Inhibition of testosterone secretion by digitoxin in rat testicular interstitial cells

Wang, Shyi Wu; Lin, Hong-Da; Hwang, Juey Jen; Wang, Paulus S.

doi:10.1002/(sici)1097-4644(19990701)74:1<74::aid-jcb8>3.0.co;2-z

Cited by 10 publications

(4 citation statements)

References 23 publications

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“…Estrogen directly can retard pubertal Leydig cells development [41] and inhibit testosterone production [42&43]. The current results are in agreement with the results of Lin et al [8] and Wang et al [44] who suggested that digoxin inhibits the production of testosterone in rat testicular interstitial cells, at least in part, via attenuation of the activities of adenylyl cyclase and cytochrome P450 scc .…”

Section: Endocrine-disrupting Chemicals May Disrupt Endocrine Homeostsupporting

confidence: 90%

Adverse Effects of Digoxin , as Xenoestrogen , on some Hormonal and Biochemical Patterns of Male Albino Rats

Helal

Badawi

Soliman

et al. 2013

EJHM

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Background: Xenoestrogens are widely used environmental chemicals that have recently been under scrutiny because of their possible role as endocrine disrupters. Among them is digoxin that is commonly used in the treatment of heart failure and atrial dysrhythmias. Digoxin is a cardiac glycoside derived from the foxglove plant, Digitalis lanata and suspected to act as estrogen in living organisms. Aim of the work:The purpose of the current study was to elucidate the sexual hormonal and biochemical patterns of male albino rats under the effect of digoxin treatment. Material and Methods:Forty six male albino rats (100-120g) were divided into three groups (16 rats for each). Half of the groups were treated daily for 15 days and the other half for 30 days. Control group: Animals without any treatment. Digoxin L group: orally received digoxin at low dose equivalent of 0.0045mg/200g.b.wt. Digoxin H group: administered digoxin orally at high dose equivalent of 0.0135mg/200g.b.wt. At the end of the experimental periods, blood was collected and serum was separated for estimation the levels of prolactin (PRL), FSH, LH, total testosterone (total T), aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), urea, creatinine, total proteins, albumin, total lipids, total cholesterol (total-chol), Triglycerides (TG), low density lipoprotein cholesterol (LDL-chol) and high density lipoprotein cholesterol (HDL-chol). Results:Results showed marked elevation in PRL and FSH levels and significant reduction in LH and total T levels in all treated groups compared to the corresponding controls. Serum enzyme activities (ALT, AST and ALP) and levels of urea, creatinine, total lipids, total-chol, TG and LDL-chol were obviously elevated in all the treated groups as compared to control groups. Marked decline was recorded in the values of total proteins, albumin, A/G ratio and HDL-chol in all the treated groups at the end of the two time intervals of treatment compared to controls. Regarding serum globulin level, treatment of rats with the low dose of digoxin for 15 days induced significant reduction in this parameter, while globulin returned back to its normal level after 30 days of treatment. On the other hand, the high dose of digoxin caused significant decline in serum globulin concentrations at the two time intervals of treatment. Most of the recorded changes in hormonal and biochemical parameters exhibited dose and time-dependent manner. Conclusion:The results of the current research confirmed that digoxin disrupts the sexual hormonal pattern and biochemical parameters. So, we recommend replacing of this drug by others without estrogenic activity, particularly if it is indicated at a high dose or for a long period of time.

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Section: Endocrine-disrupting Chemicals May Disrupt Endocrine Homeostsupporting

confidence: 90%

Adverse Effects of Digoxin , as Xenoestrogen , on some Hormonal and Biochemical Patterns of Male Albino Rats

Helal

Badawi

Soliman

et al. 2013

EJHM

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“…3a,5a-THP infusions reinstated midbrain levels to that of pro-oestrous rats and had no effect on plasma levels. production (28). Dihydrotestosterone, a 5a-reduced metabolite of testosterone, can be reversibly converted to 3a-androstanediol by the enzyme 3a-HSOR within astrocytes (29,30).…”

Section: Discussionmentioning

confidence: 99%

Inhibiting Biosynthesis and/or Metabolism of Progestins in the Ventral Tegmental Area Attenuates Lordosis of Rats in Behavioural Oestrus

Petralia¹,

Jahagirdar²,

Frye

2005

J Neuroendocrinology

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In the ventral tegmental area (VTA), lordosis of rats is facilitated by 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP). Central 3alpha,5alpha-THP results from metabolism of peripheral progesterone, from the ovaries and/or adrenals, by sequential enzymatic activity of 5alpha-reductase and 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR). In addition, in glial cells, cholesterol is converted into pregnenolone by the P450 side-chain cleavage enzyme (P450scc), which is then metabolized to progesterone by 3beta-hydroxysteroid dehydrogenase, and subsequently reduced to 3alpha,5alpha-THP. We hypothesize that, in the VTA, formation of 3alpha,5alpha-THP by both metabolism and biosynthesis is necessary for facilitation of lordosis of female rats. In Experiment 1, naturally-receptive rats received bilateral VTA infusions of a P450scc inhibitor, digitoxin (1 microg/side); a 5alpha-reductase inhibitor, finasteride (10 microg/side); digitoxin (1 microg/side)+finasteride (10 microg/side); or vehicle and were tested 3 h later for lordosis. In Experiment 2, the effects of VTA infusions of digitoxin, finasteride, digitoxin+finasteride, or vehicle on lordosis and midbrain and plasma 3alpha,5alpha-THP levels were examined. In Experiment 3, we investigated whether infusions of 3alpha,5alpha-THP to the VTA reinstated lordosis and midbrain 3alpha,5alpha-THP levels following administration of inhibitors. VTA infusions of digitoxin, finasteride, or digitoxin+finasteride, significantly and similarly reduced lordosis and midbrain, but not plasma 3alpha,5alpha-THP levels, compared to vehicle. Following receipt of inhibitor infusions, 3alpha,5alpha-THP to the VTA restored lordosis and midbrain 3alpha,5alpha-THP levels. These data suggest that, in the VTA, both central biosynthesis of progesterone and metabolism of progesterone (from central and/or peripheral sources) to 3alpha,5alpha-THP are important for mediating lordosis of rats.

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“…The concentrations of plasma and TIF testosterone were measured by RIA as described elsewhere (Wang et al, 1999;Chiao et al, 2002). The sensitivity of the testosterone RIA was 2 pg per tube.…”

Section: Testosterone Riamentioning

confidence: 99%

Role of serum- and glucocorticoid-inducible kinase-1 in regulating torsion-induced apoptosis in rats

Cho¹,

Pu²,

Huang³

et al. 2010

International Journal of Andrology

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Serum- and glucocorticoid-inducible kinase-1 (SGK1) is a serine/threonine protein kinase that responds to various stimuli and mediates cell survival. Although it is known that testicular torsion leads to testicular damage and male infertility, the role of SGK1 in torsion remains unclear. This study investigated whether torsion-induced apoptosis is associated with changes in phosphoinositide-dependent protein kinase-1 (PDK1), SGK1 and forkhead transcription factor FOXO3a expression and/or phosphorylation in rats. Sprague-Dawley rats were divided into four groups: sham (control), 1, 2 and 4 h of unilateral torsion. Bilateral testes, testicular interstitial fluid (TIF) and blood samples were collected immediately after torsion. Our results revealed that SGK1 protein and mRNA were abundantly present in testes and were induced by 2 h of torsion, but that phosphorylation of SGK1, PDK1 and FOXO3a decreased simultaneously. After 2 h of torsion, the testosterone secretion capacity of the primary Leydig cells and testicular interstitial cells (TICs) was impaired and apoptotic spermatogonia and TICs were observed; in addition, the mean seminiferous tubular diameter was decreased. Torsion increased plasma corticosterone levels, but decreased plasma luteinizing hormone and testosterone levels. However, the testosterone levels of the TIF in the ipsilateral testes were significantly enhanced after 2 h of torsion, but suppressed in the contralateral testes. This animal study suggests that PDK1, SGK1 and FOXO3a are involved in torsion-induced apoptosis and that medical therapy should be performed as early as 2 h after the occurrence of torsion to prevent further damage.

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Inhibition of testosterone secretion by digitoxin in rat testicular interstitial cells

Cited by 10 publications

References 23 publications

Adverse Effects of Digoxin , as Xenoestrogen , on some Hormonal and Biochemical Patterns of Male Albino Rats

Adverse Effects of Digoxin , as Xenoestrogen , on some Hormonal and Biochemical Patterns of Male Albino Rats

Inhibiting Biosynthesis and/or Metabolism of Progestins in the Ventral Tegmental Area Attenuates Lordosis of Rats in Behavioural Oestrus

Role of serum- and glucocorticoid-inducible kinase-1 in regulating torsion-induced apoptosis in rats

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