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

1989 ◽  
Vol 123 (2) ◽  
pp. 197-203 ◽  
Author(s):  
G. Edwards ◽  
R. Lendon ◽  
I. D. Morris
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Activity ◽  
Serum Testosterone ◽  
Time Interval ◽  
Cell Recovery ◽  
Cytotoxic Effects ◽  
Adult Rat ◽  
Vitro Binding

ABSTRACT 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 3β-hydroxysteroid dehydrogenase 2 days after the second injection of EDS, and after 6 days the number of cells had increased. These experiments show that the immature Leydig cell of the rat is sensitive to the cytotoxic effects of EDS but that the temporal changes in Leydig cell activity after EDS treatment are different in developing and mature Leydig cell populations. The data are consistent with the view that EDS is preferentially cytotoxic towards steroidogenically active Leydig cells, allowing the resident population of precursor cells to continue to respond to the prevailing homeostatic mechanisms. Journal of Endocrinology (1989) 123, 197–203

Effects of melatonin treatment on Leydig cell activity in the testis of the frog Rana esculenta

Zygote ◽  
2004 ◽  
Vol 12 (4) ◽  
pp. 293-299 ◽  
Author(s):  
Michela d'Istria ◽  
Ismene Serino ◽  
Gaia Izzo ◽  
Diana Ferrara ◽  
Gianluca De Rienzo ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Morphological Changes ◽  
Cell Activity ◽  
Rana Esculenta ◽  
Cellular Adhesion ◽  
Morphological Observation ◽  
Melatonin Treatment ◽  
Testosterone Secretion

This study was conducted to verify the effect(s) of melatonin treatment on frog Leydig cells. Morphological observation after melatonin treatment indicates that many frog Leydig cells show degenerative changes (i.e. heterochromatic nuclei, loss of cellular adhesion) while in adjacent germinal tubules several Sertoli cells show heterochromatic nuclei, confirming the presence of a paracrine effect between interstitial and germinal compartments. The effect of melatonin on frog Leydig cell steroidogenesis was investigated in in vitro experiments; after 6 h of incubation melatonin severely inhibits both control and GnRH-induced testosterone secretion. In addition, in order to verify the effect of indolamine on frog Leydig cell activity, we investigated, by in situ hybridization, the presence of frog relaxin (fRLX, a transcript specifically expressed by these cells) in the testes of melatonin-injected animals after 48 h. fRLX signal completely disappeared from the testis of melatonin-injected frogs. The results of the present study indicate that melatonin treatment provokes Leydig cell morphological changes, blocks GnRH-antagonist-induced testosterone secretion and decreases fRLX expression. Taken together these results strongly indicate that melatonin acts on Leydig cells in the testis of the frog Rana esculenta.

Ethan-1,2-dimethanesulphonate reduces testicular oxytocin content and seminiferous tubule movements in the rat

1987 ◽  
Vol 112 (2) ◽  
pp. 311-NP ◽  
Author(s):  
H. D. Nicholson ◽  
R. T. S. Worley ◽  
S. E. F. Guldenaar ◽  
B. T. Pickering
Keyword(s):  
Leydig Cell ◽  
Seminiferous Tubule ◽  
Leydig Cells ◽  
Contractile Activity ◽  
Histological Study ◽  
Interstitial Cells ◽  
Seminiferous Tubules ◽  
Adult Rats ◽  
Adult Rat

ABSTRACT An oxytocin-like peptide is present in the interstitial cells of the testis, and testicular concentrations of oxytocin have been shown to increase seminiferous tubule movements in vitro. We have used the drug ethan-1,2-dimethanesulphonate (EDS), which depletes the Leydig cell population of the adult rat testis, to examine further the relationships between the Leydig cell, testicular oxytocin and tubular movements. Adult rats were injected i.p. with a single dose of EDS (75 mg/kg) or of vehicle (25% dimethyl sulphoxide). Histological study 3 and 10 days after treatment with EDS showed a reduction in the number of interstitial cells, and levels of oxytocin immunoreactivity were undetectable by radioimmunoassay. Immunostaining revealed very few oxytocin-reactive cells. Spontaneous contractile activity of the seminiferous tubules in vitro was also dramatically reduced, but could be restored by the addition of oxytocin to the medium. Four weeks after EDS treatment, the interstitial cells were similar to those in the control animals both in number and in immunostaining; immunoassayable oxytocin was present and tubular movements were normal. The EDS effect, seen at 3 and 10 days, was not altered by daily treatment with testosterone. However, repopulation of the testes with oxytocin-immunoreactive cells was not seen until 6 weeks in the testosterone-treated animals. We suggest that the Leydig cells are the main source of oxytocin immunoreactivity in the testis and that this oxytocin is involved in modulating seminiferous tubule movements and the resultant sperm transport. The results also imply that testosterone does not play a major role in controlling tubular activity in the mature rat. J. Endocr. (1987) 112, 311–316

Leydig cell resistance to the cytotoxic effect of ethylene dimethanesulphonate in the adult rat testis

1985 ◽  
Vol 105 (3) ◽  
pp. 311-NP ◽  
Author(s):  
I. D. Morris
Keyword(s):  
Seminal Vesicle ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Serum Testosterone ◽  
Male Rats ◽  
Cell Physiology ◽  
Testis Weight ◽  
Endocrine Activity ◽  
Adult Rat ◽  
Seminal Vesicle Weight

ABSTRACT Weekly doses of the Leydig cell cytotoxic ethylene dimethanesulphonate (EDS) were administered to adult male rats in an attempt to study the endocrine activity of the testis in the absence of Leydig cells. One week after the first dose serum testosterone and LH concentrations and seminal vesicle weights were close to levels in castrated rats and testicular human chorionic gonadotrophin (hCG) binding was severely depressed. These changes were maintained for a further week but subsequently began to return to, but did not achieve, control levels. After six weekly doses seminal vesicle weight and serum testosterone concentrations were significantly higher than in the castrated rats. Serum LH concentrations were declining towards control values at 4 weeks but had risen again at 6 weeks. Serum FSH concentrations were raised to about 50% of the value in castrated rats throughout the period studied. Testis weight and hCG binding, which initially fell, were partially restored at 6 weeks and spermatogenesis was recovering. The data show that responses of the testis to multiple doses of EDS are similar to those after a single dose. This apparent resistance indicates that the regenerating Leydig cells are functionally different from the mature Leydig cell. The similarities between the maturing Leydig cell seen after EDS destruction and those in the immature rat suggest that EDS will provide a valuable model for the investigation of Leydig cell physiology. J. Endocr. (1985) 105, 311–316

Accelerated recovery of Leydig cells of the immature rat testis after administration of the cytotoxic ethylene dimethanesulphonate

1988 ◽  
Vol 119 (3) ◽  
pp. 475-NP ◽  
Author(s):  
G. Edwards ◽  
R. G. Lendon ◽  
I. D. Morris
Keyword(s):  
Leydig Cells ◽  
Serum Testosterone ◽  
Hydroxysteroid Dehydrogenase ◽  
Cytotoxic Action ◽  
Immature Rat ◽  
Control Value ◽  
Adult Rat ◽  
Cytocidal Effect ◽  
Old Rats

ABSTRACT A single injection of ethane-1,2-dimethanesulphonate (EDS; 100 mg/kg) selectively destroys Leydig cells in the testis of the adult rat; however, unconfirmed reports indicate that Leydig cells in the immature rat are not affected. In this study the effect of EDS was examined 2 days after treatment of rats aged 20, 25 or 35 days. There was a large reduction in the in-vitro binding of 125I-labelled human chorionic gonadotrophin (hCG) to the homogenates of testes from EDS-treated immature rats. EDS reduced the testosterone content of the testes at all ages studied, but 2 days after injection had only significantly lowered the serum testosterone concentration of 25- or 35-day-old animals. Light microscopic examination of the testis of the 22-day-old rat, 2 days after treatment with EDS, indicated that there were still many cells staining for 3β-hydroxysteroid dehydrogenase. The interstitium also contained numerous atypical cells which did not stain for 3β-hydroxysteroid dehydrogenase. Electron microscopy of testes from the 22-day-old EDS-treated rat showed that Leydig cells were still present in the interstitium together with macrophages and fibroblast-like cells. Six days after EDS treatment of 20-day-old rats, but not 35-day-old rats, there was an increase in the binding of 125I-labelled hCG to testis homogenate to 70% of control value. Testicular testosterone content 6 days after treatment of the 20-day-old rat had risen to 50% of the control testis value. These changes documented in the 20-day-old rat after EDS treatment can be explained by either a cytocidal effect with subsequent repopulation of new Leydig cells which has been described in the adult rat or by a reversible cytotoxic action which has not previously been documented. J. Endocr. (1988) 119, 475–482

scholarly journals Monocyte Chemoattractant Protein-1 stimulates the differentiation of rat stem and progenitor Leydig cells during regeneration

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiangcheng Zhan ◽  
Jingwei Zhang ◽  
Saiyang Li ◽  
Xiaolu Zhang ◽  
Linchao Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Serum Testosterone ◽  
Monocyte Chemoattractant Protein 1 ◽  
Rat Testis ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

Abstract Background Monocyte chemoattractant protein-1(MCP-1) is a chemokine secreted by Leydig cells and peritubular myoid cells in the rat testis. Its role in regulating the development of Leydig cells via autocrine and paracrine is still unclear. The objective of the current study was to investigate the effects of MCP-1 on Leydig cell regeneration from stem cells in vivo and on Leydig cell development in vitro. Results Intratesticular injection of MCP-1(10 ng/testis) into Leydig cell-depleted rat testis from post-EDS day 14 to 28 significantly increased serum testosterone and luteinizing hormone levels, up-regulated the expression of Leydig cell proteins, LHCGR, SCARB1, CYP11A1, HSD3B1, CYP17A1, and HSD17B3 without affecting progenitor Leydig cell proliferation, as well as increased ERK1/2 phosphorylation. MCP-1 (100 ng/ml) significantly increased medium testosterone levels and up-regulated LHCGR, CYP11A1, and HSD3B1 expression without affecting EdU incorporation into stem cells after in vitro culture for 7 days. RS102895, a CCR2 inhibitor, reversed MCP-1-mediated increase of testosterone level after culture in combination with MCP-1. Conclusion MCP-1 stimulates the differentiation of stem and progenitor Leydig cells without affecting their proliferation.

Stimulatory and inhibitory factors of Leydig cell steroidogenesis are secreted simultaneously by the rat seminiferous tubules and do not affect Leydig cell inhibin production in vitro

1994 ◽  
Vol 6 (6) ◽  
pp. 693 ◽  
Author(s):  
JR McFarlane ◽  
Kretser DM de ◽  
GP Risbridger
Keyword(s):  
Conditioned Medium ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Seminiferous Tubules ◽  
Low Doses ◽  
Adult Rat ◽  
Testosterone Production ◽  
Significant Reversal ◽  
The Mean

The effect of conditioned medium from rat seminiferous tubules (at Stages VII-VIII and Stages IX-VI) cultured with or without follicle-stimulating hormone (FSH) on the production of testosterone and immunoactive inhibin by Leydig cells was examined. Low doses of conditioned medium from unstimulated tubules at Stages VII-VIII significantly (P < 0.05) increased the mean testosterone production to greater than 31 +/- 11% over that achieved with luteinizing hormone (LH) alone. At the highest dose, the conditioned medium significantly inhibited (P < 0.05) LH-stimulated testosterone production by 13 +/- 7%. Low doses of conditioned medium from unstimulated tubules at Stages IX-VI increased the mean testosterone production to 22 +/- 10%, whereas at higher doses, a significant reversal in the stimulation occurred although not to the same extent as that found with medium from tubules at Stages VII-VIII. Conditioned medium from FSH-stimulated tubules at Stages VII-VIII and Stages IX-VI, significantly increased testosterone production to 39 +/- 7% and 31 +/- 13% respectively. Immunoactive inhibin production by the Leydig cells remained unaffected by exposure to conditioned medium from FSH stimulated and unstimulated tubules at Stages VII-VIII and Stages IX-VI. The data demonstrate that tubule culture medium contains FSH-modulated activities which can specifically stimulate and inhibit testosterone synthesis by adult rat Leydig cells in vitro and therefore explains the contradictory reports in the literature.

Hormone-induced resistance of rat Leydig cells to the cytotoxic effects of ethane-1,2-dimethane sulphonate

1992 ◽  
Vol 134 (1) ◽  
pp. 85-NP ◽  
Author(s):  
K. J. Teerds ◽  
D. G. de Rooij ◽  
C. J. G. Wensing ◽  
F. F. G. Rommerts
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Relative Number ◽  
Human Chorionic Gonadotrophin ◽  
Cytotoxic Action ◽  
Cell Nuclei ◽  
Cytotoxic Effects ◽  
Adult Rat ◽  
The Third ◽  
Complete Destruction

ABSTRACT Several studies have shown that the cytotoxic agent ethane-1,2-dimethane sulphonate (EDS) specifically destroys Leydig cells in the adult rat testis. It has also been reported that when rats are pretreated with human chorionic gonadotrophin (hCG), administration of EDS does not result in the complete destruction of the Leydig cell population. It has been suggested that hCG pretreatment 'protects' Leydig cells against the cytotoxic action of EDS. In the present study the underlying principles for this resistance to the cytotoxic effects of EDS have been investigated. Within 48 h of the start of daily hCG treatment the number of nuclear profiles of Leydig cells (henceforth called relative number of Leydig cells) had increased from 1014 ± 40 to 1368 ± 30 cells per 1000 Sertoli cell nuclei. Previous experiments have indicated that these newly formed Leydig cells probably develop from differentiating Leydig cell precursors. When EDS is administered concomitantly with the third injection of hCG (2 days after the start of hCG treatment), the relative number of Leydig cells surviving EDS treatment was 388 ± 52 per 1000 Sertoli cells. Hence, there is a similarity between the increase in the relative number of Leydig cells after 2 days of hCG treatment and the relative number of EDS-resistant Leydig cells. The Leydig cells that survived EDS administration showed characteristics which also occur in developing Leydig cells in the immature testis. It is concluded that, in rats pretreated with hCG for 2 days before EDS administration, new Leydig cells with some immature characteristics are formed. One of these characteristics is that these cells are insensitive to EDS. Journal of Endocrinology (1992) 134, 85–90

The influence of luteinizing hormone on the Leydig cells of cryptorchid rat testes

1984 ◽  
Vol 107 (1) ◽  
pp. 110-116 ◽  
Author(s):  
L.J. Wilton ◽  
D. M. de Kretser
Keyword(s):  
Cell Size ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Smooth Endoplasmic Reticulum ◽  
Serum Testosterone ◽  
Pituitary Hormones ◽  
Adult Rats ◽  
Serum Hormone ◽  
Local Feedback

Abstract. The influence of circulating LH levels on Leydig cells from cryptorchid adult rats was examined after ablation of the pituitary. After 2 weeks cryptorchidism, serum FSH and LH levels rose 2-fold while serum testosterone (T) remained unchanged. Leydig cells were hypertrophied and showed an increased response to in vitro hCG stimulation. Two weeks after hypophysectomy (hypox), serum hormone levels (LH, FSH and T), Leydig cell size, cytoplasm, organelle content and in vitro T production were all dramatically reduced. However, when hypophysectomy was combined with cryptorchidism (hypox/crypt), there was an increase in Leydig cell size, compared to hypophysectomy alone, in the presence of very low levels of serum FSH, LH and T. Compared to the hypophysectomised state, the mitochondria were larger and the cytoplasm contained more smooth endoplasmic reticulum. The response of the hypox/crypt testes to in vitro hCG stimulation, though significantly less than the cryptorchid testes, was significantly greater than the hypox testes. These results demonstrate that the changes observed in the Leydig cell after cryptorchidism can occur in the absence of peripheral pituitary hormones and are consistent with the hypothesis that a local feedback loop exists within the testis.

scholarly journals Characteristic of Leydig cells from newborn offspring of female rats with experimental type 1 diabetes

2019 ◽  
pp. 105-109
Author(s):  
Г.В. Брюхин ◽  
С.Д. Антонов
Keyword(s):  
Type 1 Diabetes ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Activity Index ◽  
Cell Activity ◽  
Female Rats ◽  
Interstitial Tissue ◽  
Testis Weight ◽  
Experimental Type

Цель исследования - анализ содержания и субпопуляционного состава клеток Лейдига у потомства самок крыс «Вистар» экспериментальным сахарным диабетом 1 типа в период новорождённости. Методика. Исследования выполнены на белых крысах - самках «Вистар» и их потомстве в возрасте 1 сут. У взрослых половозрелых самок моделировали стрептозотоциновый сахарный диабет 1 типа. Изучены морфофункциональные особенности эндокринных клеток семенников у потомства самок крыс с экспериментальным диабетом 1 типа в ранний неонатальный период. Определяли площадь интерстициальной соединительной ткани семенников, число активных и неактивных эндокриноцитов, вычисляли индекс активности клеток Лейдига, расчитывали коэффициент, отражающий отношение числа клеток Лейдига к суммарному содержанию сперматогенных клеток, а также коэффициент, отражающий отношение суммарного количества интерстициальных гландулоцитов к содержанию сустентоцитов. Результаты. Показано, что у подопытных крысят снижена абсолютная масса семенника и его весовой индекс, увеличена площадь стромы, изменено количество клеток Лейдига и их субпопуляционный состав и, как следствие, изменен индекс активности этих клеток. Выявлено существенное снижение у подопытных животных отношения числа клеток Лейдига к содержанию клеток Сертоли, между которыми существуют определенные паракринные взаимоотношения. Заключение. Выявленные изменения могут являться одной из возможных причин нарушения сперматогенного цикла у потомства самок крыс с экспериментальным сахарным диабетом 1 типа. Numerous clinical observations have shown that maternal diabetes adversely affects pregnancy and childbirth as well as the development and condition of the fetus. These women often give birth to children with signs of diabetic fetopathy. However, the effect of type 1 diabetes mellitus on morphology and function of the male offspring reproductive system is still understudied. The aim of the study was evaluating morpho-functional characteristics of Leydig cells in newborn offspring of female rats with experimental type 1 diabetes. Methods. Experiments were performed on Wistar female rats and their one-day offspring. Type 1 diabetes mellitus was modelled in adult, sexually mature females using streptozotocin. Morpho-functional features of testicular endocrine cells were studied in the offspring of female rats with experimental type 1 diabetes in the early neonatal period. The following indexes were determined: area of testicular interstitial tissue; number of active and inactive endocrinocytes; Leydig cell activity index; the ratio of Leydig cells number to the total number of spermatogenic cells; and the ratio of total number of interstitial glandulocytes to the number of sustentocytes. Results. The offspring of experimental rats had a decreased absolute testis weight and testis weight index; an increased area of interstitial tissue; changes in the count of Leydig cells and their subpopulation composition and resultant changes in the Leydig cell activity index. The ratio of Leydig cell number to Sertoli cell number, which are characterized with paracrine interrelations, was decreased. Conclusion. The found changes may underlie disorders of the spermatogenic cycle in the offspring of female rats with experimental type 1 diabetes.

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