248. Oestrogen receptor beta is involved in the regulation of Leydig cell number in the mouse

2005 ◽  
Vol 17 (9) ◽  
pp. 99
Author(s):  
M. Gould ◽  
H. D. Nicholson

Recent evidence suggests that oestrogen plays a physiological role in the testis. Both oestrogen receptor alpha and oestrogen receptor beta (ERb) are present in the testis and administration of oestrogen has been shown to inhibit the development of Sertoli, Leydig and germ cells. This study investigates the effect of ERb on the testis using ERb knockout mice (bERKO). Adult male bERKO mice (n=8) and their wild-type littermates (n=7) were killed at 11 weeks postpartum. One testis from each animal was fixed in Bouin’s fluid and embedded. Each testis was fractionated and thick sections cut and stained with PAS. The optical disector method was used to count the number of Leydig cells, Sertoli cells, spermatogonia, spermatocytes and spermatids in each testis. Trunk blood was collected and plasma testosterone concentrations measured by radioimmunoassay. No significant differences in body or testis weight were seen between the bERKO or wild-type mice. Similar numbers of Sertoli cells, spermatogonia, spermatocytes and spermatids were also observed between the two groups. The number of Leydig cells was significantly increased in bERKO mice compared with their wild-type littermates (P < 0.05). Despite the increased number of Leydig cells in the bERKO mice there was no significant difference in plasma testosterone concentrations in this group compared to the wild-type mice. Oestrogen has been reported to inhibit proliferation of adult-type Leydig cells and to inhibit steroidogenesis. This study suggests that the regulation of Leydig cell proliferation may be mediated by ERb. The presence of normal circulating testosterone concentrations in bERKO mice suggests that the effects of oestrogen on steroidogenesis are not brought about by ERbeta.

Reproduction ◽  
2001 ◽  
pp. 419-429 ◽  
Author(s):  
C McKinnell ◽  
PT Saunders ◽  
HM Fraser ◽  
CJ Kelnar ◽  
C Kivlin ◽  
...  

The aims of this study were: (i) to investigate the cellular immunoexpression of androgen receptor and oestrogen receptor beta in the testes of the common marmoset (Callithrix jacchus) during neonatal life compared with their expression at later ages; (ii) to establish whether neonatal marmoset Sertoli cells are targets for androgens or oestrogens or both; and (iii) to investigate the relationship between neonatal plasma testosterone concentrations and androgen receptor immunoexpression by abolishing the neonatal testosterone surge with a potent GnRH antagonist. Androgen receptor and oestrogen receptor beta immunoexpression were evaluated in neonatal animals aged 1-4 days, 4 weeks and 6 weeks, and compared with immunoexpression in animals aged 18-22 weeks (early infancy), 35 weeks (late infancy), 58-62 weeks (late pubertal) and > 100 weeks (adult). Immunoexpression of androgen receptor in the reproductive tract was also evaluated at each age. Sertoli cell immunoexpression of androgen receptor was weak or absent in neonatal animals, but increased substantially in infant animals, reaching adult levels by the end of infancy. In contrast, immunoexpression of androgen receptor during the neonatal period was strong in testicular interstitial cells and very strong in epithelial cell nuclei throughout the reproductive tract, and did not change greatly with age in these cells or tissues. Similarly, immunoexpression of oestrogen receptor beta was prominent in many Sertoli cells and in the germ cells of neonatal animals, and was relatively constant throughout life. Weak immunoexpression of androgen receptor in neonatal Sertoli cells was associated with high plasma testosterone concentrations (2.7-5.5 ng ml(-1)), whereas strong Sertoli cell immunoexpression was associated with baseline (approximately 0.12 ng ml(-1)) testosterone concentrations in infant animals and with > 10 ng ml(-1) in late pubertal and adult animals. Immunoexpression of androgen receptor and oestrogen receptor beta was also evaluated in co-twin males aged 4 and 35 weeks, after treatment from birth to 4 weeks or from week 25 to week 35, respectively, with either vehicle or with GnRH antagonist at a dose known to suppress the neonatal testosterone surge completely. Only GnRH antagonist treatment during weeks 25-35 reduced androgen receptor immunoexpression, whereas immunoexpression of oestrogen receptor beta was unaffected by treatment during either period. On the basis of these findings it is suggested that: (i) neonatal marmoset Sertoli cells may be targets primarily for oestrogens rather than androgens; (ii) androgen receptor expression in the testes of neonatal and infant marmosets is not regulated in a straightforward way by testosterone; and (iii) high neonatal concentrations of plasma testosterone are not absolutely necessary for expression of androgen receptor in marmoset testes at this time.


Author(s):  
Г.В. Брюхин ◽  
С.Д. Антонов

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.


1987 ◽  
Vol 114 (3) ◽  
pp. 459-467 ◽  
Author(s):  
V. Papadopoulos ◽  
P. Kamtchouing ◽  
M. A. Drosdowsky ◽  
M. T. Hochereau de Reviers ◽  
S. Carreau

ABSTRACT Production of testosterone and oestradiol-17β by Leydig cells from adult rats was stimulated by LH or dibutyryl cyclic AMP (10 and 2·5-fold respectively). The addition of spent medium from normal, hemicastrated or γ-irradiated rat seminiferous tubule cultures, as well as from Sertoli cell cultures, to purified Leydig cells further enhanced both basal (44 and 53% for testosterone and oestradiol-17β respectively) and LH-stimulated (56 and 18%) steroid output. Simultaneously, a decrease (20–30%) in intracellular cyclic AMP levels was observed. This stimulating factor (or factors) secreted by the Sertoli cells is different from LHRH, is of proteinic nature and has a molecular weight ranging between 10 000 and 50 000; its synthesis is not controlled by FSH nor by testosterone. This factor(s) involved in rat Leydig cell steroidogenesis, at a step beyond the adenylate cyclase, does not require protein synthesis for testosterone formation whereas it does for oestradiol-17β production. It should be noted that a germ cell–Sertoli cell interaction modulates the synthesis of this factor(s). J. Endocr. (1987) 114, 459–467


1998 ◽  
Vol 156 (3) ◽  
pp. R13-R17 ◽  
Author(s):  
PT Saunders ◽  
JS Fisher ◽  
RM Sharpe ◽  
MR Millar

The identification of a second oestrogen receptor (beta) has prompted a re-evaluation of the potential sites of action of oestrogens. The aim of the present study was to characterize immunoexpression of ER beta expression in the testis to complement earlier data which had demonstrated that expression of ER alpha is confined to testicular interstitial Leydig cells. In all testes studied, including those from both fetal (day 20.5 p.c.) and adult rats, ER beta was found to be expressed in multiple cell types. Sertoli cell nuclei were immunopositive at all ages. In adult testes expression in Sertoli cells was not stage dependent and was unaffected by ablation of Leydig cells. In fetal testes ER beta was also expressed in peritubular cells, fetal Leydig cells and gonocytes. In the pubertal and adult testis ER beta was detected in the nuclei of spermatogonia and most pachytene spermatocytes. Weak immunopositive staining was present in the cytoplasm of spermatocytes undergoing the second meiotic division. In conclusion the widespread expression of ER beta in the testis is consistent with a role for oestrogens in modulating spermatogenesis, and hence fertility, in the male.


Reproduction ◽  
2001 ◽  
pp. 227-234 ◽  
Author(s):  
PJ Baker ◽  
PJ O'Shaughnessy

The role of the gonadotrophins in regulating numbers of Leydig and Sertoli cells during fetal and postnatal development was examined using normal mice and hypogonadal (hpg) mice, which lack circulating gonadotrophins. The disector method was used to determine the number of cells from day 16 of gestation until adulthood. The numbers of Leydig cells did not change significantly between day 16 of gestation and day 5 after parturition in normal mice and were not significantly different from numbers in hpg mice at any age up to day 5 after parturition. There was a 16-fold increase in the number of Leydig cells in normal mice between day 5 and day 20 after parturition, followed by a further doubling of number of cells between day 20 and adulthood. The number of Leydig cells in hpg testes did not change between day 5 and day 20 after parturition but doubled between day 20 and adulthood so that the number of cells was about 10% of normal values from day 20 onwards. Leydig cell volume was constant in normal animals from birth up to day 20 and then showed a 2.5-fold increase in adult animals. Leydig cell volume was normal in hpg testes at birth but decreased thereafter and was about 20% of normal volume in adult mice. The number of Sertoli cells increased continuously from day 16 of gestation to day 20 after gestation in normal mice and then remained static until adulthood. The number of Sertoli cells in hpg testes was normal throughout fetal life but was reduced by about 30% on day 1 (day of parturition). Thereafter, Sertoli cells proliferated at a slower rate but over a longer period in the hpg testis so that on day 20 after parturition the number of Sertoli cells was about 50% of normal values, whereas in adult mice the number was 65% of normal. The number of gonocytes did not change between day 16 of gestation and day 1 and did not differ between normal and hpg testes. The number of gonocytes increased nine-fold in normal testes but only three-fold in hpg testes between day 1 and day 5 after parturition. Gonocytes differentiated into spermatogonia in both normal and hpg testes between day 5 and day 20 after parturition. These results show: (i) that fetal development of both Sertoli and Leydig cells is independent of gonadotrophins; (ii) that normal differentiation and proliferation of the adult Leydig cell population (starting about day 10 after parturition) is dependent on the presence of gonadotrophins; and (iii) that the number of Sertoli cells after birth is regulated by gonadotrophins, although proliferation will continue, at a lower rate and for longer, in the absence of gonadotrophins.


2019 ◽  
Vol 26 (2) ◽  
Author(s):  
Aril Rizaldi ◽  
Doddy M Soebadi ◽  
Soetojo Soetojo

Objective: To analyze the difference in the number of spermatogonia, leydig cells and sertoli cells in young age of  white mice Wistar strain after inhalation of chronic nicotine exposure. Material & Method: Laboratory experimental study with post test only control group design, measurement of spermatogonium, leydig cell, sertoli cell in 5 groups of young male Wistar strain, negative control group and treatment group given nicotine exposure 0.5 mg, 1 mg, 2 mg, and 4 mg/kg body weight/day for 30 days. Results: A significant reduction in spermatogonium was found in the group given nicotine 0.5 mg/kgBW/day (p=0.048), 1 mg/kgBW/day (p=0.002), 2 mg/kgBW/day (p=0.002) and 4 mg/kgBW/day (p=0.000) when compared to the control group. Significant decreases were also seen in the group receiving 4 mg of nicotine exposure compared with 0.5 mg (p=0.018). Significant decrease in sertoli cell count was seen only in the nicotine group of 4 mg/kgBW/day compared with the control group (p=0.047). A significant decrease in leydig cell count was found in the nicotine 2 mg/kgBW/day (p=0.037) and nicotine group 4 mg/kgBW/day (p=0.023) when compared with the control group. Significant decreases were also found in the 4 mg/kgBW/day group compared to the 0.5 mg/kgBW/day group (p=0.004). In this study there were also a decrease in the number of spermatogonia, sertoli cells, and leydig cells in the increased dose of nicotine given although not statistically significant. Conclusion: Chronic exposure of nicotine per inhalation may decrease the number of spermatogonia, sertoli cells, and leydig cells. The higher the dose of nicotine given the greater the decrease in the number of spermatogonium cells, sertoli cells, and leydig cells that occur. This proves that nicotine is one of the causes of infertility in men.


2009 ◽  
Vol 52 (6) ◽  
pp. 1461-1472 ◽  
Author(s):  
Jaqueline Carlos ◽  
Sérgio Luis Pinto da Matta

The aim of this work was to study the testicular morphometry of captivity-bred adult bullfrogs. Fifteen young adult male were studied, in the rainy season and a lengthy photoperiod. The GSI was established at 0.15%. The nuclear diameter of germinative and Leydig cells, the nucleolus diameter of Sertoli cells and the area of cysts and tubules were determined and the mean number of ISPC, IISPC and SPT per cyst and the mean number of cysts per tubule was estimated. The nucleoplasmatic proportion of the nucleus of the Leydig cell was 76.22%, indicating less cytoplasmic activity. Eight generations of spermatogonia were found. The spermatogenesis efficiency in meiosis and in mitosis was 63 and 49%, respectively. The spermatogenesis of bullfrog fited in the pattern of other captivity Anurans, with differences as the morphology of Sertoli and Leydig cells nuclei.


2008 ◽  
Vol 20 (9) ◽  
pp. 80
Author(s):  
R. Anand-Ivell ◽  
J. Manson ◽  
G. Wittert ◽  
J. Wohlgemuth ◽  
B. Hafen ◽  
...  

Insulin like factor 3 (INSL3) and testosterone are the two major secretory products of the testis, both produced by the interstitial Leydig cells. The Leydig cells of the testis have two distinct generations, one developing before birth (fetal Leydig cells, FLC) and an adult type (adult Leydig cells, ALC) that become differentiated and functional at puberty. Although these two types of Leydig cells represent distinct populations, rodent studies show that both types produce testosterone and INSL3. Both are presumed to have evolved from a common stem cell pool. We measured INSL3 levels in human amniotic fluids collected at various times of gestation and show for the first time that the human male fetus indeed generates INSL3 at a time appropriate for the first transabdominal phase of testicular descent, which appears to be the primary physiological role for the fetal hormone. INSL3 appears to be independent of androgen production. The adult type Leydig cells (in adult men) secrete INSL3 that can be measured in the peripheral circulation at levels ranging from 0.5 to 2.5 ng/mL. We studied a large randomly recruited cohort of 1183 men from South Australia, comparing serum INSL3 concentrations with age, and a variety of endocrine, cognitive and morphological parameters. INSL3 concentration was observed to decline significantly with age. This however, had no correlation with testosterone or components of the HPG axis. INSL3 is an independent measure of Leydig cell function (quality and number), which appears to be independent of acute control via the HPG axis. Its decline with age reflects a decline in the properties of the Leydig cell population only, and emphasises a gonadal component in the age-related decrease in androgen production. Research supported by ARC Discovery grant DP0773315.


Development ◽  
1986 ◽  
Vol 95 (1) ◽  
pp. 261-277
Author(s):  
C. J. A. H. V. van Vorstenbosch ◽  
C. M. J. E. van Rossum-Kok ◽  
B. Colenbrander ◽  
C. J. G. Wensing

Testes of foetal pigs between 26 to 35 days post coitum (p.c.) were investigated histochemically and ultrastructurally. Diaphorase and Δ5-3β-hydroxysteroid dehydrogenase activities were studied using, respectively, NADH and pregnenolone and dihydroxy androsterone as substrates. Ultrastructurally, attention was focused on the development of mesenchymal cells and on the sustentacular cells in the primitive sex cords in an attempt to detect the origin of Ley dig cells. Histochemically there is a concentration of activity toward the interstitium with increasing age. Also the reactions increase in intensity. Ultrastructurally no evidence for Leydig cell development from Sertoli cells could be observed. Mesenchymal cells between the sex cords show a development toward Leydig cells. This is absent in mesenchymal cells in the future tunica albuginea. Before 30 days p.c. no ‘true’ Leydig cells can be observed morphologically. The role of the rough endoplasmic reticulum/mitochondrial complex, which is present in many mesenchymal and sustentacular cells, is discussed.


Reproduction ◽  
2010 ◽  
Vol 139 (1) ◽  
pp. 177-184 ◽  
Author(s):  
P J O'Shaughnessy ◽  
A Monteiro ◽  
G Verhoeven ◽  
K De Gendt ◽  
M H Abel

FSH and androgen act to stimulate and maintain spermatogenesis. FSH acts directly on the Sertoli cells to stimulate germ cell number and acts indirectly to increase androgen production by the Leydig cells. In order to differentiate between the direct effects of FSH on spermatogenesis and those mediated indirectly through androgen action, we have crossed hypogonadal (hpg) mice, which lack gonadotrophins, with mice lacking androgen receptors (AR) either ubiquitously (ARKO) or specifically on the Sertoli cells (SCARKO). These hpg.ARKO and hpg.SCARKO mice were treated with recombinant FSH for 7 days and testicular morphology and cell numbers were assessed. In untreated hpg and hpg.SCARKO mice, germ cell development was limited and did not progress beyond the pachytene stage. In hpg.ARKO mice, testes were smaller with fewer Sertoli cells and germ cells compared to hpg mice. Treatment with FSH had no effect on Sertoli cell number but significantly increased germ cell numbers in all groups. In hpg mice, FSH increased the numbers of spermatogonia and spermatocytes, and induced round spermatid formation. In hpg.SCARKO and hpg.ARKO mice, in contrast, only spermatogonial and spermatocyte numbers were increased with no formation of spermatids. Leydig cell numbers were increased by FSH in hpg and hpg.SCARKO mice but not in hpg.ARKO mice. Results show that in rodents 1) FSH acts to stimulate spermatogenesis through an increase in spermatogonial number and subsequent entry of these cells into meiosis, 2) FSH has no direct effect on the completion of meiosis and 3) FSH effects on Leydig cell number are mediated through interstitial ARs.


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