender a fisiologia reprodutiva dos teleósteos tropicais de água doce. Em S. spilopleura, o epitélio germinativo organiza-se em cistos basais de espermatogônias e cistos apicais de células germinativas em desenvolvimento mais avançado. As espermatogônias basais apresentam intensa atividade proliferativa durante todo o ciclo reprodutivo. As células de Sertoli proliferam no intuito de acompanhar o crescimento dos cistos e aumentar o tamanho do testículo a cada ciclo reprodutivo. Quanto à esteroidogênese, a atividade 3"beta"-HSD é maior na região espermatogênica do que na região relacionada à espermiação. Em relação às células gonadotrópicas, as células LH são requeridas durante a espermatogênese e na espermiação, enquanto que as células FSH são mais ativas na liberação dos espermatozóides e provavelmente na proliferação das células sle Sertoli. Em P. maculatus, o epitélio germinativo passa por modificações morfofuncionais, categorizadas em quatro classes reprodutivas: regredida, maturação, maturação final e regressão. A proliferação das espermatogônias é intensa durante a maturação e depois diminui na maturação final e regressão. As células de Sertoli proliferam em maior freqüência na classe regredida, o que contribui para o crescimento do testículo durante o ciclo reprodutivo. A atividade 3"beta"-HSD é intensa na maturação e na maturação final, e depois diminui na regressão e na classe regredida. Os processos de espermatogênese e liberação de espermatozóides são dependentes de andrógenos. As células LH e FSH estão em maior quantidade durante a maturação e a maturação final, e depois diminuem na regressão e na classe regredida. A espermatogênese e a liberação dos espermatozóides são mais dependentes da atividade gonadotrópica do que os processos de proliferação espermatogonial e regressão testicular / Abstract: In teleost fish, the morphofuncional unit of the spermatogenesis is the spermatocyst or cyst, which are constituded by synchronous developmental germ cells surrounded by Sertoli cells. Depending on the spermatogenesis kinetics and the type of reproduction (continuous/non-seazonal or seazonal), the germinal epithelium may be constant or undego cyclical changes during the reproductive cyc1e. The aim, of the present work is to analyze, through histological, ultrastructural and immunohistochemical evaluation, the changes of the germinal epithelium in two different reproductive cycles (Serrasalmus spilopleura continuous/non-seazonal reproduction and Pimelodus maculatus - seazonal reproduction) and to correlate them with steroidogenic cells and gonadotropic cells, for a better knowledge on the reproductive physiology of the tropical fresh water teleosts. In S. spilopleura, the germinal epithelium was organized in basal cysts of spermatogonia and apical cysts of more advanced developmental germ cells. The basal spermatogonia had intense proliferative activity during the whole reproductive cycle. Sertoli cells proliferation occured in order to accompany the cyst growth and to increase the testis size during each reproductive cycle. For steroidogenic activity, 3"beta"-HSD was stronger in the spermatogenic area than in the area related to spermiation. In re1ation to gonadotropic cells, LH cells were requ~sted during spermatogenesis and spermiation, whereas FSH cells were more active in spermatozoa liberation and probably in the Sertoli celI proliferation. In P. maculatus, the germinal epithelium undergoes morphological changes, classified in 4 reproductive classes: regressed, maturation, final maturation and regression. The spermatogonial prolif~ration was intense during maturation and decreased in final maturation and regression. Sertoli cells proliferated more in regressed class, contributing to testis growth during the reproductive cycle. The 3"beta"-HSD activity was strong in maturation and final maturation, and decreased in regression and in regressed class. Then, spermatogenesis processes and spermatozoa release are dependent of androgenic. LH and FSH cells were in large number during maturation and final maturation, and decreased in regression and in regressed class. In P. maculatus, spermatogenesis and spermatozoa release are more dependent of the gonadotropic activity than the processes such as spermatogonial proliferation and testicular regression / Mestrado / Biologia Celular / Mestre em Biologia Celular e Estrutural

O presente trabalho teve como objetivo estudar a psicodinâmica das Representações Sociais (RS) de endocrinologistas de hospital público sobre obesidade, identificando-as e buscando detectar seu inconsciente relativo, ou seja, a lógica emocional segundo a qual se estruturam. Foram realizadas 10 (dez) entrevistas com médicos endocrinologistas de rede pública, (05 do sexo feminino e 05 do sexo masculino) com idade variável de 28 a 44 anos de idade. O tempo de especialização variou de dois a dezoito anos. As entrevistas foram semi-estruturadas, no sentido de haver uma pré-estrutura mínima, permitindo ao entrevistado espontaneidade e fluência de expressão. Usou-se técnicas encobertas, com perguntas gerais e abrangentes. Desejou-se que o tema - obesidade - surgisse espontaneamente. O tratamento dos dados foi de acordo com o referencial psicodinâmico, numa abordagem qualitativa. Conclui-se que o médico é o intérprete das ideologias socialmente circulantes a respeito da obesidade. Suas condutas são pautadas pelas características de personalidade, pelas informações científicas, e pela influência midiática / Not informed by the author

O GLUT4 (gene Slc2<font face=\"symbol\">a4) é responsável pela captação de glicose sob estímulo insulínico, e alterações na sua expressão se relacionam à resistência à insulina (RI). Variações na concentração de estradiol (E2) estão relacionadas a RI e menor expressão deste transportador, mecanismo que pode ser mediado pelo fator transcricional NF<font face=\"symbol\">k-B, um repressor de Slc2<font face=\"symbol\">a4. Avaliou-se em células 3T3-L1 a regulação da expressão de Slc2<font face=\"symbol\">a4/GLUT4, a atividade de ligação de NF<font face=\"symbol\">k-B e a captação de glicose pelo E2 e o papel de ESR1 (isoforma 1 do receptor de E2) nesta regulação. Tratou-se as células por 1 dia com E2 e PPT (agonista de ESR1). O PPT aumentou a expressão de Slc2<font face=\"symbol\">a4/GLUT4 na ausência ou presença de E2 bem como a captação de glicose e diminuiu a atividade de ligação de NF<font face=\"symbol\">k-B. Os resultados apresentados demonstram que o E2, atuando via ESR1 aumenta a expressão de Slc2<font face=\"symbol\">a4/GLUT4, efeitos estes parcialmente mediados por NF<font face=\"symbol\">k-B, resultando em alteração na captação de glicose. / GLUT4 (gene Slc2<font face=\"symbol\">a4) is responsible by insulin-induced glucose uptake and alterations in its expression are related to insulin resistance (IR). Variability in estradiol levels (E2) is related with IR and lower glucose transporter expression and this mechanism can be mediated by transcriptional factor NF<font face=\"symbol\">k-B, which is an Slc2<font face=\"symbol\">a4 repressor. Our aim was to evaluate in 3T3-L1 adipocytes the role of E2 in Slc2<font face=\"symbol\">a4/GLUT4 expression, NF<font face=\"symbol\">k-B binding activity and glucose uptake as well as the ESR1 (estrogen receptor 1) role in this regulation. For this, 3T3-L1 cells were treated for 1 day with E2 and PPT (ESR1-agonist). PPT enhanced Slc2<font face=\"symbol\">a4/GLUT4 expression in the absence or presence of E2 as well as the glucose uptake and decreased NF<font face=\"symbol\">k-B binding activity. Our results show that E2 increases Slc2<font face=\"symbol\">a4/GLUT4 expression via ESR1 and this effect is partially mediated by NF<font face=\"symbol\">k-B, and allow parallel changes in glucose uptake.

PANcreatic-DERived factor (PANDER, FAM3B) has been shown to regulate glycemic levels via interactions with both pancreatic islets and the liver. Although PANDER is predominantly expressed from the endocrine pancreas, recent work has provided sufficient evidence that the liver may also be an additional tissue source of PANDER production. At physiological levels, PANDER is capable of disrupting insulin signaling and promoting increased hepatic glucose production. As shown in some animal models, strong expression of PANDER, induced by viral delivery within the liver, induces hepatic steatosis. However, no studies to date have explicitly characterized the transcriptional regulation of PANDER from the liver. Therefore, our investigation elucidated the nutrient and hormonal regulation of the hepatic PANDER promoter. Initial RNA-ligated rapid amplification of cDNA ends identified a novel transcription start site (TSS) approximately 26 bp upstream of the PANDER translational start codon not previously revealed in pancreatic β-cell lines. Western evaluation of various murine tissues demonstrated robust expression in the liver and brain. Promoter analysis identified strong tissue-specific activity of the PANDER promoter in both human and murine liver-derived cell lines. The minimal element responsible for maximal promoter activity within hepatic cell lines was located between -293 to -3 of the identified TSS. PANDER promoter activity was inhibited by both insulin and palmitate, whereas glucose strongly increased expression. The minimal element was responsible for maximal glucose-responsive and basal activity. Co-transfection reporter assays, chromatin-immunoprecipitation (ChIP) and site-directed mutagenesis revealed that the carbohydrate-responsive element binding protein (ChREBP) increased PANDER promoter activity and interacted with the PANDER promoter. E-box 3 was shown to be critical for basal and glucose responsive expression. In summary, in-vitro and in-vivo glucose is a potent stimulator of the PANDER promoter within the liver and this response may be facilitated by ChREBP.

M.Sc. (Zoology) / The histomorphology of the ovaries of Cyprinus carpio L., as well as the histomorphological changes that occur in these ovaries during the breeding cycle, were investigated. Concurrently, the blood plasma and ovarian cytosol were analized for the presence of gonadotropin (GtH), FSH, LH, Oestriol, Cortisol and Progesterone, with the aid of Test Kits which are commonly used for determining the levels of these hormones in human blood plasma. C. carpio possesses cystovaria which are continuous with the oviducts which unite before opening to the exterior via a gonopore. The results clearly show that C. carpio has a four season breeding cycle and that egg laying occurs during Spring and Summer. Furthermore morphological changes of the ovary (which occurred during the breeding cycle) as well as the oocyte developmental stages, closely resemble those respectively described for teleosts in general by Kesteven (1960) and Malhotra et al., (1978). The endocrinological tests clearly indicated the presence of GtH, FSH, LH, Oestriol and Cortisol, while all the tests for Progesterone were negative. A comparison between the presence of the abovementioned hormones and the histomorphological development of the ovaries during the breeding cycle indicate that the endocrinological control mechanisms are similar to those which have been described for other teleosts. However, a clear distinction was found between FSH and LH which is a possible indication that C. carpio does not possess a single gonadotropin, but rather that FSH and LH have evolved in this species.

A large number of man-made chemicals are present in the environment as pollutants and are capable of disrupting the endocrine system of animals and humans. Small-sized industry is an area where such chemicals are used and produced in abundance. There is no legislation governing the use, production and disposal of such chemicals, which studies have shown are posing a hazard to workers themselves and the surrounding communities. Run off water from seven sites in an area in Pretoria West, with significant numbers of small-sized industries, was screened for oestrogenicity, using the Recombinant Yeast Cell Bioassay (RCBA). Chemical analyses were done for the presence of endocrine disrupting chemicals (EOCs), including p-nonylphenol (p-NP), bisphenol A (BPA), phthalate esters, polychlorinated biphenyls (PCBs) and various organochlorine pesticides, including dichlorodiphenyltrichloroethane (DDT). The p-NP, PCBs and organochlorine pesticides were detected using a South African Bureau of Standards (SABS) in-house method: AM178 and the time of flight spectrometer, while the BPA and phthalates were detected using the CSIR Biochemtek Laboratory in-house GC-MS method: AM 186 based on the US EPA 8260 and the gas chromatography-mass spectrometer. The water tested positive for oestrogenic activity at all the sample sites and a significant amount of lindane, an organochlorine pesticide, was detected at one site. p-NP as well as phthalate esters were identified at different sites. No pattern or relationship could be established between the oestrogenic activity and the subsequent endocrine disrupting chemicals tested for. These EOCs in the water could pose a health risk for humans and animals. Further specific studies are needed to establish the possible sources of these contaminants, from industry and households. / Dissertation (MMed)--University of Pretoria, 2005. / School of Health Systems and Public Health (SHSPH) / Unrestricted