scholarly journals Effects of Osteocalcin on Synthesis of Testosterone and INSL3 during Adult Leydig Cell Differentiation

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Gulfidan Coskun ◽  
Leman Sencar ◽  
Abdullah Tuli ◽  
Dilek Saker ◽  
Mustafa Muhlis Alparslan ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Postnatal Development ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Development Process ◽  
Gnrh Antagonist ◽  
Serum Testosterone ◽  
Male Rats ◽  
Significant Difference ◽  
Adult Leydig Cells

Proliferation and differentiation of adult Leydig cells are mainly completed in puberty. In many studies, apart from normal postnatal development process, it is widely indicated that, through administrating EDS, Leydig cell population is eliminated and regenerated. It is believed that osteocalcin released from osteoblasts, which is responsible for modulating bone metabolism, induces testosterone production in Leydig cells, independent of the HPG axis. In addition, INSL3 produced by Leydig cells, such as testosterone, plays a critical role in bone metabolism and is known to reflect the development process and functional capacities of Leydig cells. This study is aimed at investigating OC-mediated testosterone regulation and INSL3 synthesis during differentiation of adult Leydig cells that are independent of LH. For this purpose, male rats were divided into 2 groups: prepubertal normal rats and adult EDS-injected rats. Each group was divided into 4 subgroups in which GnRH antagonist or OC was applied. After adult Leydig cells completed their development, testicular tissue samples obtained from the sacrificed rats were examined by light-electron microscopic, immunohistochemical, and biochemical methods. Slight upregulation in 3βHSD, INSL3, and GPRC6A expressions along with the increase in serum testosterone levels was observed in groups treated with osteocalcin against GnRH antagonist. In addition, biochemical and microscopic findings in osteocalcin treated groups were similar to those in control groups. While there was no significant difference in the number of Leydig cells reported, the presence of a significant upregulation in INSL3 and GPRC6A expressions and the increase in serum testosterone and ucOC levels were observed. After evaluation of findings altogether, it is put forward that, for the first time in this study, although osteocalcin treatment made no significant difference in the number of Leydig cells, it increased the level of testosterone through improving the function of existing adult Leydig cells during normal postnatal development process and post-EDS regeneration. This positive correlation between osteocalcin-testosterone and osteocalcin-INSL3 is concluded to be independent of LH at in vivo conditions.

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

Effects of recombinant human FSH in immature hypophysectomized male rats: evidence for Leydig cell-mediated action on spermatogenesis

1994 ◽  
Vol 141 (3) ◽  
pp. 449-457 ◽  
Author(s):  
T Matikainen ◽  
J Toppari ◽  
K K Vihko ◽  
I Huhtaniemi
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Function ◽  
Serum Testosterone ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Spermatogenic Cells ◽  
Hypophysectomized Rats ◽  
First Time ◽  
Recombinant Human Fsh

Abstract The mode of FSH actions within the testis was studied in immature hypophysectomized male rats by treatment with recombinant human FSH (recFSH, Org 32489). To elucidate the involvement of Leydig cells and androgens in the maintenance of spermatogenesis in FSH-treated hypophysectomized rats further, the recFSH treatment was given both alone and after destruction of Leydig cells with ethane-1,2-dimethane sulphonate (EDS). Three days after hypophysectomy (at 31 days of age) the rats were given one i.p. injection of vehicle or EDS and, 4 days later, they were implanted with osmotic minipumps releasing either 0·9% (w/v) NaCl or 1 IU recFSH/day. Recombinant FSH alone increased testicular weights 2·5-fold in 7 days (P<0·01). The effect of FSH was similar in EDS-pretreated rats (P<0·01). Testicular testosterone increased from 6·5 ± 1·6 to 16·9 ± 5·3 (s.e.m.) pmol/g tissue (P<0·05) and serum testosterone from 0·12 ± 0·02 to 0·22 ± 0·03 nmol/l (P<0·05) when the rats were treated with recFSH. EDS alone did not affect testicular testosterone but, when combined with recFSH, it totally abolished the stimulatory effect of FSH on testosterone. Testicular binding of 125I-labelled iodo human chorionic gonadotrophin (hCG) and 125I-labelled iodo recFSH was increased 2·5- and 2·1-fold respectively with recFSH treatment (P<0·01). EDS, either alone or with FSH, abolished specific testicular hCG binding (P<0·01), but had no effect on that of recFSH. However, FSH increased its own receptors only in animals not treated with EDS. Histological analysis of the testes revealed that the diameters of the seminiferous tubules increased from 115 ± 6·1 to 160 ± 7·2 μm (P<0·05) with recFSH, and a comparable increase was observed when EDS treatment preceded that of recFSH (143 ± 1·5 μm, P<0·05 vs. controls). Quantification of the spermatogenic cells indicated that recFSH supported the progression of spermatogenesis, as shown by increased number of meiotic and haploid spermatogenic cells (P<0·05). In all EDS-treated animals, spermatogenesis was severely disturbed and only a few spermatids were seen. In conclusion: (1) these results further support the suggestion that FSH has indirect stimulatory effects on Leydig cell function, (2) the completion of meiosis and spermiogenesis are supported by FSH, the effect of which is enhanced by the presence of Leydig cells, suggesting its dependence on androgens, and (3) we show for the first time that FSH is able to stimulate its own receptors only in the presence of Leydig cell-derived factors, probably androgens. Journal of Endocrinology (1994) 141, 449–457

Inhibition of testicular and somatic development after treatment of the postnatal rat with the Leydig cell cytotoxic ethylene dimethanesulphonate

1988 ◽  
Vol 119 (3) ◽  
pp. 467-NP ◽  
Author(s):  
I. D. Morris ◽  
R. G. Lendon ◽  
A. Zaidi
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Serum Testosterone ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Testicular Development ◽  
Interstitial Tissue ◽  
Somatic Development ◽  
Serum Lh ◽  
Loss Of Weight

ABSTRACT The Leydig cell cytotoxic ethylene dimethanesulphonate (EDS) was administered s.c. daily (50 mg/kg) to male rats aged 5–16 days. Apart from loss of weight and that the eyelids unfused earlier, no gross toxicity was observed during treatment. On day 17 testis weights, serum testosterone concentrations, testicular serum testosterone content and 125I-labelled human chorionic gonadotrophin (hCG) binding to testicular homogenates were reduced. Serum LH and FSH concentrations were elevated. The testes did not recover from EDS treatment and at 63 and 120 days were minute (<2% of control), and the prostate and seminal vesicles were small although not completely atrophied. In addition, body weights were substantially reduced. Serum and testicular testosterone and 125I-labelled hCG binding to testicular homogenates were reduced but not absent. Serum LH and FSH concentrations were increased. Light microscopy of the adult testes showed that EDS treatment inhibited the development of the seminiferous tubules. Most of the tubules were devoid of germ cells and Sertoli cells were rare. Occasionally tubules also contained spermatogonia and spermatocytes but no signs of spermiogenesis. The testes were composed mainly of closely packed interstitial tissue with no lymphatic space. The interstitial cells resembled Leydig cells and stained for 3β-hydroxysteroid dehydrogenase. Histochemically identified Leydig cells were absent during treatment but reappeared when treatment was withdrawn. Testicular Leydig cell numbers were only 7% of control values in the 63-day-old EDS-treated rat. The effect on the testis of EDS treatment administered at a crucial time of testicular development may be explained by withdrawal of androgen; however, the systemic effects indicate non-specific toxicity so any explanation of these changes must be viewed with caution. J. Endocr. (1988) 119, 467–474

scholarly journals The Leydig Cell MEK/ERK Pathway Is Critical for Maintaining a Functional Population of Adult Leydig Cells and for Fertility

2011 ◽  
Vol 25 (7) ◽  
pp. 1211-1222 ◽  
Author(s):  
Soichi Yamashita ◽  
Ping Tai ◽  
Jean Charron ◽  
CheMyong Ko ◽  
Mario Ascoli
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Erk Pathway ◽  
Adult Leydig Cells

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
Keyword(s):  
Leydig Cell ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Oestrogen Receptor ◽  
Physiological Role ◽  
Plasma Testosterone ◽  
Testis Weight ◽  
Wild Type ◽  
Significant Difference ◽  
Receptor Beta

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.

scholarly journals Role of gonadotrophins in regulating numbers of Leydig and Sertoli cells during fetal and postnatal development in mice

Reproduction ◽  
2001 ◽  
pp. 227-234 ◽  
Author(s):  
PJ Baker ◽  
PJ O'Shaughnessy
Keyword(s):  
Cell Volume ◽  
Postnatal Development ◽  
Leydig Cell ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Normal Values ◽  
Fold Increase ◽  
Adult Mice ◽  
Number Of Cells

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.

scholarly journals The Production of Testosterone and Gene Expression in Neonatal Testes of Rats Exposed to Diisoheptyl Phthalate During Pregnancy is Inhibited

2021 ◽  
Vol 12 ◽  
Author(s):  
Bin Ji ◽  
Zina Wen ◽  
Chaobo Ni ◽  
Qiqi Zhu ◽  
Yiyan Wang ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Corn Oil ◽  
Serum Testosterone ◽  
Male Rats ◽  
Sprague Dawley ◽  
Testosterone Levels ◽  
Protein Levels ◽  
Gestational Exposure ◽  
Phthalate Plasticizer ◽  
Neonatal Testis

Background: Diisoheptyl phthalate (DIHP) is a phthalate plasticizer, which is a branched phthalate. Here, we reported the effects of gestational exposure to DIHP on testis development in male rats.Methods: Pregnant Sprague-Dawley rats were orally fed with vehicle (corn oil, control) or DIHP (10, 100, 500, and 1,000 mg/kg) from gestational day (GD) 12–21. At GD21, serum testosterone levels, the number and distribution of fetal Leydig cells, and testicular mRNA and protein levels, the incidence of multinucleated gonocytes, and focal testicular hypoplasia in the neonatal testis were measured.Results: DIHP increased the fetal Leydig cell cluster size and decreased the fetal Leydig cell size with LOAEL of 10 mg/kg. DIHP did not affect the fetal Leydig cell number. DIHP significantly lowered serum testosterone levels, down-regulated the expression of steroidogenesis-related genes (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3) and testis descent-related gene (Insl3) as well as protein levels of cholesterol side-chain cleavage enzyme (CYP11A1) and insulin-like 3 (INSL3). DIHP dose-dependently increased the percentage of multinucleated gonocytes with the low observed adverse-effect level (LOAEL) of 100 mg/kg. DIHP induced focal testicular hypoplasia.Conclusion: Gestational exposure to DIHP causes testis dysgenesis in rats.

Sexual Behaviour in Male Healthy Rats: A Comparison Between Indian Tribulus terrestris Linn. Extracts with Protodioscin Standardized Bulgarian Extract

2019 ◽  
Vol 9 (1) ◽  
pp. 32-38
Author(s):  
Mohammed Azeemuddin Mukhram ◽  
Mohamed Rafiq ◽  
Neeraj Kumar ◽  
Atul Namdeorao Jadhav ◽  
Suryakanth Dattatray Anturlikar ◽  
...  
Keyword(s):  
Serum Testosterone ◽  
Male Rats ◽  
Tribulus Terrestris ◽  
Mean Values ◽  
Treatment Groups ◽  
Group I ◽  
Significant Difference ◽  
Respective Treatment ◽  
Sex Stimulant ◽  
Ranking Analysis

Background: Tribulus terrestris Linn. (TT) is reported for its ability to improve male sexual performance, and protodioscin is responsible for the activity. This study was designed to correlate and compare various extracts of Indian TT with Bulgarian TT, and also the effect of protodioscin content on the activity. Methods: Bulgarian TT extract (BT) and prepared solvent extracts [aqueous (WIT), supercritical fluid (SIT) and methanol (MIT)] of Indian TT were standardized and compared using UV spectrophotometric method. Forty male rats were randomized into 5 groups of 8 each. Group I served as untreated control and group II to V were treated with 100 mg/Kg b.wt. of MIT, WIT, BT and SIT, respectively. The groups received the respective treatment for fourteen days. Sexual behavior of the rats was observed on Day-1&14. Serum testosterone was estimated after the last observation. Results: It was found that there was a statistically significant difference between the treatment groups. However, based on the mean values/ranking analysis of all the parameters, the order of potency was WIT > SIT &#8805; BT > MIT. Conclusion: These findings indicate that the aqueous extract of Indian TT which contains lesser protodioscin showed comparatively better sex stimulant activity in comparison to the other tested extracts.

scholarly journals Comparison of cell types in the rat Leydig cell lineage after ethane dimethanesulfonate treatment

Reproduction ◽  
2013 ◽  
Vol 145 (4) ◽  
pp. 371-380 ◽  
Author(s):  
Jingjing Guo ◽  
Hongyu Zhou ◽  
Zhijian Su ◽  
Bingbing Chen ◽  
Guimin Wang ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Pubertal Development ◽  
Cell Lineage ◽  
Hydroxysteroid Dehydrogenase ◽  
Mrna Levels ◽  
Steroidogenic Enzymes ◽  
Isolated Cells ◽  
Adult Leydig Cells

The objective of this study was to purify cells in the Leydig cell lineage following regeneration after ethane dimethanesulfonate (EDS) treatment and compare their steroidogenic capacity. Regenerated progenitor (RPLCs), immature (RILCs), and adult Leydig cells (RALCs) were isolated from testes 21, 28 and 56 days after EDS treatment respectively. Production rates for androgens including androsterone and 5α-androstane-17β, 3α-diol (DIOL), testosterone and androstenedione were measured in RPLCs, RILCs and RALCs in media after 3-h in vitro culture with 100 ng/ml LH. Steady-state mRNA levels of steroidogenic enzymes and their activities were measured in freshly isolated cells. Compared to adult Leydig cells (ALCs) isolated from normal 90-day-old rat testes, which primarily produce testosterone (69.73%), RPLCs and RILCs primarily produced androsterone (70.21%) and DIOL (69.79%) respectively. Leydig cells isolated from testes 56 days post-EDS showed equivalent capacity of steroidogenesis to ALCs and primarily produced testosterone (72.90%). RPLCs had cholesterol side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1 and 17α-hydroxylase but had almost no detectable 17β-hydroxysteroid dehydrogenase 3 and 11β-hydroxysteroid dehydrogenase 1 activities, while RILCs had increased 17β-hydroxysteroid dehydrogenase 3 and 11β-hydroxysteroid dehydrogenase 1 activities. Because RPLCs and RILCs had higher 5α-reductase 1 and 3α-hydroxysteroid dehydrogenase activities they produced mainly 5α-reduced androgens. Real-time PCR confirmed the similar trends for the expressions of these steroidogenic enzymes. In conclusion, the purified RPLCs, RILCs and RALCs are similar to those of their counterparts during rat pubertal development.

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