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PubMed1991

Identification and purification of a human Sertoli cell-secreted protein (hSCSP-80) stimulating Leydig cell steroid biosynthesis.

Human Sertoli cells in vitro secrete a factor that stimulates steroid biosynthesis in purified human and rat Leydig cells as well as in the MA-10 mouse tumor Leydig cell line. MA-10 cells were used as a bioassay system to follow the characterization and purification of the active principle in the conditioned medium of human Sertoli cells. The Leydig cell stimulatory factor is a thermo-labile and trypsin-sensitive protein retained onto 10,000 mol wt (MW) cut-off filters. The following scheme was used to purify the active protein: concentration by ammonium sulfate (80%) precipitation, followed by dialysis using molecularporous membrane tubing of MW cut-off 12,000-14,000, heparin-agarose, Concanavalin-A-Sepharose, and immobilized reactive textile dye affinity chromatography. Yellow 86 and green 19 dyes immobilized on agarose matrix were used. This procedure resulted in the rapid (less than 24-h) purification of a 79,000 +/- 6,082 (n = 3; under denaturating conditions) MW protein which stimulated Leydig cell steroid biosynthesis 25-fold at picomolar concentrations. The MW of the biologically active protein was further confirmed to be around 80,000 by gel filtration chromatography. This 80,000 MW human Sertoli cell-secreted protein (hSCSP-80) was shown to be different from human transferrin, human serum albumin, and rat testibumin. hSCSP-80, by modulating Leydig cell steroid biosynthesis, may play a significant role in the regulation of testicular function.

Aged↗
PubMed1993

Evaluation of possible determinants and consequences of Leydig cell heterogeneity in man.

Leydig cells in the human testis are highly heterogeneous, consisting of variably staining light and dark cells. The basis for this difference is unknown. The present study has assessed whether differing numbers or proportions of dark and light Leydig cells are related: (1) to the pronounced inter-individual variation in testosterone production by isolated Leydig cells, and (2) to differences in structural composition of the testis. Testes (paired weight 6.6-59.48 g) were obtained from 27 men aged 72.9 +/- 9.5 years (range 54-89 years) undergoing orchidectomy as primary treatment for prostatic cancer. Leydig cells were isolated by Percoll-purification and cultured for 20 h under basal and hCG-stimulated conditions. The proportion of light and dark Leydig cells isolated by this method was shown to reflect their proportions in situ, based on the morphometric analysis of fixed testicular tissue from the same men. Leydig cells isolated from all testes produced testosterone in vitro and responded to stimulation by hCG, though the amounts of testosterone produced varied widely between subjects. Because of the latter, samples were grouped into 'low' (n = 9), 'medium' (n = 11) and 'high' (n = 7) groups on the basis of their testosterone production. These groups did not differ in their age, testicular size or gross testicular morphology, though men in the 'high' group tended to have more total Leydig cells per testis. However, there was no overall correlation between testosterone production by isolated Leydig cells and the numbers of light or dark Leydig cells or their ratio or the total number of Leydig cells per testis. The relationship between the volume of light and dark Leydig cells and testicular composition was also assessed. The volume of both types of Leydig cells was strongly correlated (p < 0.001) with the volume of germ cells, but otherwise light and dark Leydig cells correlated positively with different structures. Thus, the volume of light Leydig cells correlated (p < 0.001) with the volume of blood vessels and of peritubular tissue whereas the volume of dark Leydig cells correlated (p < 0.01) with that of the tubular lumen. These differences could indicate differences in regulation and/or function of light and dark Leydig cells. However, the present data do not support the idea that light and dark Leydig cells may differ in their steroidogenic capacity.

Aged↗
PubMed2004

[Leydig cell hypoplasia(agenesis)].

Leydig cell hypoplasia(LCH) or agenesis, which has an autosomal recessive inheritance pattern, is a well defined form of male pseudohermaphroditism resulting from inadequate fetal testicular Leydig cell differentiation. These patients exhibit a wide clinical spectrum that ranges from phenotypic females to males with micropenis, and have low levels of serum testosterone and elevated levels of LH. Recently, it has become clear that defective male sex differentiation in patients with LCH is caused by deficient LH receptor signal transduction. The fetal Leydig cells of LCH patients fail to respond to adequate levels of placental hCG, resulting in inappropriate fetal androgen production. At puberty, adult-type Leydig cells do not mature and do not produce sufficient androgen for normal secondary sex differentiation.

Androgens↗
PubMed1988

Inhibitory effect of Sertoli cell-cultured media on LH binding to mouse Leydig cells in culture.

The aim of this study is to examine the influence of Sertoli cells on LH binding to Leydig cells in culture in immature mice. Leydig cells and Sertoli cells were obtained from the testes of immature C57BL/6Ncrj mice and were cultured in serum-free medium for 7 days. The LH binding to Leydig cells and the FSH binding to Sertoli cells were dependent on incubation time, the number of cells, and the amount of labelled hormone added. The dissociation constant for LH binding to Leydig cells was 7.3 x 10(-10) M. Co-culture of Leydig cells with Sertoli cells for 7 days decreased LH binding to Leydig cells. The binding was 34.9% of that to Leydig cells cultured alone. After cultivation of Leydig cells with spent Sertoli cell-cultured medium (SM) for the last 4 days of the 7-day culture period, LH binding to Leydig cells decreased to as low as 17.4% of that of the controls. For the controls, LH binding was measured in Leydig cells cultured in spent Leydig cell-cultured medium (LM). There was no difference between SM- and LM-cultures in the final survival rate or the percentage of cells showing histochemically demonstrated 3 beta-hydroxysteroid dehydrogenase activity. These data suggest that some factor or factors are secreted from the cultured Sertoli cells and inhibit the binding of LH to Leydig cells in culture.

Animals↗
PubMed1991

Identification of an inhibitory factor from a Sertoli clonal cell line (TM4) that modulates adult rat Leydig cell steroidogenesis.

Sertoli cell produces several biological factors that modulate Leydig cell steroidogenic function by either stimulating or inhibiting its testosterone production. We have evaluated the effect of an inhibitory factor in the spent media of a Sertoli clonal cell line (TM4) which inhibits Leydig cell steroidogenesis. The presence of such an inhibitory factor in TM4 media was bioassayed using Percoll purified Leydig cells isolated from adult rats with purity of greater than 95%. TM4 media inhibited both human chorionic gonadotropin (hCG)-stimulated testosterone and cAMP production by purified Leydig cells dose-dependently but had no apparent effect on 8-bromo-cAMP- and forskolin-stimulated testosterone production. Also it did not interfere with the binding of [125I]hCG to Leydig cells. TM4 media inhibited cholera toxin-stimulated testosterone production as well as forskolin- and cholera toxin-stimulated cAMP production. The mechanism of action of this factor in TM4 media appears to be different from transforming growth factor (TGF-beta) which inhibited both 8-bromo-cAMP- and forskolin-stimulated testosterone production and inhibited the binding of [125I]hCG binding to Leydig cells. The inhibitory factor contained in TM4 media has been partially purified by sequential preparative anion exchange and C-18 reversed-phase high-performance liquid chromatography. In summary, the Sertoli TM4 cell line produces at least one potent inhibitory factor which decreases the responsiveness of purified Leydig cells to hCG stimulation with a dramatically different mechanism from other currently known Leydig cell inhibitory factors; this protein may serve as a valuable tool to study testicular paracrine regulation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMedDate not supplied

Leydig cell differentiation induced by stimulation with HCG and HMG in two patients affected with hypogonadotropic hypogonadism.

In order to elucidate the ultrastructural characteristics of the precursor cell of Leydig cells and its subsequent differentiation, testicular biopsies from two patients with hypogonadotropic hypogonadism, obtained prior to and after treatment with HCG and HMG, were studied in comparison with those of prepubertal, pubertal and postpubertal testes. Prior to HCG and HMG stimulation, the testicular interstitium of both patients showed the following spindle-cell-types: Fibroblasts, myofibroblasts and a cell-type similar to the myofibroblast but differing from it by the arrangement of microfilaments and the development of the smooth endoplasmic reticulum as well as lipid droplets. It may be considered the precursor of Leydig cells. In the following stages of differentiation observed in the biopsies after treatment, there is a progressive involution of microfilaments and rough endoplasmic reticulum, a transient period of hyperplasia of the Golgi complex, and the definitive development of cell components involved in steroid biosynthesis, such as the smooth endoplasmic reticulum, polymorphic mitochondria with tubular cristae, lipid droplets and diverse lysosomal bodies. From early stages of differentiation, gap junctions occurred between the cells. Numerous axon profiles were also present among the cells. Only in a small percentage of cells did vesicle-bearing axons closely appose the Leydig cell membrane.

Adult↗
PubMedDate not supplied

Absence of activating mutations in the hot spots of the LH receptor and Gs-alpha genes in Leydig cell tumors.

Leydig-cell tumors are functioning endocrine tumors that produce T autonomously leading to isosexual precocity in boys and virilization in female patients. Molecular abnormalities such as activating mutations of the luteinizing hormone receptor (LHR), a G protein-coupled receptor, and of the Gs-alpha subunit of G protein have recently been described in these tumors. Both mutations cause continuous activation of the cAMP signaling cascade, autonomous production of T and cell proliferation. We searched for activating mutations in exon 11 of the LHR gene and in exons 8 and 9 of the Gs-a gene, which contain all hot spots for those mutations, in 4 Leydig cell tumors obtained from 4 patients (one boy with LH-independent precocious puberty and 3 women with virilization). DNA was extracted from paraffin-embedded neoplastic and non-neoplastic tissues and from peripheral lymphocytes. Hot spot regions of exons 11 of LHR and exons 8 and 9 of Gs-alpha genes were amplified by PCR and the purified PCR products were directly sequenced. No LHR or Gs-alpha gene mutations were found in the 4 tumors studied. Considering the previously reported mutations found in Leydig cell tumors, the absence of activating mutations in the hot spot regions for activating mutations in these tumors indicate molecular heterogeneity among Leydig cell tumors.

Aged↗
PubMed1991

Effect of an acute exposure of rat testes to gamma rays on germ cells and on Sertoli and Leydig cell functions.

Germ cells and Sertoli and Leydig cell functions were studied from 7 to 180 days after an acute exposure of 2-month-old rat testes to 9 Gy of gamma rays. Body weight, testis and epididymal weights were recorded. Sertoli cell parameters (androgen-binding protein, ABP, in caput epididymis and plasma follicle stimulating hormone, FSH) and Leydig cell parameters (plasma luteinizing hormone, LH, testosterone and prostate and seminal vesicle weights) were determined together with the number of germ cells and Sertoli cells. Irradiation did not affect body weight but significantly reduced testicular and epididymal weights from day 7 and day 15 post-irradiation respectively. The cells killed by irradiation were mainly spermatogonia and preleptotene spermatocytes engaged in replicating their DNA at the time of exposure, but all spermatocytes seemed damaged as they gave abnormal descendent cells. By day 34, only elongated spermatids remained in a few tubules and thereafter very little regeneration of the seminiferous epithelium occurred, except for one rat which showed a better regeneration. Levels of ABP decreased by day 15 when the germ cell depletion had reached the pachytene spermatocytes, whereas FSH and LH levels rose when the number of elongated spermatids decreased. Levels of testosterone and the weight of the seminal vesicles did not change; occasionally, the prostate weight was slightly reduced. These results support our hypothesis that pachytene spermatocytes and elongated spermatids are involved in influencing some aspects of Sertoli cell function in the adult rat.

Animals↗
PubMedDate not supplied

Is Leydig cell steroidogenic function affected by the germ cell content of the seminiferous tubules?

The effect of testicular germ cell content on Leydig cell steroidogenic function in vivo in adult rats was examined. Three experimental paradigms were used to effect germ cell changes. First, a vitamin A-depletion/repletion regimen was used to achieve synchrony at different stages of the cycle of the seminiferous epithelium and thus produce testes with widely differing germ cell contents. Second, long term vitamin A depletion was used to effect germ cell, but not Leydig cell, loss. Third, Leydig cells and germ cells first were eliminated from the testes of adult rats by the administration of ethane 1,2-dimethane sulfonate (EDS) along with testosterone- and estradiol-filled Silastic capsules; Leydig cells were then restored to the germ cell-depleted testes by removal of the luteiniging hormone (LH)-suppressing capsules. Serum, interstitial fluid, and seminiferous tubule fluid testosterone concentrations did not differ between rats in which at least 70% of the seminiferous tubules contained germ cells at stages VII-VIII or at stages XII-III of the cycle. The capacity of the testes of these rats to produce testosterone, assessed by their in vitro perfusion with maximally stimulating LH, also showed no differences despite the differences in germ cell content. Elimination of germ cells throughout the testes by long term vitamin A depletion also did not affect the steroidogenic function of the testes. Finally, the steroidogenic function of Leydig cells restored to germ cell-depleted testes was indistinguishable from that of germ cell-containing controls. These results, taken together, provide evidence supporting the contention that the germ cell content of the testis has little or no effect on testicular steroidogenic function.

Animals↗
PubMed1987

Inhibition of testosterone biosynthesis by ethanol: multiple sites and mechanisms in dispersed Leydig cells.

Isolated rat Leydig cells were incubated for 2 h in sealed polycarbonate tubes under O2/CO2 atmosphere with 10 mIU/ml human chorionic gonadotropin. 20 mmol/l ethanol reduced the concentration of testosterone (16%, P less than 0.025); raised the concentrations of pregnenolone (60%, P less than 0.001), androstenedione (86%, P less than 0.001) and dehydroepiandrosterone (81%, P less than 0.001); but did not change concentrations of progesterone and 17 alpha-hydroxyprogesterone in the incubation medium. Ethanol also raised the lactate/pyruvate ratio in the Leydig cell suspension. 4-Methylpyrazole (0.5 mmol/l) abolished the ethanol-induced changes. The present results suggest that ethanol inhibits testosterone synthesis in isolated rat Leydig cells at the pregnenolone-to-testosterone pathway by inhibiting 3 beta-hydroxy-5-ene-steroid dehydrogenase/5-ene-4-ene-isomerase catalyzed reactions and the conversion of androstenedione to testosterone. These inhibitions are caused by consequences of ethanol metabolism. A likely mechanism for the former inhibition is that the increase in the NADH/NAD+ ratio in Leydig cells leads to inhibition of reactions catalyzed by 3 beta-hydroxy-5-ene-steroid dehydrogenase/5-ene-4-ene isomerase, but the inhibition mechanism operating at the androstenedione-to-testosterone step remains to be characterized.

3-Hydroxysteroid Dehydrogenases↗
PubMed2002

Leydig cell tumors of the testis with unusual features: adipose differentiation, calcification with ossification, and spindle-shaped tumor cells.

We report 19 Leydig cell tumors (LCTs) of the testis with adipose differentiation (n = 12) and/or spindle cell growth (n = 8) in patients 28-70 years of age; three tumors with adipose differentiation showed psammomatous calcifications, two of which also had foci of ossification. In eight tumors fat-like cells apparently derived from lipid accumulation within neoplastic Leydig cells and appeared as focal to prominent clusters in a background of vacuolated, neoplastic Leydig cells. The fat-like cells were usually immunoreactive for Leydig cell markers (inhibin-alpha, calretinin, and melan-A) but were typically strongly positive for the adipose tissue marker, S-100 protein, supporting a hybrid cell phenotype. Four tumors had fat of stromal derivation. In two of these there were intermixed mature adipocytes, but in two others only lipoblastic cells were present. These four tumors lacked vacuolated, neoplastic Leydig cells, and the fat cells in the single case studied were negative for inhibin-alpha and melan-A but positive for S-100. Three of the 12 LCTs with adipose differentiation were clinically malignant, and each had several of the established malignant features. Eight tumors with spindle cells occurred in men 34-70 years of age. Two tumors had ill-defined fascicles of spindle cells, and three showed prominent edematous to myxoid areas with spindle-shaped tumor cells. Two additional tumors had a fibroma-like spindled component that blended with islands of more plump, polygonal to spindle-shaped Leydig cells. Finally, one tumor had foci resembling an unclassified sarcoma that merged with conventional LCT; the spindle cell component in this case did not react for Leydig cell markers in contrast to the spindle cells in five of the six other cases in which immunostains were performed. Spindle cell differentiation, by itself, did not appear to have prognostic significance. Of the six patients with available follow-up, two developed metastases, but their tumors had malignant features apart from spindle cells; the remaining four patients were disease free at a mean of 3.6 years. Awareness of these unusual patterns in LCTs may prevent misinterpretation of fat admixed with neoplastic Leydig cells as evidence of extratesticular growth (a criterion for malignant LCT) may help avoid misdiagnosis of a LCT as a testicular "tumor" of the adrenogenital syndrome (which may contain fat) and may prevent misdiagnosis of a LCT with spindle cells as a sarcoma or unclassified sex cord-stromal tumor.

Adipose Tissue↗
PubMed1990

Involution of human fetal Leydig cells. An immunohistochemical, ultrastructural and quantitative study.

The testes of stillborn fetuses (from 13 to 28 weeks of gestational age), fetuses born alive (from 29 weeks of gestational age) who died a few days later, and infants dying 1 to 8 months after birth were processed for light and electron microscopy. Paraffin-embedded material was stained with the avidin-biotin peroxidase complex (ABC) method for immunohistochemical detection of testosterone (T) in order to quantify the age-related changes in the number of T-positive interstitial cells. This number decreased progressively from the 24th week of gestation up to birth and remained unchanged up to the second month of postnatal life. During the third month of age, the number of T-positive cells rose markedly but fell again from the fourth month to the end of the study. The ultrastructural study revealed the following types of interstitial cells at all ages studied: fibroblast-like cells, myofibroblast-like cells, developed fetal Leydig cells, degenerating fetal Leydig cells and infantile Leydig cells with a multilobed nucleus and focal cytoplasmic accumulations of smooth endoplasmic reticulum and lipid droplets. Quantitative ultrastructural studies revealed that the changes in the number of fetal Leydig cells with age were similar to those found in the number of T-positive cells although, for each age studied, absolute values were higher in the ultrastructural study. The number of infantile Leydig cells increased with age.

Aging↗
PubMedDate not supplied

Gonadotropin-mediated regulation of the murine VEGF expression in MA-10 Leydig cells.

Presence of vascular endothelial growth factor (VEGF) is not only limited to cells directly involved in angiogenesis but has also been demonstrated in steroidogenic cells like testicular Leydig cells. Because Leydig cells are subjected to regulation by gonadotropic hormones and produce steroid hormones, we have investigated here the effects of human chorionic gonadotropin (hCG) or steroid hormones on VEGF expression in cultured mouse tumor Leydig cells (MA-10 cells) and have then analyzed the underlying molecular mechanisms. Northern blot analysis and enzyme-linked immunosorbent assays revealed increases in VEGF mRNA and protein levels, respectively, over 3-20 hours in MA-10 cells after stimulation with hCG or 8-Br-cAMP. Although MA-10 cells lack the classical progesterone receptor, progesterone was able to stimulate VEGF expression. Promoter analyses and antibody supershift experiments suggested that the proximal region is able to constitutively bind the transcription factors Sp1 and Sp3. Mutations of 2 potential Sp1 binding sites in the proximal region showed the requirement of these motifs for stimulation of VEGF by hCG and 8-Br-cAMP. The distal cytosine-rich sequence interacts with so far-unidentified faster migrating factors. Following stimulation with hCG or 8-Br-cAMP, the binding of these proteins was increased in the complexes formed in the proximal and distal regions. VEGF expression in Leydig cells is regulated by gonadotropin via a cAMP-dependent mechanism, and the transcription factors Sp1 and Sp3 appear to be involved in the activation of the promoter. Progesterone also appears to play a role in the regulation of VEGF, acting presumably via a nonconventional receptor that remains to be characterized yet.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMedDate not supplied

Tumor necrosis factor and interleukin-1 stimulate testosterone secretion in adult male rat Leydig cells in vitro.

The actions of two cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), on testosterone production by dispersed adult testis cells and purified Leydig cells in culture were studied. In one set of experiments, testis cells from adult (90-day-old) rats were enzymatically dispersed. In another set of experiments, the dispersed testis cells were placed on a Percoll density gradient and were centrifuged to yield purified (greater than 85%) Leydig cells. Both whole testis cells and purified Leydig cells were cultured in the presence of varying doses of TNF or IL-1 with or without maximally stimulating doses of human chorionic gonadotropin (hCG). Both TNF and IL-1 stimulated basal secretion of testosterone in whole testis cells, as well as purified Leydig cells. Additionally, both TNF and IL-1 augmented maximally hCG stimulated testosterone secretion. Both cytokines stimulated testosterone secretion by dispersed testis cells as early as 4 hours, and the effect continued for up to 72 hours. The cytokines slightly, but significantly, stimulated testosterone production in purified Leydig cells after 24 hours, and continued for up to 72 hours. We have concluded from this data that TNF and IL-1 stimulate the testosterone secretion by adult rat Leydig cells. While this effect might be mediated through the action of the cytokines on testicular macrophages, there might also be a direct effect on the Leydig cell since augmentation of secretion occurred in purified Leydig cells, as well as whole testis cells. Therefore, TNF and IL-1 may serve as local regulators of Leydig cell function.

Animals↗
PubMed1985

Light and electron microscopical observations on the Leydig cells of the scrotal and abdominal testes of naturally unilateral cryptorchid West African dwarf goats.

The structure of interstitial cells of Leydig in the scrotal and abdominal testes of adult West African dwarf goats was studied utilising light and electron microscopy. The Leydig cells in both testes were scattered singly, in cords or clusters in the intertubular connective tissue in close proximity to vascular elements. The intertubular connective tissue in the abdominal testes was however much wider because of the hypoplasia of the seminiferous tubules. While the cells of the scrotal testes exhibited non-granular, pale staining cytoplasm, those of the abdominal testes were darkly staining and the majority contained coarse intracytoplasmic osmiophilic granules Interspersed amongst these cells were adipose cells occasionally distributed overall. With the electron microscope, it was found that agranular endoplasmic reticulum, Golgi apparatus and mitochondria were more prominently developed in the scrotal testes. In marked contrast, there were numerous lipid droplets in the cytoplasm of the Leydig cells in the abdominal testes. Furthermore, the cytoplasm of several of these cells showed evidence of degeneration. It is concluded that, contrary to observations in the experimentally induced condition, abdominal retention of testes in natural unilateral cryptorchidism induces alterations in the light microscopical and ultrastructural features of the Leydig cells of West African dwarf goats, changes which possibly can be ascribed to the chronic decline in testicular blood flow and the elevated temperature of the abdominal environment.

Abdomen↗
PubMed1982

[Electron microscopic investigation on the postnatal development of human Leydig cells].

The development of Leydig cells from the 1st to the 14th year was electron microscopically investigated in specimens of testicles. Leydig cells and their precursor were found in the interstitium. The precursors of the Leydig cells were usually spindle-shaped and contained few organelles and filamentous structures. Leydig cells were usually found in groups. The nucleus was round and eccentric. The most striking feature of Leydig cells was the abundance of smooth endoplasmic reticulum. It was tubular and vacuolar in appearance. Mitochondria possessed cristae of the tubular type and contained occasionally intramitochondrial granules. Glycogen granules and lipid droplets were noted in the cytoplasm. No Reinke crystalloids were found throughout this period. Leydig cells arose from mesenchymal cells via their precursors. Phases of regression of Leydig cells were observed twice, in the 2nd and 3rd years, and from the 9th to the 11th year. In these periods the above-mentioned Leydig cells were seldom observed and only degenerating cells were noted. After the 13th year the Leydig cells increased in size and in number.

Adolescent↗
PubMed2001

Differentiation of the adult Leydig cell population in the postnatal testis.

Five main cell types are present in the Leydig cell lineage, namely the mesenchymal precursor cells, progenitor cells, newly formed adult Leydig cells, immature Leydig cells, and mature Leydig cells. Peritubular mesenchymal cells are the precursors to Leydig cells at the onset of Leydig cell differentiation in the prepubertal rat as well as in the adult rat during repopulation of the testis interstitium after ethane dimethane sulfonate (EDS) treatment. Leydig cell differentiation cannot be viewed as a simple process with two distinct phases as previously reported, simply because precursor cell differentiation and Leydig cell mitosis occur concurrently. During development, mesenchymal and Leydig cell numbers increase linearly with an approximate ratio of 1:2, respectively. The onset of precursor cell differentiation into progenitor cells is independent of LH; however, LH is essential for the later stages in the Leydig cell lineage to induce cell proliferation, hypertrophy, and establish the full organelle complement required for the steroidogenic function. Testosterone and estrogen are inhibitory to the onset of precursor cell differentiation, and these hormones produced by the mature Leydig cells may be of importance to inhibit further differentiation of precursor cells to Leydig cells in the adult testis to maintain a constant number of Leydig cells. Once the progenitor cells are formed, androgens are essential for the progenitor cells to differentiate into mature adult Leydig cells. Although early studies have suggested that FSH is required for the differentiation of Leydig cells, more recent studies have shown that FSH is not required in this process. Anti-Müllerian hormone has been suggested as a negative regulator in Leydig cell differentiation, and this concept needs to be further explored to confirm its validity. Insulin-like growth factor I (IGF-I) induces proliferation of immature Leydig cells and is associated with the promotion of the maturation of the immature Leydig cells into mature adult Leydig cells. Transforming growth factor alpha (TGFalpha) is a mitogen for mesenchymal precursor cells. Moreover, both TGFalpha and TGFbeta (to a lesser extent than TGFalpha) stimulate mitosis in Leydig cells in the presence of LH (or hCG). Platelet-derived growth factor-A is an essential factor for the differentiation of adult Leydig cells; however, details of its participation are still not known. Some cytokines secreted by the testicular macrophages are mitogenic to Leydig cells. Moreover, retarded or absence of Leydig cell development has been observed in experimental models with impaired macrophage function. Thyroid hormone is critical to trigger the onset of mesenchymal precursor cell differentiation into Leydig progenitor cells, proliferation of mesenchymal precursors, acceleration of the differentiation of mesenchymal cells into Leydig cell progenitors, and enhance the proliferation of newly formed Leydig cells in the neonatal and EDS-treated adult rat testes.

Animals↗
PubMed1993

Do Sertoli cells influence the microfilament organization of Leydig cells in coculture?

Since it is known that Sertoli cells modulate steroid production by Leydig cells in vitro, an effort was made to see whether the cytoskeleton is involved in this process. Cocultures of Leydig and Sertoli cells were examined in the light microscope equipped with Nomarski optics. To distinguish Leydig cells from Sertoli cells, a histochemical test for delta 5, 3 beta-hydroxysteroid dehydrogenase activity was performed. To visualize microfilaments (MFs), staining with rhodamine labeled phalloidin was used. In coculture, changes of Leydig cell shape towards regular and rounded as well as an increase of androgen production were observed. Concurrently, changes in the microfilament organization were seen. Stress fibers visible in Leydig cells cultured alone, were dispersed or even disappeared when grown in coculture. This effect was strengthened in the presence of FSH in the culture medium, which was not the case in monoculture of Leydig cells. Results are discussed with respect to a possible stimulation of Leydig cell function by Sertoli cells in vitro.

Actin Cytoskeleton↗