The Mechanism of Cyclosporineʼs Action in the Inhibition of Testosterone Biosynthesis by Rat Leydig Cells in Vitro1,2

Seethalakshmi, L.; Flores, Cristián; Malhotra, Ravindra K.; Pallias, J. D.; Tharakan, D.; Khauli, Raja B.; Menon, Mangaladevi

doi:10.1097/00007890-199201000-00037

Cited by 20 publications

(15 citation statements)

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“…Kinetic studies of 3␤-HSD and 17␤-HSD3 activities showed that the K m (app) was 0.67 M for 3␤-HSD and 2.67 M for 17␤-HSD3, which are values comparable to those in previous reports [13]. Inhibition by PFOA of either 3␤-HSD or 17␤-HSD3 was competitive for the substrate.…”

Section: Discussionsupporting

confidence: 85%

“…In brief, 3␤-HSD activity assay tubes contained 1 M PREG and 40,000 dpm [ 3 H] PREG (PREG was dissolved in ethanol, the final concentration of ethanol in an assay tube was 0.2%). The substrate concentration was selected based on the interstitial fluid steroid levels [13]. The 45 min reactions were initiated by addition of 40 g rat testis microsome proteins with 0.2 mM NAD + in presence of different concentrations of PFOA to determine half-maximal inhibitory concentration (IC 50 ).…”

Section: ˇ-Hsd Assaymentioning

confidence: 99%

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Inhibition of 3β- and 17β-hydroxysteroid dehydrogenase activities in rat Leydig cells by perfluorooctane acid

Zhao¹,

Chu²,

Hardy³

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Discussionsupporting

confidence: 85%

Section: ˇ-Hsd Assaymentioning

confidence: 99%

Inhibition of 3β- and 17β-hydroxysteroid dehydrogenase activities in rat Leydig cells by perfluorooctane acid

Zhao¹,

Chu²,

Hardy³

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

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“…It has been reported that exposure to CsA in vitro did not inhibit basal secretion of T but diminished T release after hCG stimulation (34), although another author did not find the latter effect (33). It has been reported that exposure to CsA in vitro did not inhibit basal secretion of T but diminished T release after hCG stimulation (34), although another author did not find the latter effect (33).…”

Section: Discussionmentioning

confidence: 99%

Modulation of the Testicular Steroidogenic Pathway by Cyclosporin A in Adult Rats Pretreated with Diethylstilbestrol

Villanúa¹,

Amador²,

Bartke

et al. 1997

Experimental Biology and Medicine

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Treatment of male Fischer-344 rats with diethylstilbestrol (DES) induces hyperprolactinemia and alterations in testicular steroidogenesis. Cyclosporin A (CsA), an immunosuppressive drug, is believed to act by opposing the effects of prolactin (PRL) and was reported to influence testicular function. We have examined the effect of CsA on gonadal function in rats pre-treated with DES. Male rats were implanted with DES-containing silastic capsules. After 19 weeks, the capsules were removed, and, starting 2.5 weeks later, rats were treated for 1 week with CsA. At sacrifice, plasma and testes were collected. Testis fragments were incubated with or without 12.5 mlU of human chorionic gonadotropin (hCG)/ml at 32 degrees C for 4 hr. As expected, plasma PRL levels were increased in DES exposed rats, while testicular, seminal vesicle, and prostate weights were reduced. Cyclosporin A treatment did not further modify these parameters. Treatment with CsA and/or DES decreased circulating levels of testosterone, while testosterone content in the testes was not modified. Although CsA did not affect in vitro release of testosterone, it reduced the stimulatory influence of DES pretreatment on testicular responses to hCG in vitro. Plasma and testicular content of progesterone (P) was increased by DES administration but was not affected by CsA. Both CsA and DES administration decreased plasma 17-OH-Progesterone (17-OH-P) levels, but only CsA decreased testicular 17-OH-P contents. Combined exposure to CsA and DES enhanced the stimulatory effect of hCG on the accumulation of 17-OH-P in the media. Media estradiol levels were not affected by treatment with either CsA or DES. The present results indicate that CsA may interfere with the enhancement of the conversion of P to testosterone in DES-treated rats. As CsA did not change plasma PRL or gonadotropin levels, a direct effect of the drug on the testicular function is suspected.

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“…Ob die Störung der Blut-HirnSchranke die Hypothalamus-Hypophysenachse beeinträchtigt, bleibt allerdings noch zu klären. Darüber hinaus wird unter Cyclosporingabe eine verminderte Testosteronbiosynthese in den Leydigzellen des Hodens durch eine Hemmung der 17 α-Hydroxylase und der 17 β-Hydroxysteroiddehydrogenase beobachtet (26,27).…”

Section: Diskussionunclassified

“…Cyclosporin scheint aber auch über Veränderungen des Sexualhormonhaushaltes Einfluss auf den Knochenstoffwechsel zu nehmen. So konnte in tierexperimentellen Studien ein Cyclosporin-bedingter Androgenmangel bei männlichen Ratten nachgewiesen werden (18,26,27).…”

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Einfluss des Immunsuppressiva-induzierten Hypogonadismus auf den Knochenmetabolismus nach Herztransplantation

Stief¹,

Hy²,

Alt³

et al. 2004

Dtsch med Wochenschr

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OriginalienHintergrund und Fragestellung: Nach Herztransplantation (HTx) kommt es gehäuft zu einer Osteoporose. In wie weit das Auftreten eines Cyclosporin-induzierten Hypogonadismus die Posttransplantations-Osteoporose fördert und welche Therapiemaßnahmen geeignet sind, ist bislang unklar. Ziel dieser Studie war es zu untersuchen, wie häufig bei Männern nach HTx ein Hypogonadismus auftritt und inwiefern dieser sich auf die Knochendichte auswirkt. Des weiteren sollte der Effekt einer Testosteronsubstitution auf die Knochendichte hypogonadaler Patienten überprüft werden. Patienten und Methode: Anhand des Hormonstatus wurden 88Herztransplantierte einer normogonadalen bzw. hypogonadalen Gruppe zugeteilt. Bei Einschluss sowie nach 1 (n = 76) und 2 (n = 38) Jahren wurde die Knochendichte der Lendenwirbelsäule mittels Dual Energy X-Ray Absorptiometrie (DEXA) (g/cm 2 , TScore) untersucht. Alle Patienten erhielten als Basismedikation Kalzium und Vitamin D, hypogonadale Patienten wurden zusätzlich mit Testosteron substituiert.Ergebnisse: 21 Patienten (24%) zeigten unabhängig vom Alter einen Hypogonadismus. Die Knochendichte hypogonadaler Patienten (BMD = 0,8070 g/cm 2 , T-Wert = -2,6514) war gegenüber der normogonadaler (BMD = 0,9882 g/cm 2 , T-Wert = -1,0568) zusätzlich signifikant vermindert (p<0,001). Obwohl hypogonadale Patienten mit Testosteron substituiert wurden, zeigte sich bei den im Verlauf nach 1 bzw. 2 Jahren untersuchten Patienten keine signifikant stärkere Zunahme der Knochendichte gegenü-ber normogonadalen Patienten.Folgerung: Bei männlichen Herztransplantierten fand sich gehäuft ein Hypogonadismus, welcher mit einer signifikant verminderten Knochendichte einherging. Unter einer additiven Testosteronsubstitution war keine signifikante Steigerung der Knochendichte zu beobachten.Background and objective: Accelerated bone loss is a well recognized complication after cardiac transplantation (HTx). The role of an immunosuppressive-induced hypogonadism, a wellknown cause of osteoporosis in men and its prevention are less defined after HTx. The aim of this study was first, to evaluate the incidence of hypogonadism after HTx and its influence on bone mineral metabolism and second, to assess the effect of a testosterone replacement therapy in hypogonadal transplants. Patients and methods:Due to hormonal status, 88 male cardiac transplants were randomised to a normogonadal or hypogonadal group. At baseline as well as after 1 and 2 years bone mineral density (BMD g/cm 2 , T-score) was measured at the lumbar spine with DEXA. All patients received a basic therapy of calcium and vitamin D. The hypogonadal patients received additional testosterone.Results: 21 patients (24%) showed an age-independent hypogonadism. Hypogonadal transplants showed a significant lower BMD (p<0,001) (BMD = 0,8070 g/cm 2 , T-value = -2,6514) than normogonadal patients (BMD = 0,9882 g/cm 2 , T-value = -1,0568). Despite testosterone replacement hypogonadal patients showed no significant additional increase in BMD over 1-2 years compared with the n...

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The Mechanism of Cyclosporineʼs Action in the Inhibition of Testosterone Biosynthesis by Rat Leydig Cells in Vitro1,2

Cited by 20 publications

References 0 publications

Inhibition of 3β- and 17β-hydroxysteroid dehydrogenase activities in rat Leydig cells by perfluorooctane acid

Inhibition of 3β- and 17β-hydroxysteroid dehydrogenase activities in rat Leydig cells by perfluorooctane acid

Modulation of the Testicular Steroidogenic Pathway by Cyclosporin A in Adult Rats Pretreated with Diethylstilbestrol

Einfluss des Immunsuppressiva-induzierten Hypogonadismus auf den Knochenmetabolismus nach Herztransplantation

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