Acute response of testicular interstitial tissue in rats to the cytotoxic drug ethane dimethanesulphonate

Kerr, J. B.; Bartlett, John M.S.; Donachie, K.

doi:10.1007/bf00251057

Cited by 46 publications

(16 citation statements)

References 32 publications

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“…Therefore, this process clearly was not affected by the thyroid status of the rat. Similar to previously published reports [17,18,[23][24][25][26][27][28][29][30][31], no Leydig cells were detected in the present study during the first 2 wk following EDS administration, but Leydig cells were seen at Day 21. Evidence has also been presented previously [24,27] for a mesenchymal origin for the newly formed Leydig cells in the EDS-treated rat testis, and their site of differentiation has been described as peritubular and perivascular.…”

Section: Discussionsupporting

confidence: 89%

“…Based on these findings, we suggest that the peritubular mesenchymal cells are the principal, if not the only, precursor cells for the new generation of Leydig cells in the EDS-treated adult rats. Similarly, peritubular mesenchymal cells have been observed as the precursor cells for the adult Leydig cells in prepubertal rat testis [2,19,23,32], except for one report that suggests the mesenchymal cells in the central interstitium as the Leydig cell precursors [33]. It is difficult for us to accept this suggestion, however, which is contradictory to the findings of many others in the field, especially because this statement has not been justified in the said study [33] or in a followup study using appropriate markers to identify these precursor cells [34].…”

Section: Discussionmentioning

confidence: 97%

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Effects of Thyroid Hormone on Leydig Cell Regeneration in the Adult Rat Following Ethane Dimethane Sulphonate Treatment1

Ariyaratne

Mills

Mason

et al. 2000

Biology of Reproduction

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We tested the effects of thyroid hormone on Leydig cell (LC) regeneration in the adult rat testis after ethane dimethyl sulphonate (EDS) treatment. Ninety-day-old, thyroid-intact (n = 96) and thyroidectomized (n = 5) male Sprague-Dawley rats were injected intraperitoneally (single injection) with EDS (75 mg/kg) to destroy LC. Thyroid-intact, EDS-treated rats were equally divided into three groups (n = 32 per group) and treated as follows: control (saline-injected), hypothyroid (provided 0.1% propyl thiouracil in drinking water), and hyperthyroid (received daily subcutaneous injections of tri-iodothyronine, 100 microg/kg). Testing was done at Days 2, 7, 14, and 21 for thyroid-intact rats and at Day 21 for thyroidectomized rats after the EDS treatment. Leydig cells were absent in control and hyperthyroid rats at Days 2, 7, and 14; in hypothyroid rats at all ages; and in thyroidectomized rats at Day 21. The LC number per testis in hyperthyroid rats was twice as those of controls at Day 21. 3beta-Hydroxysteroid dehydrogenase (LC marker) immunocytochemistry results agreed with these findings. Mesenchymal cell number per testis was similar in the three treatment groups of thyroid-intact rats on Days 2 and 7, but it was different on Days 14 and 21. The highest number was in the hypothyroid rats, and the lowest was in the hyperthyroid rats. Serum testosterone levels could be measured in control rats only on Day 21, were undetectable in hypothyroid rats at all stages, and were detected in hyperthyroid rats on Days 14 and 21. These levels in hyperthyroid rats were twofold greater than those of controls on Day 21. Serum androstenedione levels could be measured only in the hyperthyroid rats on Day 21. Testosterone and androstenedione levels in the incubation media showed similar patterns to those in serum, but with larger values. These findings indicate that hypothyroidism inhibits LC regeneration and hyperthyroidism results in accelerated differentiation of more mesenchymal cells into LC following the EDS treatment. The observations of the EDS-treated, thyroidectomized rats confirmed that the findings in hypothyroid rats were, indeed, due to the deficiency of thyroid hormone.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 97%

Effects of Thyroid Hormone on Leydig Cell Regeneration in the Adult Rat Following Ethane Dimethane Sulphonate Treatment1

Ariyaratne

Mills

Mason

et al. 2000

Biology of Reproduction

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“…Taken together, these data with the rabbit are consistent with the effects seen in the rat [7,25], in that T production was impaired after LH binding and before cholesterol side-chain cleavage. Finally, there is considerable research in the rat to indicate that EDS acts directly on the Leydig cell to reduce its capacity to produce T, cause ultrastructural damage, and eventually kill the cell [2,3].…”

Section: Fig 3 A) Electron Micrograph Of Adult Rabbit Leydig Cells mentioning

confidence: 98%

“…In vivo exposure to 75-100 mg/kg ethane-dimethanesulfonate (EDS) selectively kills Leydig cells in adult rat testes [1][2][3][4][5][6]. Degenerative changes are seen histologically within 6 h after dosing.…”

Section: Introductionmentioning

confidence: 98%

Effects of Ethane Dimethanesulfonate (EDS) on Adult and Immature Rabbit Leydig Cells: Comparison with EDS-Treated Rat Leydig Cells1

Laskey¹,

Klinefelter²,

Kelce³

et al. 1994

Biology of Reproduction

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Ethane-dimethanesulfonate (EDS) has been shown to selectively kill Leydig cells and depress testosterone production in adult rats. A recent study has shown that immature rat Leydig cells are less sensitive to EDS exposure. There is evidence that the rabbit metabolizes EDS to methane sulfonic acid more rapidly than does the rat, reducing exposure to the parent compound. In the study reported here, we examined the effects of EDS on the Leydig cells in both adult and immature rabbits and compared the effects found with those previously reported in the rat. In vivo, EDS exposure demonstrated that Leydig cells from adult rabbits were affected, with both serum and interstitial testosterone production depressed. EDS effects in adult rabbits and rats were compared by exposing explants of testicular parenchyma to EDS in vitro and evaluating testosterone production. With this procedure, the rabbit testis was less sensitive to EDS treatment than the rat, with a 50% reduction rate (EC50) achieved with 2026 microM EDS for the rabbit and with 336 microM EDS for the rat. Perfusion of adult and immature rabbit testis with 430 microM EDS demonstrated the insensitivity of the immature testis to EDS exposure: adult testosterone production was reduced 50% in 3.5 h, whereas no diminution was found in the immature rabbit. EDS exposure of interstitial cell preparations further demonstrated the insensitivity of immature rabbit Leydig cells, with an EC50 of 4397 microM compared to an EC50 of 1137 microM EDS in adult preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Although EDS destroys the Leydig cells in the testis of the adult Bartlett & Donachie, 1986;Morris et al 1986) and neonatal rat (Kerr, Risbridger & Knell, 1988;Zaidi, Lendon, Dixon & Morris, 1988), it has been reported that in the adult rat a further chal¬ lenge with EDS is not cytotoxic to the regenerating population of immature Leydig cells (Morris, 1985;Kerr & Knell, 1987). Since Leydig cells of immature rat testes are also reported to be resistant to the cytocidal effect of EDS (Molenaar, de Rooij, Rommerts et al 1985;Morris, 1985;Rommerts, Grootenhuis, Hoogerbrugge & van der Molen, 1985) maturational changes might be involved in the development of sus¬ ceptibility to EDS toxicity.…”

Section: Introductionmentioning

confidence: 95%

Leydig cell recovery following a second challenge with ethane-1,2-dimethanesulphonate is enhanced by short intervals between cytotoxin administration to rats

Edwards

Lendon²,

Morris³

1989

Journal of Endocrinology

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Ethane-1,2-dimethanesulphonate (EDS) destroys Leydig cells in the testis of the adult rat and subsequently a new population of Leydig cells develops. It has been reported that EDS is not cytocidal to the new immature Leydig cell population. In the present study, the effect of increasing the time-interval between injections of EDS on cytotoxicity to Leydig cells was examined. At time-intervals of 4-10 weeks between injections the response was similar to that seen after a single injection of EDS to the adult rat. Four days after the second injection, EDS was found to reduce substantially serum testosterone concentrations and in-vitro binding of 125I-labelled human chorionic gonadotrophin (hCG) to testicular LH receptors which can be correlated with Leydig cell destruction. However, when the interval was only 2 or 3 weeks there was no reduction in serum testosterone, and 125I-labelled hCG binding was not so markedly reduced. During days 1-6 after a second injection of EDS, administered 3 weeks after the first, there were marked reductions in serum testosterone concentrations and in 125I-labelled hCG binding to testis homogenates within 24 h. Recovery from the effects of EDS was rapid, and increased Leydig cell activity was seen from 2 to 6 days after injection. In contrast to the established changes in the adult rat, there was only a 50% reduction in the number of Leydig cells positive for 3 beta-hydroxysteroid dehydrogenase 2 days after the second injection of EDS, and after 6 days the number of cells had increased.(ABSTRACT TRUNCATED AT 250 WORDS)

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Acute response of testicular interstitial tissue in rats to the cytotoxic drug ethane dimethanesulphonate

Cited by 46 publications

References 32 publications

Effects of Thyroid Hormone on Leydig Cell Regeneration in the Adult Rat Following Ethane Dimethane Sulphonate Treatment1

Effects of Thyroid Hormone on Leydig Cell Regeneration in the Adult Rat Following Ethane Dimethane Sulphonate Treatment1

Effects of Ethane Dimethanesulfonate (EDS) on Adult and Immature Rabbit Leydig Cells: Comparison with EDS-Treated Rat Leydig Cells1

Leydig cell recovery following a second challenge with ethane-1,2-dimethanesulphonate is enhanced by short intervals between cytotoxin administration to rats

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