Made available in DSpace on 2016-01-26T18:55:28Z (GMT). No. of bitstreams: 1 Dissertacao.pdf: 210803 bytes, checksum: 83b85718d8feaeb1014019b6a6feaea9 (MD5) Previous issue date: 2009-08-11 / The aim of study was to test the hormonal protocol for FTAI (fixed timed artificial insemination) with progesterone for 6 days applying eCG (Equine Corionic Gonadotrophin) or BE (Estradiol Benzoate) and induction of estrus using: MAP (acetato de medroxiprogesterone) for 6, 9 and 14 days or a single dose of PGF2a or male effect. Experiment 1: In D0 each ewe (n = 31) received CIDR being divided into 3 groups: GC (control) CIDR for 9 days and in withdrawal PGF2a + eCG. In G-eCG CIDR for 6 days PGF2a + eCG and in G-BE estradiol benzoate 24H after PGF2a and the FTAI 50H after the withdraw of CIDR. Experiment 2: On day 0 the sheeps (n = 48) received MAP being divided into 2 groups: G-9 and G-14 MAP by 9 or 14 days + PGF2a in withdrawal and detection of estrus. Experiment 3: divided up the sheeps (n = 151) in 3 groups: the G-6, each ewe received MAP for 6 days + PGF2a in withdrawal, the G-PGF, each ewe received PGF2a and G-EF only introducing ruffians. In exp. 1 pregnancy in the G-eCG (66%) was higher (p <0.05) in which G-BE (11.1%). In exp. 2 there were no differences (p <0.05) in estrus, pregnancy rate or design and in exp. 3 in G-6 (58%) and G-PGF (39%) the rate of estrus was greater (p <0.05) than in G-EF (11%). We concluded that is possible to reduce the time of permanence of progesterone using eCG for FTAI in sheep. / Objetivou-se testar o protocolo hormonal para IATF (inseminação artificial em tempo fixo) com progesterona por 6 dias aplicando-se eCG (gonadotrofina Coriônica Eqüina) ou BE (Benzoato de Estradiol) e indução de estros utilizando-se: esponjas vaginais impregnadas com MAP (acetato de medroxiprogesterona) por 6, 9 e 14 dias ou dose única de PGF2a ou efeito macho. Experimento 1: No D0 cada ovelha (n=31) recebeu CIDR sendo divididas aleatoriamente em 3 grupos: G-C (controle) CIDR por 9 dias e na retirada PGF2a + eCG. No G-eCG CIDR por 6 dias + PGF2a + eCG e no G-BE Benzoato de estradiol 24h após a PGF2a e a IATF 50 h após a retirada do CIDR. Experimento 2: No dia 0 as ovelhas (n=48) receberam MAP sendo divididas em 2 grupos: G-9 e G-14 MAP por 9 ou 14 dias + PGF2a na retirada e detecção de estro. Experimento 3: Dividiu-se aleatoriamente as ovelha (n=151) em 3 grupos: o G-6, cada ovelha recebeu MAP por 6 dias + PGF2a na retirada; o G-PGF, cada ovelha recebeu PGF2a e o G-EF apenas introdução de rufiões. No exp. 1 a prenhez no G-eCG (66%) foi maior (p<0,05) que no G-BE (11,1%). No exp. 2 não houve diferenças (p<0,05) no estro, taxa de prenhez ou de concepção. No exp. 3 no G-6 (58%) e G-PGF (39%) a taxa de estro foi maior (p<0,05) que no G-EF (11%). Concluímos ser possível reduzir o tempo de permanência da progesterona usando eCG para IATF em ovelhas

Made available in DSpace on 2016-07-18T17:53:06Z (GMT). No. of bitstreams: 1 Dissertacao.pdf: 210803 bytes, checksum: 83b85718d8feaeb1014019b6a6feaea9 (MD5) Previous issue date: 2009-08-11 / The aim of study was to test the hormonal protocol for FTAI (fixed timed artificial insemination) with progesterone for 6 days applying eCG (Equine Corionic Gonadotrophin) or BE (Estradiol Benzoate) and induction of estrus using: MAP (acetato de medroxiprogesterone) for 6, 9 and 14 days or a single dose of PGF2a or male effect. Experiment 1: In D0 each ewe (n = 31) received CIDR being divided into 3 groups: GC (control) CIDR for 9 days and in withdrawal PGF2a + eCG. In G-eCG CIDR for 6 days PGF2a + eCG and in G-BE estradiol benzoate 24H after PGF2a and the FTAI 50H after the withdraw of CIDR. Experiment 2: On day 0 the sheeps (n = 48) received MAP being divided into 2 groups: G-9 and G-14 MAP by 9 or 14 days + PGF2a in withdrawal and detection of estrus. Experiment 3: divided up the sheeps (n = 151) in 3 groups: the G-6, each ewe received MAP for 6 days + PGF2a in withdrawal, the G-PGF, each ewe received PGF2a and G-EF only introducing ruffians. In exp. 1 pregnancy in the G-eCG (66%) was higher (p <0.05) in which G-BE (11.1%). In exp. 2 there were no differences (p <0.05) in estrus, pregnancy rate or design and in exp. 3 in G-6 (58%) and G-PGF (39%) the rate of estrus was greater (p <0.05) than in G-EF (11%). We concluded that is possible to reduce the time of permanence of progesterone using eCG for FTAI in sheep. / Objetivou-se testar o protocolo hormonal para IATF (inseminação artificial em tempo fixo) com progesterona por 6 dias aplicando-se eCG (gonadotrofina Coriônica Eqüina) ou BE (Benzoato de Estradiol) e indução de estros utilizando-se: esponjas vaginais impregnadas com MAP (acetato de medroxiprogesterona) por 6, 9 e 14 dias ou dose única de PGF2a ou efeito macho. Experimento 1: No D0 cada ovelha (n=31) recebeu CIDR sendo divididas aleatoriamente em 3 grupos: G-C (controle) CIDR por 9 dias e na retirada PGF2a + eCG. No G-eCG CIDR por 6 dias + PGF2a + eCG e no G-BE Benzoato de estradiol 24h após a PGF2a e a IATF 50 h após a retirada do CIDR. Experimento 2: No dia 0 as ovelhas (n=48) receberam MAP sendo divididas em 2 grupos: G-9 e G-14 MAP por 9 ou 14 dias + PGF2a na retirada e detecção de estro. Experimento 3: Dividiu-se aleatoriamente as ovelha (n=151) em 3 grupos: o G-6, cada ovelha recebeu MAP por 6 dias + PGF2a na retirada; o G-PGF, cada ovelha recebeu PGF2a e o G-EF apenas introdução de rufiões. No exp. 1 a prenhez no G-eCG (66%) foi maior (p<0,05) que no G-BE (11,1%). No exp. 2 não houve diferenças (p<0,05) no estro, taxa de prenhez ou de concepção. No exp. 3 no G-6 (58%) e G-PGF (39%) a taxa de estro foi maior (p<0,05) que no G-EF (11%). Concluímos ser possível reduzir o tempo de permanência da progesterona usando eCG para IATF em ovelhas

Résumé : Le sFlt1 semble être un bon marqueur de la prééclampsie (PE). Nous avons évalué dans le cadre d’un essai randomisé contrôlé (MOMA), l’impact sur l’issue de grossesse d’un suivi rapproché de femmes identifiées comme « à risque » par un taux élevé de sFlt1 plasmatique entre 24 et 29 SA. Dans cet essai 939 nullipares ont été incluses en 2 bras (sflt1 connu ou non connu). Nos résultats ne montrent pas d’amélioration de l’issue de grossesse et suggèrent que l’inefficience de l’intervention (suivi rapproché) en est la cause la plus probable. Aussi la mesure du sFlt1 pour prédire la survenue d'une PE ne semble pas utile tant qu’un traitement efficace n’est pas à disposition. Des anomalies de la stéroïdogénèse placentaire ont été retrouvées associées à la PE. 90 échantillons issus de la cohorte MOMA répartis en trois groupes (25 PE, 25 retard de croissance intra utérin (RCIU) sans PE et 40 contrôles) ont été utilisés pour évaluer le profil stéroïdes par la technique fiable de GC/MS (entre 24 et 29 SA) - soit avant les signes cliniques -. Nous avons mis en évidence dans le groupe PE un défaut d'aromatisation des androgènes par le calcul du ratio estradiol/Δ4-Dione (sang) et un défaut d’expression de l’aromatase (placenta). Tout comme les taux significativement bas de sulfate de prégnénolone retrouvés, ce défaut d’aromatisation semble spécifique de la PE car ils n’ont pas été observés dans le groupe RCIU. Ces modifications s'inscrivent dans une dérégulation du profil stéroïdien global. Nous avons en effet observé dans les groupes PE et RCIU, un excés de 20α-dihydro-progestérone (20α-DHP) et un ratio 20α-DHP/Progestérone significativement élevé. Les stéroïdes sexuels partagent des voies de signalisation communes avec les facteurs angiogéniques, faisant inscrire aisément l’hypothèse « anomalies de la stéroïdogénèse » dans les concepts actuels de la physiopathologie de la PE. Les liens entre perturbations de la stéroïdogénèse et la prééclampsie sont discutés. / Abstract : sFlt1 appears to be a good biomarker of preeclampsia (PE). The impact on pregnancy outcomes of close monitoring of women identified as "at risk" at 24 and 29 weeks of gestation (weeks) by a high level of plasma sFlt1, was evaluated in a randomized controlled trial (MOMA). 939 nulliparous women were included in 2 arms (sFlt1 known or unknown). Our results do not show any improvement of pregnancy outcomes and suggest that the inefficiency of the intervention (close follow-up) is the most likely cause. Thus, routine sFlt1 screening to predict the occurrence of PE does not seem useful until effective treatment is available. Abnormalities of placental steroidogenesis have been associated with PE. 90 samples from the MOMA cohort divided into three groups (25 intra-uterine growth retardation (IUGR) without PE, 25 PE and 40 controls) were used to assess by the reliable GC / MS technique, the steroid profile (between 24 and 29 weeks)before the development of clinical signs. In the PE group, we showed abnormal androgen aromatization, by calculating the estradiol/Δ4-Dione ratio (blood), and a lack of expression of placental aromatase. Similarly to the significantly low levels of pregnenolone sulfate found, this lack of aromatization seems specific to PE as they are not found in the IUGR group. These modifications are part of a deregulation of the overall steroid profile. In the PE and IUGR groups, we observed an excess of 20α-dihydroprogesterone (20α-DHP) and a significantly high 20α-DHP/Progesterone ratio. Sex steroids share common signaling pathways with angiogenic factors which easily integrate the "steroidogenesis abnormalities" hypothesis in the current concepts in the pathophysiology of PE. Links between disturbances of steroidogenesis and preeclampsia are discussed.

MSCAGR / Department of Animal Science

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Endocrine disrupting compounds (EDCs) are exogenous compounds/chemicals in the environment that interfere with the synthesis, secretion, distribution and function or elimination of natural hormones in the body. Environmental estrogens are a subclass of EDCs that may mimic or inhibit the effect of endogenous estrogen and can therefore influence developmental and reproductive health in humans and animals. EDCs have been reported to adversely affect the reproductive, immune, endocrine and nervous systems of wildlife and humans. The effects of EDCs include gonadal abnormalities, altered male/female sex ratios, reduced fertility and cancers of the male and female reproductive tract to mention a few. These effects are difficult to detect. Although it is essential to screen for EDCs in aqueous environmental samples, most countries have failed to implement this as part of their routine water quality monitoring programs due to various constraints such as the high cost of assays and the lack of infrastructure and skills required to do the assays. Therefore, there is a clear need for more user-friendly, more economically viable and time saving assays that can be used for routine monitoring of environmental EDCs. The aim of this study was to investigate the comparison between chemical and tissue culture methods to monitor environmental estrogens. 28 environmental water samples were collected from various sites around South Africa and analyzed for EDCs using a battery of rapid in vitro tests. Samples collected for the current study were selected based on various human impacts and also to give approximately 50% high and 50% low estrogen values. The 28 environmental water samples were separated into two groups based on the estradiol ELISA. The estradiol ELISA was chosen because estradiol is the principal estrogen found in all mammalian species during their reproductive years. For this separation, an estradiol level of 5 pg/ml was used as cut-off. Of the 28 samples investigated, 15 had estradiol levels higher than 5 pg/ml and were designated as high estradiol. The remaining 13 samples contained estradiol at 5 pg/ml or less and they were designated as low estradiol The first objective of this study was to compare different rapid ELISAs for EDC monitoring to determine if the data obtained with these assays are similar/identical. The data obtained from the estrogenic ELISAs was related/similar and showed good correlation with each other. This is because the different estrogens are very similar and also due to the fact that the same sub-group in the population (the reproductively active females) is secreting these hormones. Therefore, an estradiol rapid assay was proposed as a first screening system for estrogens in samples. Even though there was a positive correlation between the estradiol rapid assay and testosterone rapid assay, separation of samples based on estradiol levels wasn’t a good predictor of testosterone levels in the samples. A testosterone rapid assay was therefore recommended as necessary to screen for androgens in samples. The positive correlation between the estradiol rapid assay and progesterone rapid assay was expected because both estradiol and progesterone are secreted and excreted by the same population sub-group (reproductively active females). This study also demonstrated a good predictability of separating samples containing progesterone using the estradiol ELISA. Progesterone is secreted by pregnant women, a sub-group of the reproductively active females. It is advised that a progesterone rapid assay be included to screen samples for progestogens The second objective of this study was to compare estradiol rapid ELISAs with a bioassay for anti-androgenicity using mouse testicular cell cultures. The mouse testicular cell testosterone synthesis bioassay to monitor anti-androgenicity of the samples showed no correlation between the ELISA data for estrogens. This study shows that anti-androgenic effects need to be monitored independently because the data for estrogenic compounds cannot be used as a predictor for anti-androgenic effects. This demonstrated the need for the inclusion of a mouse testicular cell testosterone synthesis bioassay to screen for androgenicity and anti-androgenicity of water samples. In summary, due to the different mechanisms of action of EDCs, this study recommended a battery of assays to monitor for EDCs. The battery of assays suggested is: v progesterone rapid assay was expected because both estradiol and progesterone are secreted and excreted by the same population sub-group (reproductively active females). This study also demonstrated a good predictability of separating samples containing progesterone using the estradiol ELISA. Progesterone is secreted by pregnant women, a sub-group of the reproductively active females. It is advised that a progesterone rapid assay be included to screen samples for progestogens. The second objective of this study was to compare estradiol rapid ELISAs with a bioassay for anti-androgenicity using mouse testicular cell cultures. The mouse testicular cell testosterone synthesis bioassay to monitor anti-androgenicity of the samples showed no correlation between the ELISA data for estrogens. This study shows that anti-androgenic effects need to be monitored independently because the data for estrogenic compounds cannot be used as a predictor for anti-androgenic effects. This demonstrated the need for the inclusion of a mouse testicular cell testosterone synthesis bioassay to screen for androgenicity and anti-androgenicity of water samples. In summary, due to the different mechanisms of action of EDCs, this study recommended a battery of assays to monitor for EDCs. The battery of assays suggested is: Estradiol ELISA as a rapid assay to screen for estrogens. Testosterone ELISA as a rapid assay to screen for androgens. Progesterone ELISA as a rapid assay to screen for progestogens. Mouse testicular cell testosterone synthesis bioassay to screen for androgenicity and anti-androgenicity.

Studies indicate that estrogen enhances Chlamydia trachomatis serovar E infection in genital epithelial cells. Hormones have direct and indirect effects on endometrial epithelial cells. Estrogen and progesterone exposure induces endometrial stromal cells to release effectors that subsequently regulate growth and maturation of uterine epithelial cells. Estrogen enhances C. trachomatis infection by aiding entry and intracellular development in endometrial epithelial cell (Ishikawa, IK)/SHT-290 stromal cell co-culture. Enhanced chlamydial infection was mediated by direct estrogen-stimulated signaling events in epithelial cells and indirectly via estrogen-induced stromal cell effectors. The current study investigates the effects of hormones on chlamydial development using culture conditions representative of the menstrual cycle. Chlamydia trachomatis-infected IK or IK/SHT-290 cultures were exposed to 10(-8) M estrogen (E2), 10(-7) M progesterone (P4) or a combination of both hormones (10(-8) M E2 followed by 10(-9) M E2/10(-7) M P4). Chlamydial infectivity and progeny production were significantly decreased (30-66%) in cultures exposed to progesterone or estrogen/progesterone combination compared to estrogen alone. Thus, progesterone antagonized the positive effects of estrogen on chlamydial infection. These data indicate the susceptibility of endometrial epithelial cells to C. trachomatis infection during the menstrual cycle is altered by phase specific actions of sex hormones in the genital tract.

Osmotic swelling of glial cells may contribute to the development of retinal edema. We investigated whether sex steroids inhibit the swelling of glial somata in acutely isolated retinal slices and glial cells of the rat. Superfusion of retinal slices or cells from control animals with a hypoosmolar solution did not induce glial swelling, whereas glial swelling was observed in slices of postis- chemic and diabetic retinas. Progesterone, testosterone, estriol, and 17ß-estradiol prevented glial swelling with half-maximal effects at approximately 0.3, 0.6, 6, and 20 lM, respectively. The effect of progesterone was apparently mediated by transactivation of metabotropic glutamate receptors, P2Y1, and adenosine A1 receptors. The data suggest that sex steroids may inhibit cytotoxic edema in the retina.

Metastatic bone cancers cause severe symptoms including pain that compromises patient functional status, quality of life, and survival. Current treatment strategies have limited efficacy and dose-limiting side effects. Cancer-induced bone pain (CIBP) is a unique pain state that shares features with but is distinct from the pathology of neuropathic and inflammatory pain. This dissertation investigates how CIBP is generated and maintained by the direct effects of cancer cells on their metastatic microenvironment and the peripheral nervous system, including unique signaling properties and gene expression changes. In particular, we found that genetic knockdown of the functional subunit xCT of the system xC- cystine/glutamate antiporter can reduce CIBP, further elucidating this as a therapeutic of interest. We found that the neuroprotective voltage-gated calcium channel inhibitors progesterone and pregabalin markedly reduce mechanical hypersensitivity and excitability in sensory neurons of the dorsal root ganglion (DRG) in male rat models of neuropathic pain, but that these effects and less pronounced in females. In cancer pain, these sex differences are reversed, with females but not males demonstrating a delay in time-to-onset of mechanical hypersensitivity. We also analyzed gene expression at the DRG by RNA-Sequencing of rat models of CIBP. Our findings uncovered differential gene expression between CIBP and sham controls and between ipsilateral and contralateral DRGs in CIBP model rats. These studies have identified several promising avenues for therapeutic research for CIBP. / Dissertation / Doctor of Philosophy (PhD) / The tools we have right now to manage severe and chronic pain are insufficient. Patients with advanced cancers including bone cancer can suffer from very severe pain. This pain is generated in a number of ways including by the tumour itself releasing chemicals that activate pain-sensing nerves, by the destruction of the bone in and around the tumour, and by the sensitization of the nervous system, which can make pain worse and longer lasting. We have taken three approaches to researching cancer pain and to investigating new treatments. We have found that by reducing the amount of glutamate that cancer cells can release into their environment, we can reduce cancer pain in mice. We also found that treating rats with pregabalin and progesterone can change nerve signaling and reduce neuropathic pain, but that this effect is most pronounced in male rats with neuopathic pain and smaller in female rats with neuropathic pain, and even smaller in rats with cancer pain. We also analyzed expression of all the protein-coding genes in dorsal root ganglia from rats with cancer pain and found that there are many differences from rats without pain. Some of these differences may be promising new research targets. Going forward this research has provided important evidence necessary for next steps to develop new therapies and research strategies for cancer pain.

Hormone-dependent cancers (HDCs), such as those of the prostate, ovary, breast and endometrium, share characteristics that indicate similar underlying mechanisms of carcinogenesis. Through steroid hormone signalling on "down-stream" target genes, the growth, development and progression of HDCs are regulated. One such family of target genes, highly expressed in HDCs and regulated by steroid hormones, are the tissue kallikreins (KLKs). The KLKs are a multigene family of serine proteases involved in physiological processes such as blood pressure regulation, inflammation, and tumour development and progression via the hydrolysis of specific substrates. Although the KLK gene family is clearly implicated in tumourigenesis, the precise roles played by these genes are largely unknown. Additionally, except for the androgen-responsive genes, KLK2 and KLK3, the mechanisms underlying their hormonal regulation in HDCs are yet to be identified. The initial focus of this thesis was to examine the regulation of the kallikreins, KLK1 and KLK4, by estradiol and progesterone in endometrial and breast cancer cell lines. From these studies, progesterone clearly regulated KLK4 expression in T47D cells and therefore, the focus of the remaining studies was to further examine this regulation at the transcriptional level. An overview of the results obtained is detailed below. Human K1 and hK4 protein levels were increased by 10 nmol/L estradiol benzoate, progesterone, or a combination of the two, over 48 hours in the endometrial cancer cell line, KLE. However, these same treatments resulted in no change in KLK1 gene or hK1 protein levels in the endometrial cancer cell lines, HEC1A or HEC1B (only hK1 analysed). Progesterone treatment (0-100 nmol/L) over 24 hours resulted in a clear increase in KLK4 mRNA at the 10 nmol/L dose in the breast cancer cell line, T47D. Additionally, treatment of T47D cells with 10 nmol/L progesterone over 0-48 hr, resulted in the rapid expression of the hK4 protein at 2 hr which was sustained for 24 hr. Further analysis of this latter progesterone regulation with the antiprogesterone, RU486, over 24 hours, resulted in an observable decrease in hK4 levels at 1 µmol/L RU486. Although the estrogen and progesterone regulation of the hK1 protein was not further analysed, the data obtained for hK4 regulation in T47D cell lines, supported the premise that this gene was progesterone-responsive. The rapid expression of hK4 protein by progesterone at two hours suggests that KLK4 transcription is directly coupled to progesterone regulation, perhaps through progesterone receptor (PR) binding to progesterone-responsive regions within the KLK4 promoter or far "up-stream" regions. Thus, the following further studies were performed. To test this hypothesis, the transcription initiation site (TIS) and 5' flanking regions of the KLK4 gene in T47D cells were interrogated. Primer extension and 5' RACE identified the TIS 78 bp 5' of the putative ATG site for translation as identified by Korkmaz et al. (2001). This KLK4 gene transcript consists of only four exons, and thus excludes the pre/pro signal peptide. Although a TATA-box is not present within -25 to -30 bp 5' of the identified TIS, a number of consensus binding motifs for Sp1 and estrogen receptor half-sites were identified. It is possible that the Sp1 sites are involved in the basal levels of transcription for this gene. Additionally, a putative progesterone response element (PRE) was identified in the far "up-stream" regions of the KLK4 gene. Basal levels of transcription were observed within the KLK4 proximal promoter region when coupled to a luciferase reporter gene and transfected into T47D cell lines. Additionally, the KLK4 proximal promoter region did not induce the luciferase reporter gene expression when progesterone was added to the system, however, estradiol was inhibitory for luciferase gene expression. This suggests that the proximal promoter region of the KLK4 gene could contain functional EREs but not PREs. In keeping with this hypothesis, some ER half-sites were identified, but PR sites were not obvious within this region. The identified PRE in the far "up-stream" region of the KLK4 gene assembled the progesterone receptor in vitro, and in vivo, as assessed by electromobility shift assays and chromatin immunoprecipitation assays (EMSAs and ChIPs), respectively. The binding of the PR to the KLK4 PRE was successfully competed out by a PR antibody and not by an androgen receptor antibody, and thus confirms the specificity of the KLK4 PRE-PR complex. Additionally, the PR was recruited and assembled onto and off the progesterone-responsive KLK4 region in a cyclic fashion. Thus, these data strongly suggest that the PR represents one of the core components of a transcription complex for the KLK4 gene, and presumably also contributes to the expression of this gene. Moreover, these data suggest a functional coordination between the PR and the KLK4 progesterone-responsive region in T47D cells, and thus, provide a model system to further study these events in vivo.

Orientador: Guilherme de Paula Nogueira / Banca: José Luis Moraes Vasconcelos / Banca: Ciro Moraes Barros / Resumo: Seis novilhas Nelore tiveram seus ciclos estrais acompanhados durante diferentes estações do ano (outono n=11; inverno n=8; primavera n=9; verão n=9) com exames ultrassonográficos diários para contar e mensurar folículos ≥3mm. Amostras de sangue foram colhidas a cada 12h para hormônio luteinizante (LH) e progesterona (P4), e a cada 3h do estro até a ovulação para caracterizar o pico de LH. Cinco novilhas ovariectomizadas receberam 17β-estradiol (2μg/kg/p.v.) em cada estação, e amostras de sangue foram colhidas depois disso a cada 3h para quantificação de LH. A diferença percentual mensal ( %) do peso não variou entre as estações. A concentração média de P4 no ciclo estral foi maior (p=0,001) e o número de folículos menor (p=0,001) durante o outono (2,5±0,2ng/mL; 7,8±0,1) e verão (2,9±0,3ng/mL; 6,8±0,2) comparado com o inverno (1,4±0,2ng/mL; 9,6±0,3) e primavera (1,6±0,2ng/mL; 9,7±0,3). Durante o inverno houve mais ciclos estrais com três (5 de 8) e durante o verão somente ciclos com duas ondas foliculares (p=0,009). Como a secreção de LH não variou, apesar da variação sazonal na concentração de P4, e como houve correlação negativa entre os valores máximos de P4 e a variação percentual do fotoperíodo (p=0,0056; r = -0,4465), uma variação sazonal na sensibilidade das células luteínicas ao LH precisa ser avaliada. Nas novilhas ovariectomizadas, a concentração circanual de LH sem o estímulo de estradiol foi significante (p=0,0214). A resposta de LH ao tratamento de estradiol foi menor no verão (0,8±0,2ng/mL vs 1,3±0,5ng/mL). Nós supomos que existe variação sazonal na sensibilidade hipotalâmica ao estradiol. / Abstract: Six Nelore heifers had their estrous cycle followed during different seasons of the year (autumn n=11; winter n=8; spring n=9 and summer n=9) with daily ultrasonographic exams to count and measure follicles ≥3mm. Blood was collected every 12h for luteinizing hormone (LH) and progesterone (P4), and every 3h from estrus until ovulation to characterize the LH peak. Five ovariectomized heifers were injected with 17β-estradiol (2μg/kg/LW) every season and blood samples were collected thereafter at 3h intervals for LH quantification. The monthly body weight percentile difference ( %) did not vary between seasons. Average P4 concentration for the cycle was higher (p=0.001) and follicle number lower during autumn (2.5±.2ng/ml; 7.8±.1) and summer (2.9±.3ng/ml; 6.8±.2) (p=0.001) compared to winter (1.4±.2ng/ml; 9.6±.3) and spring (1.6±.2ng/ml; 9.7±.3). During winter there were more estrous cycles with three follicle waves (5 out of 8) and during summer only cycles with two follicular waves (p=0.009). As LH secretion did not vary despite seasonal variation in P4 concentration and as there was a negative correlation between higher P4 values and daily percentile variation of photoperiod ( %, p=0.0056; r= -0.4465), a seasonal variation in luteal cell sensitivity to LH needs to be evaluated. In the ovariectomized Nelore heifers, the LH circanual concentration without estradiol stimulus was significant (p=0.0214). The LH response to estradiol treatment was lower in summer (0.8±.2ng/ml vs 1.3±.5ng/ml). We hypothesize there exists seasonal variation in hypothalamic sensitivity to estradiol. / Mestre