Castration and testosterone replacement therapy served as a model to assess anabolic activity in the rat. The present study was undertaken to examine more closely whether changes in cellular anabolic activity are reflected in subsequent alterations of urinary N1 -acetylspermidine excretion. A sensitive fluorometric assay was employed which utilized the dansylation reaction . The dansylated derivatives were quantitated by normal phase high pressure liquid chromatography. This assay system exhibited a range of linearity from 0.1 to 10 nanomoles which encompassed the physiological variability observed during analysis of urinary N1-acetyl spermidine. The normal level of N1-acetylspermidine excreted in rat urine was found to be 803.1 ± 208.9 nanomoles per day (mean ± 1 S.D.). In addition both N8-acetylspermidine and acetyl putrescine were detected, but not quantitated. Due to the high variability of the polyamine excretion, no statistically significant difference could be detected between castrated animals, castrated animals receiving testosterone, and sham operated animals. Still some trends were noted which were in agreement with the hypothesis that urinary excretion of polyamines may reflect the anabolic state of the animal. Further studies will be required to determine whether or not a correlation between anabolic activity and urinary excretion of acetylated polyamines exists.

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This essay analyzes Esther Greenwood’s identity crisis, mental illness, and recovery in Sylvia Plath’s novel The Bell Jar (1963) from a feminist psychoanalytic perspective. The purpose is to understand the cultural and psychological mechanisms behind the main character’s situation. Esther is a talented and hardworking student who dreams of a literary career in 1950’s America. At the age of nineteen, events and realizations launch Esther into an identity crisis that leads to severe depression. Why she falls ill, and the nature of her illness and recovery, are up for interpretation. The thesis of this essay is that Esther Greenwood’s identity crisis, mental illness, and recovery can be explained using a feminist interpretation of Freud’s theories of hysteria and melancholia, and the development of the differences between the sexes, which includes the Freudian concepts of castration, bisexuality, and the Oedipus complex.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13517号 / 論医博第2267号 / 新制||医||1061(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 遊佐 宏介, 教授 戸井 雅和, 教授 小川 誠司 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Yes / The aldo-keto reductase 1C3 (AKR1C3) enzyme is considered an attractive target in Castration Resistant Prostate Cancer (CRPC) because of its role in the biosynthesis of androgens. Flufenamic acid, a non-selective AKR1C3 inhibitor, has previously been subjected to bioisosteric modulation to give rise to a series of compounds with the hydroxytriazole core. In this work, the hit compound of the previous series has been modulated further, and new, more potent, and selective derivatives have been obtained. The poor solubility of the most active compound (cpd 5) has been improved by substituting the triazole core with an isoxazole heteronucleous, with similar enzymatic activity being retained. Potent AKR1C3 inhibition is translated into antiproliferative effects against the 22RV1 CRPC cellular model, and the in-silico design, synthesis and biological activity of new compounds is described herein. Compounds have also been assayed in combination with two approved antitumor drugs, abiraterone and enzalutamide. / This research was financially supported by the University of Turin (Ricerca Locale grants BOSD_RILO_20_01, LOLM_RILO_21_01, PIPA_RILO_20_01 and PIPA_RILO_21_01), Fondazione Cassa di Risparmio di Torino (Grant BOSD_CRT_17_2) and TUBITAK (The Scientific and Technological Research Council of Turkey-2219 program).

The 12th and 13th centuries were period of heightened anxiety about the male body, its sexuality, and the definition of "manhood." Based on widening knowledge of human anatomy and masculinity, philosophers posed the question whether a eunuch could still be considered "male" if he lacked the sexual organs that identified him as a man. This debate then spread within the confines of the religious thought, as clerics discussed how the Church should treat eunuchs (legally and spiritually). The following thesis investigates medieval views on "manhood" and focuses on the status of eunuchs within the ecclesiastical system. Peter Abelard (1079- 1142), a philosopher who was made eunuch, will be used as a window to the treatment of eunuchs by the Church. The thesis argues that although the Church did not approve of castration, there were no specific canon laws which ostracized or damned eunuchs. Furthermore, this thesis shows that because Abelard had successfully consummated his marriage, there was no mandate for Abelard to renounce his relationship with his wife Heloise after being castrated. Finally, this thesis charts Abelard's opinions on his own castration, beginning with his interpretation of the Mosaic Law as evidence for God's abhorrence of eunuchs and ending with his belief that his castration was a divinely granted remedy that allowed him to focus on excelling as a philosopher and theologian.

Nous avons étudié la mêtabolisation des C-19 stéroïdes tritiês: androstenedione (A4-dione), déhydroépiandrostérone (DHEA) et androst-5-ene-3B, 17B-diol (A⁵-diol) lors d’une incubation de 3 heures à 37°C avec des homogénats de tumeurs mammaires murines Shionogi androgêno-dépendantes et androgêno-indêpendantes. L’analyse et la mesure des métabolites par chromatographie sur colonnes de Séphadex LH-20 puis chromatographie sur couche mince avec gel de silice a prouvé l’existence dans les 2 types de tumeurs d’enzymes (17B-déhydrogénase, 3B-déhydrogénase A⁵, A4-isomêrase et 5a-ré- ductase) qui assurent la conversion des androgènes surrénaliens en androgènes actifs, principalement T (testostérone) et A (androsté- rone) à partir du A4-dione, 3a-diol (androstane-3a, 17B-diol) à partir du A⁵-diol, androstérone à partir du DHEA. Les tumeurs indépendantes présentaient une activité 5a-réductase significativement plus élevée (p < 0.01) que les tumeurs dépendantes alors que ces dernières seulement ont conduit à la formation de produits identifiés comme catêcholestrogènes, à partir du A5-diol presque exclusivement. Par ailleurs, nous avons mesuré par radioimmunoétalonnage les niveaux plasmatiques de P (progestérone), DHEA, A⁵-diol, A4, T, DHT (dihydrotestostérone), 3a-diol, 3B-diol (androstaene-3B, 17B- diol) chez des souris mâles DD/Sio intactes ou castrées et dans des tumeurs qui se sont développées chez des animaux intacts et castrés, à la suite de l'inoculation de 106 cellules de la même tumeur androgéno-dêpendante Shionogi SC 115. Il est apparu que si 2 jours après castration, la testostérone et le A4-dione avaient pratiquement disparu de la circulation, des précurseurs (A⁵-diol) ou des androgènes puissamment actifs (DHT, 3a-diol) y étaient encore présents (plus de 30%). De plus, alors que les concentrations tumorales de testostérone et de A4-dione étaient réduites de plus de 90% chez les castrés, celles du A⁵-diol ne l'étaient que de 70%, celle du DHEA que de 30%. Les concentrations de 3a-diol et de DHT chez les castrés (60% et 7% des concentrations mesurées chez les normaux) étaient suffisantes pour induire une réponse androgénique dans ces tumeurs. De fortes corrélations enfin ont été trouvé liens et dans ces mêmes tumeurs entre des précurseurs surrénaliens et des androgènes actifs (DHEA et 3a-diol, r = 0.97, par exemple). Ces résultats viennent étayer une hypothèse que nous proposons dans cette thèse d'adaptation de tumeurs androgéno-dépendantes à "privatif” dépourvu d'androgènes testiculaires. Cette consisterait en un démasquage ou une activation d'enzymes qui convertissent in situ des précurseurs stéroïdiens périphériques (C-19 stéroïdes surrénaliens en particulier) en des androgènes actifs. / Montréal Trigonix inc. 2018