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Effects of the aromatase inhibitor fadrozole on plasma sex steroid secretion and ovulation rate in female coho salmon, Oncorhynchus kisutch, close to final maturation

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GENERAL AND COMPARATIVE ENDOCRINOLOGY 1999年第2期113卷 221-229页

作者： Afonso, LOB Iwama, GK Smith, J Donaldson, EM Fisheries & Oceans Canada W Vancouver Lab W Vancouver BC V7V 1N6 Canada Canadian Bacterial Dis Network Vancouver BC V6T 1Z4 Canada Dept Anim Sci Vancouver BC V6T 1Z4 Canada

Plasma levels of 17 beta-estradiol, 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17 alpha,20 beta-P), and testosterone were measured in adult female coho salmon in late vitellogenesis, approximately 1.5 months before spawning and just before and following intraperitoneal injection with the aromatase inhibitor (AI) Fadrozole. Injection at dosages of 0.1, 1.0, and 10.0 mg AI/kg body wt caused a significant drop in plasma 17 beta-estradiol levels relative to preinjection values within 3 or 6 h. Injection of 10 mg AI/kg body wt caused a significant increase in plasma 17 alpha-20 beta-P levels within 3 h. Ten days after injection 67% of the fish treated with 10 mg AI/kg body wt had ovulated in contrast with 0% in the group injected with 0.1 mg AI/kg body wt. The fertilization rate of the eggs varied between 96% in the control group and 85% in the groups injected with AI. We conclude that the shift from 17-beta-estradiol to 17 alpha,20 beta-P biosynthesis, which is characteristic of maturing Oncorhynchus sp., was advanced significantly by treatment with AI and that Fadrozole can be used as a tool to investigate periovulatory endocrine changes in salmon. (C) 1999 Academic Press.

关键词：芳香酶/药理学芳香酶抑制剂雌二醇/血液雌二醇/分泌雌激素拮抗剂/药理学法倔唑/药理学受精羟孕酮类/血液大麻哈鱼银/生理学卵巢/药物作用排卵放射免疫测定/兽医学随机分配睾酮/血液睾酮/分泌卵黄发生/药物作用动物女(雌)性男(雄)性

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Sublethal lead affects pituitary function of rainbow trout during exogenous vitellogenesis

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ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 2000年第1期38卷 46-51页

作者： Ruby, SM Hull, R Anderson, P Concordia Univ Dept Biol Ecotoxicol Lab Montreal PQ H3G 1M8 Canada

Sexually maturing female rainbow trout, Oncorhynchus mykiss, were exposed to 10 mu g/L of waterborne lead Pb(NO3)(2) for 12 days during endogenous vitellogenesis and 12 days during exogenous vitellogenesis. Lead had no significant effect on either gonadosomatic indices or mean maximum diameters of developing oocytes during early vitellogenesis. When females were exposed during exogenous vitellogenesis, however, both GSI and oocyte growth were significantly different from controls on day 12. Similarly GSI and oocyte growth was significantly reduced in lead-exposed fish. Atomic absorption spectroscopy measurements of lead levels in liver, ovaries, and blood tissues showed significant levels of lead in the blood. Lead did not accumulate in either the ovaries or the liver. Analysis of pituitary basophils during both endogenous and exogenous vitellogenesis and subsequent comparison with reproductive parameters in the ovaries indicated that GtH-basophils did not significantly increase in controls during endogenous vitellogenesis, and there was no significant change in GSI or ovarian growth in either controls or lead-exposed females. However during exogenous vitellogenesis, control basophils significantly increased over the 12-day experiment, but were not significantly different over 12 days in lead-exposed females. Both GSI and oocyte growth were significantly different from controls in lead-exposed females. The results suggest that naturally occurring changes in GTH-producing basophils during vitellogenesis alters GSI and oocyte growth in female rainbow trout exposed to lead during exogenous vitellogenesis, but not during endogenous vitellogenesis.

关键词：细胞计数/药物作用铅/血液铅/毒性硝酸盐类/血液硝酸盐类/毒性大麻哈鱼裂喉/生理学卵母细胞/药物作用卵母细胞/病理学器官测量/药物作用卵巢/化学卵巢/药物作用卵巢/病理学垂体/药物作用垂体/代谢垂体/病理学卵黄发生/药物作用水污染物化学性/血液水污染物化学性/毒性动物女(雌)性

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Evidence that acute stress inhibits ovarian steroidogenesis in rainbow trout in vivo, through the action of cortisol

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GENERAL AND COMPARATIVE ENDOCRINOLOGY 2000年第2期117卷 225-237页

作者： Pankhurst, NW Van der Kraak, G Univ Tasmania Sch Aquaculture Launceston Tas 7250 Australia Univ Guelph Dept Zool Guelph ON N1G 2W1 Canada

Sexually mature (preovulatory) rainbow trout exposed to confinement stress showed a transitory increase in plasma cortisol levels that was accompanied by a similarly brief depression in plasma testosterone (T) levels. Plasma levels of maturational gonadotropin (GtH) and 17 beta-estradiol (E(2)) were unaffected by stress. A similar pattern was displayed by fish exposed to stress in midvitellogenesis. Treatment of vitellogenic fish with exogenous cortisol resulted in significant increases in plasma cortisol at 1 and 3 h postinjection (p.i.). This was associated with significant depression of plasma T levels at 1 and 3 h p.i. and plasma E(2) levels at 3 and 6 h p.i. Plasma levels of GtH were unaffected by treatment with cortisol. Treatment of fish at an earlier stage of vitellogenesis with two different doses of cortisol resulted in very high elevations of plasma cortisol, but no effect on plasma levels of E(2) or GtH. In contrast, plasma T levels showed a stepwise decline over time. These results suggest that the inhibitory effects of stress on reproduction are mediated by cortisol and that the effect does not involve inhibition of GtH secretion and possibly acts at the level of GtH signal-transduction. (C) 2000 Academic Press.

关键词：雌二醇/血液氢化可的松/血液氢化可的松/药理学氢化可的松/生理学大麻哈鱼裂喉/代谢卵巢/代谢排卵/生理学约束身体的甾类/生物合成甾类/血液应激心理学/代谢睾酮/血液卵黄发生/药物作用卵黄发生/生理学动物女(雌)性

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Rainbow trout, Oncorhynchus mykiss, as a model for aromatase inhibition

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JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY 1999年第1-3期70卷 89-95页

作者： Shilling, AD Carlson, DB Williams, DE Oregon State Univ Dept Environm & Mol Toxicol Corvallis OR 97331 USA Oregon State Univ Marine Freshwater Biomed Sci Ctr Corvallis OR 97331 USA

The feasibility of utilizing rainbow trout, Oncorhynchus mykiss, as an alternative model for studying the inhibition of aromatase (CYP 19) was investigated. The suppression of estrogen-dependent tumors by aromatase inhibitors has been important in the treatment of breast cancer. Estrogens, estrogen precursors and xenoestrogens have been found to promote liver cancer in the trout model. A steroid, 4-hydroxy-4-androstene-3, 17-dione (4-OHA), and non-steroids, aminoglutethimide (AG) and Letrozole (CGS 20267), all of which are known aromatase inhibitors in rats and humans, were examined in vitro for activity in trout ovarian microsomes. Aromatase activity was quantified as the release of (H2O)-H-3 from the conversion of [H-3]-4-androstene-3,17-dione to 17 beta-estradiol and estrone. Trout ovarian microsomes exhibited activity between 39-60 finol mg(-1) min(-1) with a calculated V-max of 71.1 fmol mg(-1) min(-1) when incubated at 25 degrees C with 200 nM 4-androstene-3,17-dione (K-M = 435 nM). Significant inhibition by 4-OHA up to 80% was seen at 1.5 mu M. At 2000 mu M, AG decreased aromatase activity by up to 82%. Letrozole reduced aromatase activity a maximum of 90% in a dose-dependent manner, but the K-i (2.3 mu M) was 1000-fold higher than reported in human trials. Indole-3-carbinol and some of its derivatives, two DDE isomers and four flavones (except alpha-naphthoflavone) at 1000 mu M did not significantly inhibit aromatase in vitro. Letrozole and clotrimazole, fed to juvenile rainbow trout at doses up to 1000 ppm for 2 weeks, were not effective in suppressing dehydroepiandrosterone (DHEA) induced increases in vitellogenin and 17 beta-estradiol levels. These results document that trout aromatase is sensitive to inhibition in vitro by known inhibitors of the mammalian enzyme. The mechanism(s) for lack of inhibition in vivo is currently unknown and must be further investigated in order to develop a trout model for studying the role of aromatase in carcinogenesis. (C)

关键词：抗真菌药/药理学芳香酶抑制剂克霉唑/药理学去氢表雄酮/药理学酶抑制剂/药理学动力学微粒体/酶学模型生物学腈类/药理学裂喉大麻哈鱼/代谢卵巢/酶学三唑类/药理学卵黄发生/药物作用动物女(雌)性人类大鼠

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Transcriptional interference between glucocorticoid receptor and estradiol receptor mediates the inhibitory effect of cortisol on fish vitellogenesis

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BIOLOGY OF REPRODUCTION 2000年第6期62卷 1763-1771页

作者： Lethimonier, C Flouriot, G Valotaire, Y Kah, O Ducouret, B Univ Rennes 1 INRA UPRES A CNRS 6026 F-35042 Rennes France

In oviparous species, the synthesis of vitellogenin (Vg) fakes place in the liver according to a strictly estrogen-dependent mechanism that first involves an up-regulation of the estrogen receptor (ER) by its own ligand. However, reports from the literature indicate that in trout stress or cortisol may cause a reduction of cytosolic E2-binding sites in the liver and a decrease in plasma Vg levels. To investigate the mechanisms underlying these effects, in vivo and in vitro experiments were designed in rainbow trout (Oncorhynchus mykiss). The results demonstrate that cortisol implanted into maturing females caused a marked decrease of rainbow trout ER (rtER) and rainbow trout Vg (rtVg) mRNA levels in the liver. In vitro experiments on hepatocyte aggregates also showed that dexamethasone (Dex) caused a strong decrease in the basal and E2-stimulated rtER mRNA and to a lesser extent rtVg mRNA. These effects were specific as no other hormones were able to mimic the inhibitory action of Dex. A study of rtER mRNA stability indicated that the effects of glucocorticoids are likely to fake place at the transcriptional level. This was further indicated by transfection experiments in CHO-K-1 cells, which showed that rainbow trout glucocorticoid receptor (rtGR) strongly inhibited the Ea-stimulated transcriptional activity of the rtER promoter. Taken together, these results indicate that the rtGR exerts a transcriptional interference on the expression of the rtER that may explain some of the negative effects of stress or cortisol on vitellogenesis.

关键词：细胞培养的地塞米松/药理学药物植入物药物稳定性基因表达/药物作用糖皮质激素类/药理学氢化可的松/投药和剂量氢化可的松/药理学肝/代谢大麻哈鱼裂喉 RNA 信使/代谢受体雌二醇/遗传学受体糖皮质激素/遗传学转录遗传/药物作用卵黄发生/药物作用动物女(雌)性

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