Pouco se conhece acerca dos aspectos fisiológicos da reprodução de ranfastídeos, sendo estas informações importantes para sua conservação e criação em cativeiro. Métodos não-invasivos permitem análises a longo prazo e em espécies pequenas, além de facilitar estudos em vida livre e minimizar o estresse causado aos animais. Este trabalho teve por intuito a dosagem de metabólitos de testosterona (machos e fêmeas), progesterona e estradiol (somente fêmeas) nas excretas de 3 casais de tucano-toco (Ramphastos toco) e 3 casais de tucano-de-bico-verde (Ramphastos dicolorus), dentro e fora da estação reprodutiva. Dados de observações comportamentais mostraram que os animais foram mais ativos durante a estação reprodutiva, porém comportamentos sociais e proximidade entre o casal se mostraram raros nas duas fases durante as seções de observação. Concentrações de metabólitos de progesterona foram obtidos para as duas espécies na Fase Reprodutiva, mas não foram detectados nos ensaios para a Fase Não-reprodutiva. Metabólitos de testosterona puderam ser dosados em ambas as espécies, nas duas fases, tanto em machos quanto em fêmeas; sendo que os resultados mostraram para a maioria dos indivíduos concentrações maiores na Fase Reprodutiva. Aumentos acima de variações basais de metabólitos de testosterona foram associados à ocorrência de posturas, que ocorreram durante a Fase Reprodutiva numa das fêmeas de R. toco. Não foram obtidos resultados de metabólitos de estradiol em nenhuma das duas espécies, possivelmente pela falha do anticorpo utilizado em reconhecer os metabólitos. No entanto, este trabalho mostrou que a técnica utilizada foi eficaz para dosagem de metabólitos de testosterona e progesterona nas excretas destas espécies, evidenciando variações sazonais nas concentrações hormonais e indicando uma relação entre a concentração de metabólitos de testosterona e as posturas. / Little is known about reproductive physiology in Ranfastidae and this knowledge is needed for the development of conservation programs and for successful captive breeding. Non-invasive methods allow long-term analysis in small animals, facilitate studies with free-living animals and minimize the handling stress. The purpose of this work was to measure the testosterone (males and females), progesterone and oestrogen (females) metabolites concentrations in the droppings of Toco-toucan (Ramphastos toco) and Red-billed-toucan (Ramphastos dicolorus), inside and outside the reproductive season. Three captive couples of each species were studied. Collected behavioural data showed that the animals were more active during reproductive season, but social behaviours and the couple proximity were rare in the two phases during the observation sessions. Progesterone metabolites concentrations could be obtained in the Reproductive Phase for both species, but weren`t detected in the Nonreproductive Phase. Testosterone metabolites could be measured for both species in the two phases, in males and females; and the results showed higher concentrations in most of individuals in the Reproductive Phase. Concentrations of testosterone metabolites above basal levels were associated to egg laying, which occurred during Reproductive Phase in one of the R. toco females. Results of oestrogen metabolites concentrations could not be obtained in both species, probably because the fail of the antibody in detecting these metabolites. However, this work showed that the utilized technique was efficient to measure testosterone and progesterone metabolites in those species droppings, evidencing seasonal variations in hormonal concentrations and indicating a relationship between testosterone concentrations and oviposition.

Quatro experimentos foram realizados para avaliar as concentrações plasmáticas de progesterona ([P4]) e as taxas de fertilidade na inseminação artificial em tempo fixo (IATF) após o uso de diferentes dispositivos de liberação lenta de progesterona (DP). No primeiro experimento foram utilizadas 4 novilhas ovariectomizadas. Esses animais receberam 5 diferentes tipos de DP, nos quais se variou a superfície de contato (50cm² ou 100 cm² e a dose de progesterona (0,5g; 1,0g e 2,0g) Os dispositivos foram inseridos aos pares durante 7 dias e se estabeleceu um intervalo entre tratamentos de pelo menos 30 dias. Com os dados de [P4] 24 horas e sete dias após a inserção do DP obtiveram-se as seguintes equações de regressão, respectivamente: [P4]24h = 0,238 + 0,0343(área) + 0,513(dose); (R²=0,94) e [P4] 7d = 0,331+ 0,0056(área) + 0,329(dose); (R²=0,71). No segundo experimento foram comparados dois dos dispositivos testados no primeiro estudo: P50-1,0 (50 cm2 área; 1,0g dose P4) e P50-1,5 (50 cm² área; 1,5g dose P4) com dois dispositivos comerciais: CIDR (120 cm² área; 1,9g P4 dose) e DIB (120 cm² área; 1,0g P4 dose). Os dispositivos foram inseridos em 15 novilhas Nelore pré-puberes para avaliação das [P4] obtendo-se, após 24 horas de inserção, para CIDR, DIB, P50-1,5 e P50-1,0, respectivamente: 7,7±2,8ª ; 4,5±0,75b; 5,9±2,5b e 2,1±0,5c ng/ml e após 8 dias, respectivamente: 3,3±0,7ª ; 2,6±2,0ª; 3,0±2,4ª e 1,1±0,27bng/ml. As regressões obtidas no primeiro experimento não foram eficientes para estimar as [P4] obtidas no estudo 2. Nos experimentos 3 e 4 comparou-se a eficiência dos dispositivos DIB e P50-1,5 em 431 vacas de corte zebuínas e cruzadas, com bezerros ao pé e multíparas, após uso em um programa de IATF no qual os dispositivos permaneciam nos animais durante 8 dias; quando da colocação desses dispositivos, eram aplicados 2mg de benzoato de estradiol (BE) e, na retirada, 400UI de eCG. Uma última dose de BE foi administrada 24 horas após a retirada dos DP, e a IATF foi realizada 54 horas após a retirada dos DP. Não foram encontradas diferenças nas taxas de concepção da IATF entre dispositivos. As taxas de concepção variaram entre 30 e 51,6% nos lotes tratados. O tratamento diminuiu o intervalo tratamento-parto de 365 para 317 dias, comparado à monta natural. / Four studies have been made to evaluate the plasmatic progesterone concentration ([P4]) of different intravaginal low delivery progesterone devices (PD) and the fertility rates after their use in timed artificial insemination (TAI). In the first study there were used 4 ovariectomized heifers. These animals received 5 kinds of prototypes PD on which varied the contact surface (50 or 100 cm²) and the progesterone doses (0,5; 1,0 or 2g). These PD were inserted in the vaginas in pairs and the interval between treatments was higher than 30 days. With the data of [P4] there were found the fallowing regressive equations for the days 1 and 7 after the insertion , respectively: [P4]24h = 0,238 + 0,0343(surface) + 0,513(dose); (R²=0,94) and [P4]7d = 0,331+ 0,0056(surface) + 0,329(dose); (R²=0,71). In the second study there were compared 2 prototypes PD based on the first study: P50-1,0 (50 cm² surface; 1,0g dose P4) and P50-1,5 (50 cm² surface; 1,5g dose P4) with two commercial PD: CIDR (120 cm² surface; 1,9g P4 dose) and DIB (120 cm² surface; 1,0g P4 dose). These PD were inserted in 15 prepuberal Nelore heifers to evaluate the [P4] The [P4] (in ng/ml) found after 24 hours were for CIDR, DIB, P50-1,5 e P50-1,0, respectively: 7.7±2.8ª ; 4.5±0.75b; 5.9±2.5b e 2.1±0.5c ng/ml and after 8 days, respectively: 3.3±0.7ª ; 2.6±2.0ª; 3.0±2.4ª e 1.1±0.27b ng/ml. The regressive equations found in the first study were not efficient to estimate the [P4] for the prototypes PDs. In the studies 3 and 4 there were compared the PD DIB and P50-1.5 for TAI in 431 Nelore and cross-breed lactating postpartum beef cows. The TAI protocol was: PD insertion per 8 days, administration of 2 mg estradiol benzoate (EB) in the insertion day - 400 UI of eCG in the PD removal - 1mg EB 24 hours after PD removal- TAI 54 hours after the PD removal. There were no differences in TAI conception rates between PD. The TAI conception rates ranged from 30 to 51.6% in the treated herds. The treatment has decreased the treatment-partum interval from 365 to 317 days on animals submitted to natural mating.

O objetivo do experimento I foi avaliar a redução do tempo de permanência do dispositivo de P4 de 9 para 7 dias sob parâmetros reprodutivos de vacas Nelore. Foram utilizadas 674 vacas lactantes entre 40-60 dias pós parto que receberam no início do protocolo (d0) BE + CIDR. No momento da retirada do CIDR foi administrado PGF2 &#945;, ECP e eCG. A IATF ocorreu 55 e 48 horas após a retirada do dispositivo nos tratamentos 7d-CIDR e 9d-CIDR, respectivamente. Dez dias após a IA foi realizada colheita de sangue para dosagem de P4 sérica e confirmação da ovulação. Vacas tratadas com 7d-CIDR apresentaram menor (p < 0,01) folículo ovulatório em relação ao 9d-CIDR. No entanto, a concentração de P4 pós-IA, taxas de ovulação, detecção de estro e prenhez não foram influenciadas pelo tempo de permanência do CIDR. Assim, o uso do CIDR por 7 dias promoveu desempenho reprodutivo semelhante em vacas Nelore comparado ao protocolo com 9 dias. O experimento II teve o objetivo de avaliar os efeitos da reutilização do CIDR por até 35 dias de uso em vacas e 42 dias em novilhas Nelore. Utilizou-se 749 vacas lactantes 40-60 dias pós parto e 92 novilhas púberes. No d0 os animais receberam BE + CIDR novo (CIDR1) ou previamente usado por 7 (CIDR2), 14 (CIDR3), 21 (CIDR4), 28 (CIDR5) e 35 (CIDR6) dias. No momento da retirada do CIDR (d7) foi administrado PGF2 &#945;, ECP, eCG e exame de US para mensuração do maior folículo (FD), além de colheita de sangue para dosagem de P4. A IATF ocorreu 55 horas após a retirada do dispositivo. O diâmetro do FD foi maior (p < 0,01) de acordo com o maior número de usos do CIDR nas vacas, a concentração de P4 reduziu nos CIDRs reutilizados porém se mantiveram acima de 1,5 ng/ml e a taxa de prenhez não foi afetada pela reutilização do dispositivo por até 5 vezes em vacas e o sexto uso em novilhas. O protocolo com 7 dias de permanência permite a reutilização do CIDR por até 6 vezes mantendo a mesma eficiência reprodutiva. No experimento III o objetivo foi avaliar se a aplicação do eCG dois dias antes da retirada do dispositivo aumenta o tamanho do FO, CL e taxa de prenhez. Foram utilizadas 681 vacas lactantes 40-60 dias pós parto e 182 novilhas púberes. Os animais foram distribuídos em dois tratamentos com aplicação de eCG no quinto (5d-eCG) ou sétimo dia (7d-eCG). No d0, os animais receberam BE + CIDR e no dia 7 o CIDR foi retirado e administrado PGF2 &#945; e ECP. Dez dias após a IA foi realizada US para mensuração do CL e colheita de sangue para dosagem de P4. A IATF ocorreu 55 horas após a retirada do dispositivo. O tratamento 5d-eCG aumentou (p < 0,01) o FO nas vacas em relação ao grupo 7deCG e o mesmo ocorreu nas novilhas. Em vacas, a concentração de P4 pós IA foi mais alta (p = 0,04) no 5d-eCG. Em novilhas o diâmetro do CL pós-IA foi maior (p < 0,01) no 5d-eCG. No entanto, a antecipação da aplicação do eCG foi eficiente em aumentar o folículo ovulatório no momento da IATF, mas não aumentou a taxa de prenhez / The aim of the experiment I was to evaluate the reduction of the time of P4 device from 9 (9d-CIDR) to 7 (7d-CIDR) days and its impacts on reproductive parameters of Nellore cows. Six hundred and seventy-four suckling cows 40-60 days postpartum received EB + CIDR at d0 of the protocol. At CIDR removal, there were administered PGF2 &#945;, ECP, eCG. The FTAI occurred 55 and 48 hours after device removal in the treatment 7d-CIDR and 9d-CIDR, respectively. Ten days after AI blood samples were collected for P4 analysis and ovulation rate. Cows of treatment 7d-CIDR showed lower (p <0.01) ovulatory follicle (OF) than 9d-CIDR. The CIDR length in cows and heifers did not influence concentration of P4, ovulation rate, estrus detection rate and pregnancy rate. Thus, the use of CIDR by 7 days did not impacted reproductive result in suckling cows and Nellore heifers. The aim of experiment II was to evaluate the effects of the CIDR reuse up to 35 days in cows and heifers on reproductive characteristics. We used 749 suckling cows 40-60 days postpartum and 92 pubertal heifers. In d0 animals received EB + new CIDR (CIDR1) or previously used by 7 (CIDR2), 14 (CIDR3), 21 (CIDR4), 28 (CIDR5) and 35 (CIDR6) days. At CIDR removal were administered PGF2 &#945;, ECP, eCG and US to measure the largest follicle (LF), and blood collection for P4 analysis. The TAI occurred 55 hours after device removal. The LF diameter was greater (p <0.01) in CIDR reused in cows. P4 concentration was lower in CIDR reused, but was higher than 1.5 ng / mL, and the device reused up to 5 times in cows and 6 times heifers did not affect pregnancy rate. The 7d-CIDR protocol allowed the reuse of CIDR up to 6 times keeping the same efficiency of CIDR new. In the experiment III the objective was to evaluate whether the application of eCG two days before the device removal increases the size of OF, CL and pregnancy rates. Six hundred and eighty-one suckling cows 40-60 days postpartum and 182 pubertal heifers were used. The animals were divided into two treatments with eCG application in fifth (5d-eCG) or seventh day (7d-eCG) of protocol. In d0, the animals received EB + CIDR and day 7 CIDR was removed and administered PGF2 and ECP. Ten days after AI, US was performed to measure the size of CL and blood collection for P4 analysis. The TAI occurred 55 hours after CIDR removal. The treatment d5 eCG increased (p < 0.01) OF. In cows, the concentration of P4 after AI was higher (p = 0.04) in 5d-eCG. In heifers, the CL diameter was higher in 5d-eCG. However, the 5d-eCG did not increase (p > 0.1) pregnancy rate. The strategy of eCG application in d5 was efficient to increase ovulatory follicle, but did not increase pregnancy rate

Orientadores: Sebastião Roberto Taboga, Fernanda Cristina Alcântara dos Santos / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-20T16:21:42Z (GMT). No. of bitstreams: 1 Zanatelli_Marianna_M.pdf: 26022421 bytes, checksum: 23b2b9c60198cc10c0b2a25abeb3f837 (MD5) Previous issue date: 2012 / Resumo: A próstata feminina é uma glândula funcionalmente ativa encontrada em diversas espécies de mamíferos, incluindo humanos e roedores. Em fêmeas adultas de gerbilos, a próstata apresenta localização parauretral, exibindo íntimo contato com a parede da uretra média. Esta glândula é homóloga à próstata ventral de roedores machos, sendo formada por um conjunto de ácinos e ductos inseridos em um estroma fibromuscular. O estudo da morfofisiologia prostática nas fases do ciclo estral tem demonstrado que a próstata feminina é influenciada pelas oscilações nos níveis séricos de estradiol e progesterona, com picos nas fases de estro e diestro II, respectivamente. Sendo assim, este trabalho teve como objetivo avaliar o efeito da administração combinada e prolongada de estradiol e progesterona sobre a próstata de fêmeas de gerbilo ovariectomizadas. A ovariectomia causou regressão glandular e diminuição da atividade secretora, aspectos sugeridos, entre outros, pela diminuição da massa prostática e a quase ausência de secreção glicoprotéica. Essas mudanças estão ligadas à supressão hormonal causada pela retirada dos ovários. A posterior reposição pelo estradiol e pela progesterona em associação mostrou uma grande recuperação da estrutura e fisiologia geral da próstata, evidenciada pelo aumento da altura do epitélio, da massa prostática e da atividade secretora. Os níveis hormonais aumentaram, justificando a recuperação da glândula, porém não atingiram o mesmo perfil observado no grupo controle. Também foram avaliadas as alterações na expressão de AR, ER?, ER? e no indicador de proliferação celular, PCNA, que mostraram maior imunorreatividade e maior número de células proliferativas no grupo tratado. A integridade da próstata não se relaciona apenas com os níveis de estrógeno e progesterona, mas também com o balanço cíclico entre esses hormônios no organismo feminino. Por fim, estudos sobre as ações do estrógeno e da progesterona na próstata podem abrir caminho para o desenvolvimento de tratamentos de importantes doenças prostáticas, as quais acometem tanto indivíduos do sexo masculino quanto do sexo feminino / Abstract: The female prostate is a gland functionally active found in several species of mammals, including humans and rodents. In adult female gerbils, the prostate presents paraurethral location, showing close contact with the wall of the median urethra. This gland is homologous to the ventral prostate of male rodents and it is formed by a set of acini and ducts embedded in a fibromuscular stroma. The study of prostatic morphophysiology in the estrous cycle phases has shown that the female prostate is influenced by fluctuations in serum of estradiol and progesterone, with peaks in estrous and diestrus II phases, respectively. Therefore, this study aimed to evaluate the effect of combined and prolonged administration of estradiol and progesterone on the prostate of ovariectomized female gerbil. Ovariectomy caused regression and decreased glandular secretory activity, aspects suggested by the shrinkage of the prostate and the almost absence of glycoprotein secretion. These changes are linked to hormonal supply caused by the ovaries removal. The subsequent replacement by estradiol and progesterone in combination showed a greater recovery of the structure and general physiology of the prostate, as evidenced by increased epithelial height, prostatic mass and secretory activity. The hormone levels increased, justifying the recovery of the gland, but did not achieve the same profile observed in the control group. We also evaluated the changes in the expression of AR, ER?, ER? and the cell proliferation marker, PCNA, which showed increased immunoreactivity and increased number of proliferating cells in the treated group. The integrity of the prostate is not only related to the levels of estrogen and progesterone, but also with the cyclical balance between these hormones in the female body. Finally, studies about the actions of estrogen and progesterone in prostate may be the starter for the development of treatments for important prostate diseases, which affect both males and females / Mestrado / Biologia Celular / Mestre em Biologia Celular e Estrutural

A gonadotrofina coriônica equina (eCG) tem sido utilizada em programas de sincronização para inseminação artificial em tempo fixo e normalmente promove o aumento do volume do corpo lúteo e a da produção de progesterona. Além disso, esta mesma gonadotrofina pode ser utilizada para superovulação. Desse modo, hipóteses relativas aos mecanismos pelos quais gonadotrofinas exógenas alteram as funções celulares nos corpos lúteos resultantes foram formuladas. Para testar tais hipóteses, 18 vacas (Bos indicus) foram divididas em grupos: controle (n=5), estimulado (n=6) e superovulado (n=7) e a ovulação das mesmas foi sincronizada usando um protocolo já estabelecido com dispositivo de progesterona. Os animais estimulados receberam 400 UI de eCG no dia de remoção do dispositivo de progesterona e os animais superovulados 4 dias antes. No dia 7 após injeção de GnRh, os animais foram abatidos para a coleta de CLL e sangue. Análises de peso e volume de CL, concentração de progesterona (P4), bem como da expressão gênica e proteica de fatores angiogênicos e de proteínas esteroidogênicas foram realizadas. Além disso, o transcriptoma foi analisado por microarranjo. Foi observado que o volume do CL foi maior nos animais do grupo estimulado (1177,37 ± 167,07 mm3) e ainda maior nos do superovulado (1495,18 ± 137,01 mm3) quando comparados ao grupo controle (830,33 ± 234,99 mm3; p = 0,03). A concentração média de progesterona por CL nos animais do grupo estimulado foi maior que nos animais do grupo controle (5,95 ± 0,17 vs 3,69 ± 0,72 ng/ml; p = 0,03) e que nos superovulados (4,11 ± 0.73; p = 0,01). Além disso, os tratamentos com eCG aumentaram a expressão do FGFR2 e também da STAR nos animais estimulados e superovulados (p < 0,05). Quanto aos resultados do microarranjo, no total 242 transcritos foram aumentados e 111 foram diminuídos nos animais estimulados e 111 foram aumentados e 113 diminuídos nos animais superovulados em relação aos animais controle (~1,5 vezes, p 0.05). Entre os genes diferencialmente expressos, muitos estavam envolvidos na síntese de lipídios e na produção de progesterona, tais como: PPARG, HMGCR, STAR, receptores de prolactina e folistatina. Estes achados demonstraram que os tratamentos com eCG modularam a expressão gênica diferencialmente, dependendo do tratamento, e que nossos dados contribuem para entender as vias relacionadas ao aumento do volume do CL e da produção de progesterona observada após os tratamentos. Em um segundo experimento, foi realizado análises da influência do FSH na expressão de VEGF no cultivo de células da granulosa. Neste experimento foi possível observar que o FSH aumentou a expressão gênica e proteica do VEGF, colaborando com a ideia de que as gonadotrofinas têm propriedades angiogênicas. / Equine chorionic gonadotropin (eCG) has been widely used in synchronization protocol to artificial insemination program and usually promote corpus luteum (CL) volume increases and stimulates progesterone production. Furthermore the same gonadotropin can be used to superovulation protocols. Thus, hypotheses concerning the mechanisms by which exogenous gonadotropins alter cellular functions in resulting corpora lutea were formulated. To test that hypothesis, 18 (Bos indicus) cows were divided into control (n=5), stimulated (n=6) and superovulated groups (n=7). Ovulation was synchronized using a progesterone device-based protocol. Stimulated animals received 400 IU of eCG of device removal and superovulated animals received 2000 IU of eCG 4 days prior. Corpora lutea (CLL) and blood samples were collected seven days after GnRH administration. Analyses of CL weight and volume, progesterone (P4) concentration, as well as the gene and protein expression of angiogenic and steroidogenic proteins were performed. Furthermore, the transcriptome was evaluated by microarray. The CL volume was higher in superovulated (1495.18 ± 137.01) than in stimulated (1177.37 ± 167.07) cows and higher in stimulated than in the control (830.33 ± 234.99) cows, and the P4 concentration per CL was higher in stimulated (5.95 ± 0.17 ng/ml) animals than in the control (3.69 ± 0.72 ng/ml) and superovulated (4.11 ± 0.73 ng/ml; P = 0.01) animals. Overall, 242 transcripts were up-regulated and 111 transcripts were downregulated in stimulated cows (P 0.05) and 111 were up-regulated and 113 down-regulated in superovulated cows in relation to the control (1.5 fold, P 0.05). Among the differentially expressed genes, many were involved in lipid biosynthesis and progesterone production, as PPARG, HMGCR, STAR, prolactin receptors and follistatin. In conclusion, eCG modulates gene expression differently depending on the treatment. Our data contribute to the understanding of the pathways involved in increased CL volume and progesterone levels observed after eCG treatment. In a second experiment, analyzes were performed about the influence of FSH on the expression of VEGF in the culture of granulosa cells. In this experiment it was observed that FSH increases the expression of the VEGF gene and protein, these finding collaborate with the idea that gonadotrophins have angiogenic properties.

Abstract The biosynthesis and metabolism of sex steroids are controlled by a series of steroidogenic enzymes. In the placenta and the breast, 3β-hydroxysteroid dehydrogenase type 1 (3β-HSD1) is essential for the synthesis of all steroid hormones by catalyzing pregnenolone to progesterone (P) or dehydroepiandrosterone (DHEA) to androstenedione (A-dione). P450 aromatase (P450arom) converts androgens to estrogens and is therefore critical for estrogen production. 17β-hydroxysteroid dehydrogenases (17HSDs) are a group of enzymes responsible for the interconversion between low-activity 17-ketosteroids and high-activity 17β-hydroxysteroids, thus acting as key enzymes modulating the biosynthesis and metabolism of both estrogens and androgens. In situ hybridization assays showed that 3β-HSD1, P450arom and 17HSD1, 2, 5 and 7 are expressed in early and mid-gestation placentas. Abundant expressions of 3β-HSD1, P450arom and 17HSD1 were seen in syncytiotrophoblast (ST) cells. Signals of these three enzymes were also detected in some column cytotrophoblast (CCT) cells. 17HSD2 and 5 were located in intravillous stromal (IS) cells, whereas 17HSD7 mRNA was present in all types of placental cells. This suggests that the human placenta produces not only P and estrogens, but also androgens. Moreover, the placenta possesses a function, by the action of 17HSD2, to protect the fetus and the maternal body from excessive sex steroid influence. In tubal pregnancy, P450arom and 17HSD1 were found in ST cells, implying an estrogen biosynthesis mechanism similar to that in normal intrauterine pregnancy. In both JEG-3 choriocarcinoma cell line and cultured normal human cytotrophoblast (CTB) cells, retinoic acids were shown to promote the enzyme activity as well as mRNA expression of P450arom and 17HSD1, and hence their action on the biosynthesis of E2. The mRNA expressions of 17HSD1, 2 and 5 in 794 breast carcinoma specimens were analyzed and correlated with ERα, ERβ, PR, Ki67, c-erbB2 and clinical parameters. 17HSD1, 2 and 5 were detected in epithelial cells in normal and malignant breast tissues. In breast cancer specimens, the positive cases for 17HSD1, 2 and 5 were 16%, 25% and 65%, respectively. 17HSD1 was found to be an independent prognostic marker of the progression of breast cancer.

It is the aim of this study to elucidate the influence of progesterone on body weight regulation in intact female rats. A study of the literature includes a description of the body weight regulation and the effects of ovarian hormones on it. The controlled-system approach tries to link behavioral and physiological factors altering energy balance. The experimental study is subdivided into food-intake - and food-selection studies, a locomotor activity study, a study eliciting a possible role of thermogenesis, and finally rat liver studies which consist of a gas chromatography analysis of hepatic fatty acids and an electron microscopy study examining the ultrastructure of hepatocytes. It can be concluded that the effect of progesterone treatment on the body weight of intact female rats depends on the route of administration. There is a significant increase in body weight after subcutaneous progesterone injections without changes in total caloric intake and nutrient selection habits, indicating the importance of energy expenditure. But changes in spontaneous activity make no contribution in the progesterone-induced energy storage. It is also concluded that peripherally located brown adipose tissue thermogenesis is not changed, without ruling out the effect of more centrally located thermogenic organs as the liver. In this organ, small but significant changes in the fatty acid profile occur during the subcutaneous progesterone treatment.

Sex differences exist in the functioning of the two brain corticosteroid receptor systems. Ovarian steroid replacement alters receptor mRNA expression, receptor binding capacities, and receptor affinity. The abundance of both mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) message can be reduced by estrogen. Progesterone is able to partially antagonize the action of estrogen and to induce MR transcription. The effect of estrogen on receptor binding capacity is more modest than its transcriptional actions. Estrogen decreases MR binding more reliably than it does GR. Progesterone has high affinity for the MR and can substantially reduce MR affinity for corticoids. Androgen apparently regulates corticoid receptor transcription but may not affect binding capacity. Estrogen and androgen are both more potent in regulating pituitary-adrenal function than would be suggested by their actions on receptor binding parameters.

Ciliary neurotrophic factor (CNTF) is produced by astrocytes and promotes neurogenesis and neuroprotection. Little is known about the role of CNTF in affective behavior. We investigated whether CNTF affects depressive- and anxiety-like behavior in adult mice as tested in the forced swim, sucrose preference and elevated-T maze tests. Female wild type CNTF+/+ mice more readily developed behavioral despair with increased immobility time and decreased latency to immobility in the forced swim test than male CNTF+/+ littermates. The lack of CNTF in CNTF-/- mice had an opposite effect on depressive-like behavior in female mice (reduced immobility time and increased sucrose preference) vs. male mice (increased immobility time). Female wildtype mice expressed more CNTF in the amygdala than male mice. Ovariectomy increased CNTF expression, as well as immobility time, which was significantly reduced in CNTF-/- mice, suggesting that CNTF mediates overiectomy-induced immobility time, possibly in the amygdala. Progesterone but not 17-β estradiol inhibited CNTF expression in cultured C6 astroglioma cells. Progesterone treatment also reduced CNTF expression in the amygdala and decreased immobility time in female CNTF+/+ but not in CNTF-/- mice. Castration did not alter CNTF expression in males nor their behavior. Lastly, there were no effects of CNTF on the elevated T-maze, a behavioral test of anxiety, suggesting that a different mechanism may underlie anxiety-like behavior. This study reveals a novel CNTF-mediated mechanism in stress-induced depressive-like behavior and points to opportunities for sex-specific treatments for depression, e.g. progesterone in females and CNTF-stimulating drugs in males.

The uterine endometrium undergoes cyclical phases of cell proliferation, cell differentiation, and menstruation under the influence of the ovarian hormones, estrogen and progesterone. Since the data necessary to create a classical kinetic model of these signaling pathways is lacking, we used a Boolean network approach that includes the influences of various growth factors and the differential expression of their receptors under the influence of estrogen and progesterone. Results show a gain in endometrial tissue and loss of tissue during menstruation that mirrors what can be expected over the course of a normal menstrual cycle in women, where the endometrium typically reaches a thickness of approximately 10 mm. We utilized an existing model of the normal menstrual cycle that was used to predict hormonal changes following administration of GnRH analogues. We adapted this model to provide the hormonal and ovarian compartments that would interact with our model of the endometrial cycle.