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研究生:張力天
研究生(外文):Cicero Lee-Tian Chang
論文名稱:Ketoconazole對雄畜睪丸類固醇生合成作用之研究
論文名稱(外文):The Study of Ketoconazole on Testicular Steroidogenesis in Male Animal
指導教授:馮翰鵬
指導教授(外文):Hang-Poung Fung
學位類別:博士
校院名稱:國立中興大學
系所名稱:獸醫學系
學門:獸醫學門
學類:獸醫學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:94
中文關鍵詞:ketoconazole雄畜MA-10細胞睪丸
外文關鍵詞:ketoconazolemale animalMA-10 cellstestis
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摘 要
Ketoconazole (KCZ)為imidazole類的抗黴菌劑,為瞭解KCZ抑制類固醇內泌素生合成的作用,本實驗利用成年公犬及小鼠睪丸間質細胞瘤MA-10細胞研究KCZ減少雄性素生合成的可能機制。以每日每公斤30 mg KCZ單一口服劑量連續投予公犬七日及以每公斤30 mg KCZ單一口服劑量投予公犬,並分別檢測公犬於服用KCZ前後血清類固醇內泌素生成的變化及服藥後24小時內的血清睪固酮分泌狀況;另外以每公斤30 mg及10 mg KCZ單一口服劑量分別間隔投予對人類絨毛膜性腺激素刺激正常反應之公犬,以檢測公犬於不同劑量KCZ投予前後,以及在人類絨毛膜性腺激素刺激後的血清睪固酮濃度,結果顯示KCZ抑制公犬的助孕素轉換成睪固酮及氫基皮質酮,且呈現對公犬睪固酮分泌之暫時性抑制作用,而對公犬睪固酮分泌之作用具有顯著的劑量差異性 (P<0.05),而此顯著差異性未顯現於KCZ於公犬對人類絨毛膜性腺激素刺激反應下血清睪固酮生合成作用。此外亦利用小鼠睪丸間質細胞瘤MA-10細胞,研究KCZ在in vitro下對睪丸分泌助孕素及環單磷酸核腺之影響,結果指出KCZ抑制間質細胞之adenylate cyclase holoenzyme催化部分之作用。由以上的結果顯示KCZ除了經由選擇性抑制cytochrome P-450相關性酵素及競爭性佔據雄性素受納器外,亦可能藉阻斷adenylate cyclase的活性,來達到抑制睪丸分泌睪固酮的作用。

Summary
Ketoconazole (KCZ) is an imidazole antifungal agent. According to the inhibitory effect of KCZ on steroid hormones biosynthesis, our laboratory utilized the adult male dogs and MA-10 mouse Leydig tumor cells for investigating the possible mechanism of causing androgen deficiency by KCZ. The male dogs were orally administrated with 30 mg KCZ/ kg of body weight/day for a week for detecting the changes of serum steroid hormones production. A single oral dose of 30 mg KCZ/ kg of body weight was also administered to other male dogs and followed by 24-hour observation. Another male dogs with normal response to human chorionic gonadotropin (hCG) were orally administered with 10 mg KCZ/ kg of body weight and (30 mg KCZ /kg of body weight, respectively. Thereafter, the effects of different-dose KCZ on male dog’s testosterone production and its response to hCG stimulation were also investigated. The results indicated that KCZ inhibited the conversion from progesterone to testosterone and cortisol in male dogs. Meanwhile, KCZ exerted temporary inhibition on testosterone biosynthesis within 24 hours in male dogs. In addition, the significant difference between dosages on the effects of KCZ treatment on testosterone secretion in male dogs was observed. However, the effect of KCZ treatment on testosterone response to hCG stimulation between dosages was not significant. Moreover, the effects of KCZ on secretion of progesterone and cAMP in MA-10 cells were investigated in vitro. These data indicated that KCZ induced the inhibition of a catalytic component of adenylate cyclase holoenzyme in MA-10 cells. Excepting the selective inhibition of cytochrome P-450 enzymes and competitive binding of androgen receptors by KCZ, we concluded the block of adenylate cyclase activity by KCZ was another possible mechanism to inhibit testicular testosterone secretion.

目 次
中文摘要……………………………………………………………………1
英文摘………………………………………………………………………2
縮寫表………………………………………………………………………3
第一章 文獻探討………………………………………………………6
第一節 Ketoconazole的作用機制…………………………………6
第二節 Ketoconazole的藥理作用………………………………10
第三節 Ketoconazole抑制雄性素的生成………………………13
第四節 Ketoconazole抑制氫基皮質酮的生成…………………16
第五節 Ketoconazole的其他作用………………………………19
第六節 小鼠睪丸間質細胞瘤MA-10細胞…………………………22
第二章 材料與方法……………………………………………………23
第一節 實驗犬資料及小鼠間質細胞瘤MA-10細胞培養方法……23
第二節 Ketoconazole對公犬睪丸類固醇生合成作用之研究…24
實驗一 高劑量Ketoconazole對睪固酮及氫基皮質酮生合成
之研究……………………………………………24
實驗二 Ketoconazole對人類絨毛膜性腺激素刺激睪固酮
生合成之研究……………………………………26
實驗三 高劑量Ketoconazole對睪固酮分泌之影響……26
第三節 Ketoconazole對小鼠間質MA-10細胞助孕素及cAMP
生合成之研究……………………………………………27
第四節 統計分析…………………………………………………29
第三章 結果…………………………………………………………30
第一節 高劑量Ketoconazole對公犬睪固酮及氫基皮質酮生合成
之影響……………………………………………………30
第二節 Ketoconazole在公犬對人類絨毛膜性腺激素刺激睪固酮
生合成之影響……………………………………………31
第三節 高劑量Ketoconazole對公犬睪固酮分泌之影響………31
第四節 Ketoconazole對小鼠間質MA-10細胞助孕素及cAMP
生合成之影響……………………………………………32
第四章 討論……………………………………………………………48
附錄
附錄一 MA-10細胞生成助孕素相關的促進式化學冷光檢測圖…57
附錄二 發表文獻…………………………………………………58
參考文獻…………………………………………………………………81
圖 表 目 錄
表 次
Table 1. Serum Levels of Cholesterol before, during and after
Cessation of High-dose Ketoconazole Administration…35
Table 2. Serum Levels of Cortisol, Testosterone and
Progesterone before, during and after Cessation of
High-dose Ketoconazole Administration…………………36
Table 3. Spermatozoal Numbers before, during and after
Cessation of High-dose Ketoconazole Administration…37
Table 4. Basal and Post-hCG Stimulation Serum Testosterone
Levels in Male Dogs Given Different Doses of
Ketoconazole……………………………………………………38
Table 5. Effect of Ketoconazole and db-cAMP on Progesterone
Release in MA-10 Cells3……………………………………39
Table 6. Effect of Ketoconazole on Forskolin and Sodium
Fluoride Stimulated Progesterone and cAMP Release in
MA-10 Cells……………………………………………………40
圖 次
Fig. 1 Structure of Ketoconazole…………………………………41
Fig. 2 Impact of Ketoconazole of Steroidogenesis Pathways…42
Fig. 3 Changes of Plasma Testosterone Concentrations before and
after the Administration of Ketoconazole in Six Intact
Male Adult Dogs…………………………………………………43
Fig. 4 The Inhibitory Effect of Ketoconazole on Progesterone
Release in MA-10 Cells………………………………………44
Fig. 5 The Inhibitory Effect of Ketoconazole on Progesterone
Release in MA-10 Cells under LH Stimulation……………45
Fig. 6 The Inhibitory Effect of Ketoconazole on cAMP and
Progesterone Release in MA-10 Cells in the presence of
IBMX and LH………………………………………………………46
Fig. 7 Model of the Action of Ketoconazole on the Adenylate
Cyclase in MA-10 Cells………………………………………47

參 考 文 獻
Albertson BD, Frederick KL, Maronian NC, Feuillan P, Schorer S, Dunn JF, Loriaux DL. The effect of ketoconazole on steroidogenesis: I. Leydig cell enzyme activity in vitro. Res Commun Chem Pathol Pharmacol 61: 17-26, 1988.
Allen JM, Kerle DJ, Ware H, Doble A, Williams G, Bloom S. Combined treatment with ketoconazole and luteinizing hormone releasing hormone analogue: a novel approach to resistant progressive proatatic cancer. Br Med J 287: 1766, 1983.
Angeli A, Frairia R. Ketoconazole therapy in Cushing’s disease. Lancet 1: 821, 1985.
Ascoli M. Characterization of several clonal lines of cultured Leydig tumor cells:
gonadotropin receptors and steroidogenic responses. Endocrinology 108: 88-95,
1981.
Baroni A, Ruocco V, De Paolis P, Cicatiello L, Esumi H, Tufano MA. Ketoconazole inhibits lipopolysaccharide-induced activation of the nitric oxide synthase gene in the murine macrophage cell line J774. Arch Dermatol Res 291: 54-58, 1999.
Baxter JG, Brass C, Schentag JJ, Slaughter RL. Pharmacokinetics of ketoconazole administered intravenously to dogs and orally as tablet and solution to humans and dogs. J Pharm Sci 75: 443-447, 1986.
Best TR, Jenkins JK, Murphy FY, Nicks SA, Bussell KL, Vesely DL. Persistent adrenal insufficiency secondary to low-dose ketoconazole therapy. Am J Med 82: 676-680, 1987.
Bhasin S, Sikka S, Fielder T, Sod-Moriah U, Levine HB, Swerdloff RS, Rajfer J.
Hormonal effects of kctoconazole in vivo in the male rat: mechanism of action.
Endocrinology 118: 1229-1232, 1986.
Biswanath D, Plattner JJ, Bush EN, Jae H-S, Diaz G, Johnson ES, Perun TJ. LH- RH
antagonists: Design and synthesis of a novel series of peptidomimetics. J Med
Chem 32: 2036-2038, 1989.
Borelli D, Bran JL, Fuentes J. Ketoconazole, an oral antifungal: laboratory and
clinical assessment of imidazole drugs. Postgrad Med J 55: 657-661, 1979.
Borgers M, Van den Bossche H. The mode of action of antifungal drugs. In: Levine HB, ed. Ketoconazole in the management of fungal disease. New York, ADIS Press, 24-47, 1982.
Boscaro M, Sonino N, Rampazzo A, Menegus AM, Mantero F. ACTH response to corticotropin releasing hormone in Cushing’s disease before and after ketoconazole: in vivo and in vitro studies. Hor Metab Res Suppl 16: 60-62, 1987.
Bradbook ID, Gillies JC, Morrison PF, Robinson J, Rogers HJ, Spector RG. Effects of single and multiple doses of ketoconazole on adrenal function in normal subjects. Br J Clin Pharmacol 20: 163-165, 1985.
Brass C, Galgiani JN, Blaschke TF, DeFelice R, O’Reilly RA, Stevens DA. Disposition of ketoconazole, an oral antifungal, in humans. Antimicrob Agents Chemother 21: 151-158, 1982.
Brown MW, Maldonado AL, Meredith CCG, Speeg KV Jr. Effect of ketoconazole on hepatic oxidative drug metabolism. Clin Pharmacol Ther 37: 290-297, 1985.
Burrin JM, Yeo TH, Ashby MJ, Bloom SR. Effect of ketoconazole on adreno-
corticotrophic hormone secretion in vitro and in vivo. J Endocrinol 108: 37-41,
1986.
Buttke TM, Chapman SW. Inhibition by ketoconazole of mitogen-induced DNA
synthesis and cholesterol biosynthesis in lymphocytes. Antimicrob Agents Chemother 24: 478-485, 1983.
Carlson HE. Gynecomastia. N Engl J Med 303: 795-799, 1980.
Carlson JC, Sawada M, Boone DL, Stauffer JM. Stimulation of progesterone
secretion in dispersed cells of rat corpora lutea by antioxidants. Steroids 60:
272-276, 1995.
Carvalho D, Pignateli D, Resende C. Ketoconazole for hirsutism. Lancet 2: 560, 1985.
Chang CLT, Fung HP, Mao CL, Chan JPW, Chuang ST, Cheng FP. Effect of
ketoconazole treatment on testosterone response to human chorionic gonadotropin
stimulation in male dogs. Taiwan J Vet Med Anim Husb 69: 123-129, 1999.
Chaudhary LR, Stocco DM. Inhibition of hCG- and cAMP-stimulated progesterone production in MA-10 mouse Leydig cells by ketoconazole. Biochem Int 18: 251-262, 1989.
Chien RN, Yang LJ, Lin PY, Liaw YF. Hepatic injury during ketoconazole therapy in
patient with onychomycosis: a controlled cohort study. Hepatology 25: 103-107,
1997.
Cohen H, Benjamin J, Kaplan Z, Kotler M. Administration of high-dose
ketoconazole, an inhibitor of steroid synthesis, prevents posttraumatic anxiety in an
animal model. Eur Neuropsychopharmacology 10: 429-435, 2000.
Contreras P, Altieri E, Liberman C. Adrenal rest tumor of the liver causing Cushing’s
syndrome: treatment with ketoconazole preceding an apparent surgical cure. J Clin Endocrinol Metab 60: 21-28 ,1985.
Contreras P, Rojas A, Biagini L, Gonzáles P, Massardo T. Regression of metastatic adrenal carcinoma during palliative ketoconazole treatment. Lancet 2: 151-152, 1985.
Couch RM, Muller J, Perry YS, Winter JSD. Kinetic analysis of inhibition of human adrenal steroidogenesis by ketoconazole. J Clin Endocrinol Metab 65: 551-554, 1987.
Craven PC, Graybill JR, Jorgensen JG, Dismukes WE, Levine BE. High-dose ketoconazole for treatment of fungal infections of the central nervous system. Ann Intern Med 98: 160-167, 1983.
Cronin MJ, Evans WS, Rogol AD, Weiss AA, Thorner MO, Orth DN, Nicholson WE, Yasumoto T, Hewlett EL. Prokaryotic adenylate cyaclase toxin stimulates anterior pituitary cells in culture. Am J Physiol 251: 164-171, 1986.
Cronin MJ, Hewlett EL, Evans WS, Thorner MO, Rogol AD. Human pancreatic
tumor growth hormone (GH) releasing factor and cyclic adenosine 3’,5’-
monophosphate evoke GH release from anterior pituitary cells: The effects of
pertussis toxin, cholera toxin, forskolin, and cycloheximide. Endocrinology 114:
904-913, 1984.
Daneshmend TK, Warnock DW, Tuner A, Robert CJC. Pharmacokinetics of ketoconazole in normal subjects. J Antimicrob Chemother 8: 299-304, 1981.
De Coster R, Beerens D, Dom J, Willemsens G. Endocrinological effects of single daily ketoconazole administration in male beagle dogs. Acta Endocrinol (Copenh) 107: 275-281, 1984.
De Coster R, Caers I, Coene M-C, Amery W, Beerens D, Haelterman C. Effects of
high dose ketoconazole therapy on themain plasma testicular and adrenal steroids
in previously untreated prostatic cancer patients. Clin Endocrinol 24: 657-664,
1986.
De Coster R, Caers I, Haelterman C, Debroye M. Effect of a single administration of
ketoconazole on total and physiologically free plasma testosterone and 17β
-oestradiol levels in healthy male volunteers. Eur J Clin Pharmacol 29: 489-493,
1985.
DeFelice P, Johnson DG, Galgiani JN. Gynecomastia with keotconazole. Antimicrob Agents Chemother 19: 1073-1074,1981.
Denis L, Chaban M, Mahler C. Clinical applications of ketoconazole in prostatic
cancer. Prog Clin Biol Res 185A: 319-326, 1985.
Di Pietra AM, Cavrini V, Andrisano V, Gatti R. HPLC analysis of imidazole
antimycotic drugs in pharmaceutical formulations. J. Pharm Biomed Anal 10:
873-879, 1992.
Dixon D, Shadomy S, Shadomy HJ, Espinel-Ingroff A, Kerkering TM. Comparison of the in vitro antifungal activities of miconazole and a new imidazole R414,00. J Infect Dis 138: 245-248, 1978.
Duarte PA, Chow CC, Simmons F, Ruskin J. Fetal Hepatitis associated with ketoconazole therapy. Arch Intern Med 144: 1069-1070, 1984.
Dunbar M, Pyle RL, Boring JG, McCoy P. Treatment of canine blastomycosis with ketoconazole. JAVMA 182: 156-157, 1983.
Eil C. Ketoconazole binds to the human androgen receptor. Horm Metab Res 24: 367-370, 1992.
Engelhardt D, Dörr G, Jaspers Cc, Knorr D. Ketoconazole blocks cortisol secretion in man by inhibition of adrenal 11β-hydroxylase. Klin Wochenschr 63: 607-612, 1985.
Engelhardt D, Weber MM, Miksch T, Abedinpour F, Jaspers C. The influence of ketoconazole on human adrenal steroidogenesis: incubation studies with tissue slices. Clin Encocrinol 35: 163-168, 1991.
Engelhardt D, Mann K, Hörmann R, Braun S, Karl HJ. Ketoconazole inhibits cortisol secretion of an adrenal adenoma in vivo and in vitro. Klin Wochenschr 61: 373- 375, 1983.
Engelhardt D, Mann K, Hörmann R, Jüngst D, Braun S, Karl HJ. The influence of
ketoconazole on cortisol secretion in Cushing’s syndrome: in vivo and in vitro
studies of six patients. Acta Endocrinol (Suppl) (Copenh) 256: 281(Abstract), 1983.
Engelhardt D, Stutman HR, Marks MI. Interaction of ketoconazole with rifampin and
isoniazid. N Engl J Med 311: 1681-1683, 1984.
English HF, Santner SJ, Levine HB, Santeń RJ. Inhibition of testosterone production with ketoconazole alone and in combination with a gonadotropin releasing hormone analogue in the rat. Cancer Res 46: 38-42, 1986.
Erneux C, van Sande J, Miot F, Cochaux P, Decoster C, Dumont JE. A mechanism in
the control of intracellular cAMP level: The activation of a calmodulin-sensitive
phosphodiesterase by a rise of intracellular free calcium. Mol Cell Endocrinol 43:
123-134, 1985.
Fenner WR. Treatment of central nervous system infection in small animals. J Am
Vet Med Assoc 185: 1176-1180, 1984.
Gal M, Barr I, Mrs. Lior O, Tadmor O, Orly J, Diamant YZ. Effect of ketoconazole
on steroidogenic human granulosa-luteal cells in culture. Eur J Obstet Gynecol
Reprod Biol 39: 209-214, 1991.
Gal M, Eldar-Geva T, Margalioth EJ, Barr I, Orly J, Diamant YZ. Attenuation of
ovarian response by low-dose ketoconazole during superovulation in patients
with polycystic ovary syndrome. Fertil Steril 72: 26-31,1999.
Glass AR. Ketoconazole-induced stimulation of gonadotropin output in men: basis for
a potential test of gonadotropin reserve. J Clin Endocrinol Metab 63: 1121-1125, 1986.
Glass AR, Eil C. Ketoconazole-induced reduction in serum 1,25-dihydroxy-vitamin D. J Clin Endocrinol Metab 63: 766-769,1986.
Graybill JR, Drutz DJ. Ketoconazole: a major innovation for treatment of fungal disease. Ann Intern Med 93: 921-923,1980.
Gross DS, Boyden TW, Pamenter RW, Johnson DG, Stevens DA, Galgiani JN.
Ketoconazole inhibition of testicular secretion of testosterone and displacement of
steroid hormones from serum transport proteins. Antimicrob Agents Chemother 23:
207-212, 1983.
Harvey CE. Therapeutic strategies involving antimicrobial treatment of the upper
respiratory tract in small animals. J Am Vet Med Assoc 185:1159-1161, 1984.
Heel RC, Brogden RN, Carmine A, Morley PA, Speight TM, Avery GS. Ketoconazole: a review of its therapeutic efficacy in superficial and systemic fungal infections. Drugs 23: 1-36, 1982.
Henry HL. Effect of ketoconazole and miconazole on 25-hydroxy vitamin D3 metabolism by cultured chick kidney cells. J Steroid Biochem 23: 991-994,1985.
Heyns W, Drochmans A, van der Schueren E, Willemsens G. Endocrine effects of
high-dose ketoconazole therapy in advanced prostatic cancer. Acta Endocrinol
(Copenh) 110: 276-283, 1984.
Higashi Y, Masako O, Keiko S, Hiroshi I. Ketoconazole as a possible universal inhibitor of cytochrome P-450 dependent enzymes: its mode of inhibition. Endocrinol Japan 34: 105-115, 1987.
Hoffman DW, Jones-King KL, Ravaris CL, Edkins RD. Electrochemical detection for
high-performance liquid chromatography of ketoconazole in plasma and saliva.
Anal Biochem 172: 495-498, 1988.
Holland FJ, Fishman L, Bailey JD, Fazekas ATA. Ketoconazole in the management of
precocious puberty not responsive to LHRH-analogue therapy. N Engl J Med 312:
1023-1028, 1985.
Iranmanesh A, Ovetsky RM, Lizarralde G, Schleupner CJ. Effect of ketoconazole on
the 11-hydroxylation step of adrenal steroidogenesis. South Med J 80: 725-728,
1987.
Irsy G, Koranyi L. Neuroendocrinological effects of ketoconazole in rats. Acta Endocrinol (Copenh) 122: 409-413, 1990.
Jack G. Nonsurgical treatment of prostatic hyperplasia. Cancer Suppl 70: 339-344,
1992.
Jorgensen JH, Alexander GA, Graybill JR, Drutz DJ. Sensitive bioassay for ketoconazole in serum and cerebrospinal fluid. Antimicrob Agents Chemother 20: 59-62, 1981.
Kan PB, Hirst MA, Feldman D. Inhibition of steroidogenic cytochrome P-450
enzymes in rat testis by ketoconazole and related imidazole anti-fungal drugs. J
Steroid Biochem 23: 1023-1029, 1985.
Kowal J. The effect of ketoconazole steroidogenesis in cultured mouse adrenal cortex
tumor cells. Endocrinology 112: 1541-1543, 1983.
Kraemer FB, Pont A. Inhibition of cholesterol synthesis by ketoconazole AM J Med
80: 616-622, 1986.
Lacoste D, St-Arnaud R, Caron S, Belanger A, Labrie F. J. The rise in testicular
androgens during the first days of treatment with an LHRH agonist in the dog can be blocked by aminoglutethimide or ketoconazole.Steroid Biochem 31: 963- 970, 1988.
Lake-Bakaar G, Scherer PJ, Sherlock S. Hepatic reactions associated with ketoconazole in the United Kingdom. Br Med J 294: 419-422,1987.
Legendre AM, Selcer BA, Edwards DF. Treatment of candida blastomycosis with
amphotericin B and ketoconazole. J Am Vet Med Assoc 184: 1249-1254, 1984.
Lewis JH, Zimmerman HJ, Benson GD, Ishak KG. Hepatic injury associated with ketoconazole therapy: analysis of 33 cases. Gastroenterology 86: 503-513, 1984.
Loli P, Berselli ME, Tagalaferri M. Use of ketoconazole in the treatment of Cushing’s syndrome. J Clin Endocrinol Metab 63: 1365-1371,1986.
Loose DS, Kan PB, Hirst MA, Marcus RA, Feldman D. Ketoconazole blocks adrenal steroidogenesis by inhibiting cytochrome P450-dependent enzymes. J Clin Invest 71: 1495-1499, 1983.
Loose DS, Stover EP, Feldman D. Ketoconazole binds to glucocorticoid receptors and exhibits glucoccorticoid antagonist activity in cultured cells. J Clin Invest 72; 404-408, 1983.
Macnair AL, Gascoigne E, Heap J, Schuermans V, Symoens J. Hepatitis and
ketoconazole therapy. Br Med J 283: 1058, 1981.
Maher C. Ketoconazole and liarozole in the treatment of advanced prostatic cancer cancer. Cancer Suppl 71: 1068-1073, 1993.
Malozowski S, Mericq V, Cassorla F. Effects of ketoconazole on rat ovarian steroidogenic enzymatic activities. Res Commun Chem Pathol Pharmacol 52: 403-406, 1986.
Mannisto PT, Mantyla R, Mykanea S. Impairing effect of food in ketoconazole
absorption. Antimicrob Agents Chemother 21: 730-733, 1982.
McCance DR, Ritchie CM, Sheridan B, Atkinson AB. Acute hypoadrenalism and
hepatotoxicity after treatment with ketoconazole. Lancet 1: 573, 1987.
Medleau L, Chalmers SA. Resolution of generalized dermatophytosis without
treatment in dogs.JAVMA 201: 1891-1892, 1992.
Mosca P, Bonazzi P, Novelli G, Jezequel AM, Orlandi F. In vivo and in vitro inhibition of hepatic microsomal drug metabolism by ketoconazole. Br J Exp Pathol 66: 737-742, 1985.
Nagai K, Miyamori I, Ikeda M. Effect of ketoconazole (an imidazole antimycotic agent) and other inhibitors of steroidogenesis on cytochrome P450-catalyzed reactions. J Steroid Biochem 24: 321-323, 1986.
Nashan D, Knuth UA, Weidinger G, Nieschlag E. The antimycotic drug terbinafine in contrast to ketoconazole lacks acute effects on the pituitary-testicular function of healthy men: a placebo-controlled double-blind trial. Acta Endocrinol (Copenh) 120: 677-681, 1989.
Ng TKC, Chan RCY, Adeyemi-Doro FAB, Cheung SW, Cheng AFB. Rapid high
performance liquid chromatography assay for antifungal agents in human sera. J
Antimicrob Chemother 37: 465-472,1996.
Oelkers W, Bähr V, Hensen J, Pickartz H. Primary adrenocortical micronodular
adenomatosis causing Cushing’s syndrome: effects of ketoconazole on steroid
production and in vitro performance of adrenal cells. Acta Endocrinol (Copenh)
113: 370-377, 1986.
Pascucci VL, Bennett J, Narang PK, Chatterji DC. Quantitation of ketoconazole in
biological fluids using high-performance liquid chromatography. J Pharm Sci 72: 1467-1469, 1983.
Pilans PI, Cowan P, Whitelaw D. Hyponatraemia and confusion in a patient taking ketoconazole. Lancet 1: 821-822, 1985.
Pont A, Goldman ES, Sugar AM, Siiteri PK, Stevens DA. Ketoconazole-induced
increase in estraiol-testosterone ratio: probable explanation for gynecomastia. Arch
Intern Med 145: 1429-1431, 1985.
Pont A, Graybill JR, Craven PC, Galgiani JN, Dismukes WE, Reitz RE, Stevens, DA.
High-dose ketoconazole therapy and adrenal and testicular function in humans.
Arch Intern Med 144: 2150-2153, 1984a.
Pont A, Trachtenberg J. Hormonal changes in patientson chronic high dose ketoconazole therapy. Clin Res 32:271A (Abstract), 1984b.
Pont A, Williams PL, Azhar S, Reitz RE, Bochra C, Smith ER, Stevens DA. Ketoconazole blocks testosterone synthesis. Arch Intern Med 142: 2137-2140, 1982a.
Pont A, Williams PL, Loose DS, Feldman D, Reitz RE, Bochra C, Stevens DA.
Ketoconazole blocks adrenal steroid synthesis. Annals Intern Med 97: 370-372,
1982b.
Rajfer J, Sikka SC, Rivera F, Handelsman DJ. Mechanism of inhibition of human
testicular steroidogenesis by oral ketoconazole. J Clin Endocrinol Metab 63:
1193-1198, 1986.
Rajfer J, Sikka SC, Xie HW, Swerdloff RS. Effect of in vitro ketoconazole on steroid
production in rat testis. Steroids 46: 867-881, 1985.
Reina LJ, Leal-Cerro A, Garcia J, Garcia-Luna PP, Astorga R, Bernal G. In vitro
effects of ketoconazole on corticotrope cell morphology and ACTH secretion of
two pituitary adenomas removed from patients with Nelson’s syndrome. Acta
Endocrinol (Copenh) 121:185-190,1989.
Rijnberk A. Ovary, testis. In: Rijnberk A, ed. Clinical Endocrinology of Dogs and Cats. Kluwer Academic Publishers, Dordrecht, Nertherlands, 210-211, 1996.
Riley CM. Determination of ketoconazole in the plasma, liver, lung and adrenal of the
rat by high-performance liquid chromatography. J Chromatogr 377: 287-294, 1986.
Rober JC, Carr DC. Prostate cancer: current and evolving strategies. AMJ Health-Syst Pharm 53: 381-396, 1996.
Rodriguez RJ, Jr. Acosta D. Comparison of ketoconazole- and fluconazole- induced
hepatotoxicity in a primary culture system of rat hepatocytes. Toxicology 96:
83-92, 1995.
Root AW, Zamanillo J, Duckett G, Sweetland M. Gonadotropin-independent isosexual precocity in a boy with tuberous sclerosis: effect of ketoconazole. J Pediatr 109: 1012-1015, 1986.
Rotstein DM, Kertesz DJ, Walker KAM, Swinney DC. Stereoisomers of
ketoconazole: preparation and biological activity. J Med Chem 35: 2818-2825,
1992.
Saez JM. Leydig cells: endocrine, paracrine, and autocrine regulation. Endocr Rev 15:
574-626, 1994.
Santen RJ, Van den Bossche H, Symoens J, Brugmans J, De Coster R. Site of action of low dose ketoconazole on androgen biosynthesis in men. J Clin Endocrinol Metab 57: 732-736, 1983.
Schürmeyer Th, Nieschlag E. Effect of ketoconazole and other imidazole fungicides on testosterone biosynthesis. Acta Endocrinol (Copenh) 105: 275-280, 1984.
Sharp NJH, Sullivan M. Use of ketoconazole in the treatment of canine nasal aspergillosis. JAVMA 194: 783-786, 1989.
Sheets JJ, Mason JI. Ketoconazole: a potent inhibitor of cytochrome P450-dependent drug metabolism in rat liver. Drug Metab Dispos 12: 603-606, 1984.
Shepherd FA, Hoffert B, Evans WK, Emery G, Trachtenberg J. Ketoconazole: use in
the treatment of ectopic adrenocorticotropic hormone production and Cushing’s
syndrome in small-cell lung cancer. Arch Intern Med 145: 863-864, 1985.
Sikka SC, Swerdloff RS, Rajfer J. In vitro inhibition of testosterone biosynthesis
by ketoconazole. Endocrinology 116: 1920-1925, 1985.
Sonino N. The use of ketoconazole as an inhibitor of steroid production. N Engl J
Med 24: 812-818, 1987.
Sonino N, Boscaro M, Merola G, Mantero F. Prolonged treatment of Cushing’s
disease by ketoconazole. J Clin Endocrinol Metab 61: 718-722, 1985.
Stalla GK, Stalla J, Huber M, Loeffler J-P, Höllt V, von Werder K, Müller OA.
Ketoconazole inhibits corticotropic cell function in vitro. Endocrinology 122:
618-623, 1988.
Stalla GK, Stalla J, Loeffler JP, von Werder K, Müller OA. Pharmacological
modulation of CRH-stimulated ACTH secretion by ketoconazole. Horm Metab Res Suppl 16: 31-36, 1987.
Stalla GK, Stalla J, von Werder K, Müller OA, Gerzer R, Höllt V, Jakobs KH. Nitroimidazole derivatives inhibit anterior pituitary cell function apparently by a direct effect on the catalytic subunit of the adenylate cyclase holoenzyme. Endocrinology 125: 699-706, 1989.
Svec F. Differences in the interaction of RU 486 and ketoconazole with the second
binding site of the glucocorticoid receptor. Endocrinology 123: 1902-1906, 1988.
Swezey SF, Giacomini KM, Abang A, Brass C, Stevens DA, Blaschke TF. Measurement of ketoconazole, a new antifungal agent, by high-performance
liquid chromatography. J Chromatogr 277: 510-515, 1982.
Thienpont D, Van Cutsem J, Van Gerven F, Heeres J, Janssen PAJ. Ketoconazole — a new broad spectrum orally active antimycotic. Experientia 35: 606-607, 1979.
Trachtenberg J. Ketoconazole therapy in advanced prostatic cancer. J Urol 132: 61-63,
1984.
Trachtenberg J, Halpern N, Pont A. Ketoconazole: a novel and rapid treatment for
advanced prostatic cancer. J Urol 130: 152-153, 1983.
Trachtenberg J, Pont A. Ketoconazole therapy for advanced prostate cancer. Lancet 2: 433-435, 1984.
Thakore JH, Dinan TG. Cortisol synthesis inhibition: a new treatment strategy for
the clinical and endocrine manifestations of depression. Biol Psychiatry 37: 364-
368, 1995.
Trump DL, Havlin KH, Messing EM, Cummings KB, Lange PH, Jordan VC. High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects. J Clin Oncol 7: 1093-1098, 1989.
Tucker WS Jr, Snell BB, Island DP, Gregg CR. Reversible adrenal insufficiency
induced by ketoconazole. JAVMA 253: 2413-2414, 1985.
Turner CA, Turner A, Warnock DW. High performance liquid chromatographic
determination of ketoconazolle in human serum. J Antimicro Chemottherr 18:
757-763, 1986.
Van den Bossche H, Lauwers W, Willemsens G, Cools W. Ketoconazole an inhibitor
of the cytochrome P-450 dependent testosterone biosynthesis. Prog Clin Biol Res
185A: 187-196, 1985a.
Van den Bossche H, Willemsens G, Cobls W. In vitro and in vivo effects of the
antimycotic drug ketoconazole on sterol synthesis. Antimicrob Agents Chemother
17: 922-928, 1980.
Van den Bossche H, Willemsens G, Cobls W, Bellens D. Molecular basis for ketoconazole’s antifungal and anti-androgen activities. J Steroid Biochem 23(Suppl): 36S (Abstract), 1985b.
van der Meer JWM, Keuning JJ, Scheijgrond HW, Heykants J, Van Cutsem J,
Brugmans J. The influence of gastric acidity on the bioavailability of
ketoconazole. J Antimicrob Chemother 6: 552-554, 1980.
van Dijke CPH, Beerman FFR, Haverkamp HC. Anaphylactic reactions to ketoconazole. Br Med J 287: 1673, 1983.
Van Tyle JH. Ketoconazole: mechanism of action, spectrum of activity, pharmacokinetics, drug interactions, adverse reactions and therapeutic use.
Pharmacotherapy 4: 343-373, 1984.
Vawda AI, Davies AG. An investigation into the effects of ketoconazole on testicular function in Wistar rats. Acta Endocrinol (Copenh) 111: 246-251, 1986.
White MC, Kendall-Taylor P. Adrenal hypofunction in patients taking ketoconazole. Lancet 1: 44-45, 1985.
Wilkinson CF, Fetnarski K, Cantwell GP, Di Carlo FJ. Structure-activity relationships in the effects of 1-alkylimidazoles on microsomal oxidation in vitro and in vivo. Biochem Pharmacol 23: 2377-2386, 1974.
Willard MD, Nachreiner R, McDonald R, Roudebush P. Ketoconazole-induced changes in selected canine hormone concentrations. Am J Vet Res 47: 2504-2509, 1986.
Williams G. Ketoconazole for prostate cancer. Lancet 2: 696, 1984.
Wolkowitz OM, Reus VI, Chan T, Manfredi F, Raum W, Johnson R, Canick J. Antiglucocorticoid treatment of depression: double-blind ketoconazole. Biol Psychiatry 45: 1070-1074,1999.
Yuen KH, Peh KK. Simple high-performance liquid chromatographic method for determination of ketoconazole in human plasma. J Chromatogr 715: 436-440,1998.

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