The ultrastructure of testicular tumours in the dog: II. Leydig cells and Leydig cell tumors.
Explore the source record for details and available documents.
Animals↗
SEARCH · PubMed Health
Results for “Leydig Cells”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The effect of lutropin on specific protein synthesis in tumour Leydig cells and in Leydig cells from immature rats.
The amount of (35)S incorporated into the various proteins after separation by electrophoresis on sodium dodecyl sulphate/polyacrylamide gels was used as an estimate of their synthesis in the Leydig cells. Increased synthesis of proteins with apparent mol.wts. 27000 and 29000 was observed 3h after addition of lutropin to tumour Leydig cells. Incubation of Leydig cells from immature rats with lutropin (100ng/ml) for 2h or longer resulted in increased synthesis of proteins with apparent mol.wts. 11000, 21000, 27000 and 29000. At higher concentrations (>/=100ng/ml) of lutropin there was a decrease in the synthesis of a protein with apparent mol.wt. 13000. The amount of lutropin required for the stimulation of protein synthesis in both types of Leydig cells was similar to that needed for stimulation of steroidogenesis. Lutropin-stimulated specific protein synthesis was not due to increased concentrations of testosterone, however, because (1) addition of testosterone to the cells had no effect on the synthesis of the proteins, and (2) inhibition of steroidogenesis with elipten phosphate (an inhibitor of the cholesterol side-chain-cleavage enzyme complex) did not abolish the effect of lutropin. The stimulation of specific protein synthesis was also not due to contaminating follitropin in the lutropin preparation. Addition of actinomycin D to the cells at the start of the incubation prevented the effect of lutropin on specific protein synthesis, indicating that mRNA synthesis may be needed for this effect of lutropin. Incubation of the cells with cycloheximide for 30min after labelling of the proteins did not result in a detectable decrease in the amounts of the lutropin-induced proteins, indicating that their half-life is longer than 30min.
Age Factors↗
Can radiation induce interstitial-cell (Leydig-cell) tumours of the testis?
Explore the source record for details and available documents.
Animals↗
Response of adult rat Sertoli cells and Leydig cells to depletion of luteinizing hormone and testosterone.
Explore the source record for details and available documents.
Animals↗
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↗
Leydig-cell agenesis: a cause of male pseudohermaphroditism.
We studied a 35-year-old patient with female external genitalia, primary amenorrhea and XY karytotype. Plasma testosterone was 10 ng per deciliter, which did not change after administration of human chorionic gonadotropin, increased to 22 ng per deciliter after ACTH, and decreased to 0.9 ng per deciliter after dexamethasone. Plasma delta 4-androstenedione, dehydroepiandrosterone and 17-hydroxyprogesterone were in the normal range. Plasma luteinizing hormone was high, but follicle-stimulating hormone normal (7.5 mlU per milliliter). There were two testes with epididymis and vas deferens, but no Mullerian structures. Microscopical examination showed hyalinization of tubules, which were lined by normal Sertoli cells and occasional immature germ cells. No Leydig cells were seen. After castration follicle-stimulating hormone increased to 43 mlU per milliliter. We conclude that this case of male pseudohermaphroditism was probably due to a Leydig-cell agenesis, that the epididymis and vas deferens can be developed in such a condition and the follicle-stimulating hormone secretion is regulated, at least in part, by a non-androgen substance secreted by Sertoli cells.
Adrenal Glands↗
Quantitation of Leydig cells in testicular biopsies of oligospermic men with varicocele.
Leydig cell density was evaluated quantitatively in bilateral testicular biopsies from 16 oligospermic men with varicocele. The method utilized for this quantitation is based on the determination of the total number of Leydig cells, Leydig cell clusters, and seminiferous tubules in the entire histologic section of each biopsy, and the calculation of the following indices: mean Leydig cells per seminiferous tubule, mean Leydig cell clusters per seminiferous tubule, and mean Leydig cells per cluster. A significant correlation between Leydig cells per tubule and Leydig cell clusters per tubule was demonstrated, suggesting that determination of Leydig cell clusters per seminiferous tubule in testicular biopsies is an objective and clinically applicable method for quantitative evaluation of Leydig cell density. An association of varicocele with Leydig cell hyperplasia was not noted for the 16 patients studied. In addition, no significant differences in Leydig cell density between right and left testes were found, and no correlation between Leydig cell density and site or degree of varicocele, or age of the patients could be demonstrated. To our knowledge this is the first report of quantitative analysis of Leydig cell density in men with varicocele.
Biopsy↗
A study of the capacity for regeneration of rat and human Leydig cells.
The capacity of Leydig cells for regeneration was investigated in 12 patients with prostatic carcinoma, who underwent subcapsular orchidectomy, and in rats after testicular necrosis produced by cadmium chloride. In rats, reappearance of Leydig cells originating from the tunica albuginea could be demonstrated by histology. Testosterone concentrations increased parallel to regeneration of Leydig cells, while LH concentrations declined. In contrast to these findings, no rise of testosterone concentrations could be observed in patients up to 8 months after subcapsular orchidectomy. Human Leydig cells seem to have no capacity for regeneration, or endocrine function, despite the fact that some of these cells, which are present morphologically in the tunica albuginea or spermatic cord, remained.
Animals↗
Leydig cell tumors of the testis.
Leydig cell tumors represent approximately one to three percent of all testicular tumors. Whereas in experimental animals predisposing conditions include administration of chemical carcinogens, hormones and heavy metals, environmental or endogenous factors in man are presently unrecognized. Leydig cell tumors do not show preferential lateralization or tendency for bilaterality. The symptoms are related to the local effects or to hormones released into the systemic circulation. Laboratory findings are variable, depending on endocrinological activity. Typical tumors rarely exceed five cm in diameter, are brown on cross section and are composed of polyhedral cells with acidophilic, granular cytoplasm. Ultrastructurally, neoplastic Leydig cells resemble normal Leydig cells. Surgical ablation is curative for benign Leydig cell tumors.
Adult↗
Purification and characterization of Leydig cells from rat testes.
An LH-responsive Leydig cell preparation (containing 6+/-2% Leydig cells) was obtained by collagenase treatment of rat testis. Centrifugation of this cell preparation through a 13% Ficoll solution for 10 min at 1500 g resulted in a four times purification of the Leydig cells, with a concomitant increases in steroidogenic activity. Addition of 0-2% albumin to the 13% Ficoll solution, adjusted to 280 mosmol/l, resulted in a further twofold purification of the Leydig cells paralleled by a twofold increase in steroidogenic activity. Centrifugation of these Ficoll-albumin-purified Leydig cells through a 6% dextran solution for 2 min at 100 g resulted in a further 1-7 times purification of the Leydig cells. A combination of the two centrifugation steps resulted in a 12-5 times purification of Leydig cells compared with the original crude cell suspension, while an increase in steroidogenic activity of 22-5 times was obtained. This final cell preparation contained 59 +/- 17% Leydig cells (mean +/- S.D., n = 6). The recovery of Leydig cells was 29%. Collagenase treatment of testes deficient in spermatogenesis resulted in a cell preparation with the same steroidogenic activity as Ficoll-purified cells from normal testes. Centrifugation of these cells through a 13% Ficoll solution gave only a limited increase in the steroidogenic activity. Isopycnic centrifugation of the crude cell preparation on a discontinous Ficoll metrizoate gradient resulted in two discrete peaks of Leydig cells, one peak at a density of 1-039-1-055 g/ml and one at a density of 1-068-1-088 g/ml. Both types of cells produced testosterone. In the presence of LH, cyclic AMP production in both types of Leydig cells increased, but testosterone production was only increased by LH in the "denser" Leydig cells and not in the "light" Leydig cells. No difference in sensitivity to LH could be observed between the Leydig cell preparations of different purity. Using a 60 min pre-incubation period the highest testosterone response was obtained with 100-1000 ng LH/ml. The same maximum testosterone response was obtained with 10-100 ng LH/ml when the pre-incubation period was omitted.
Albumins↗
A Leydig cell tumour: a model for the study of lutropin action.
The properties of cells isolated from a Leydig cell tumour have been compared with normal rat testis Leydig cells. These cells were found to be similar in the following respects: 1. Lutropin-stimulated cyclic AMP and testosterone production. 2. Lutropin-activated protein kinase activity followed by phosphorylation of endogenous proteins of mol. wts. 57,000and 14,000. 3. Parallel lutropin dose vs. response curves for phosphorylation of the endogenous proteins and for testosterone production. 4. Two forms of isoenzyme, cyclic AMP dependent protein kinase, present. They differed mainly with respect to the lutropin-stimulated testosterone production, which was much lower in the tumour cells compared with the normal adult testis Leydig cells (4.6 +/- 1.1 and 114 +/- 16 ng testosterone/10(6) cells per 2 h, respectively). However, the lutropin-stimulated steroid production in the tumour cells was quantitatively comparable with the normal rat Leydig cell when the metabolism of pregnenolone in intact cells and mitochondria was inhibited by addition of SU-10603 and/or cyanoketone. It is concluded that the Leydig cell tumour used in this study can be used to investigate certain aspects of lutropin action where large quantities of cells are required.
Animals↗
The influence of activation, removal or denervation of the pineal on the fine structure of the Leydig cell and seminal vesicle epithelium in golden hamsters.
Fine structural changes of testicular interstitial cells of Leydig and secretory cells of seminal vesicles were studied in golden hamsters under different functional states of the pineal gland. Experiments were performed in the reproductive season (summer months). In the hamsters blinded for 8 weeks the testes and the seminal vesicles were markedly atrophic, and the Leydig cells and the secretory cells of seminal vesicles were extremely involuted. By contrast, both types of cells in the pinealectomized or superior cervical ganglionectomized hamsters exhibited cytological features suggestive of an enhanced secretory activity. This study shows that functional activity of Leydig cells as well as secretory cells of seminal vesicles in the hamster may be depressed or augmented by stimulating of inhibiting the pineal antigonadal function, respectively, without performing hypophysectomy or hormonal administration.
Animals↗
Electron microscopy of a feminizing Leydig cell tumor of the testis.
The ultrastructural characteristics of a feminizing interstitial (Leydig) cell tumor of the testis were compared with those of normal Leydig cells and with the findings described in 10 published cases of Leydig cell tumor. The neoplastic Leydig cells superficially resembled normal Leydig cells. Similarities included abundant smooth endoplasmic reticulum, lipid, and microbodies. Contrastingly, Reinke crystalloids and paracrystalline inclusions were absent and lipochrome pigment and lysosomes very rare. The nuclei were large and contained enlarged, often multiple, nucleoli. The nuclear membranes tended to be irregular and undulating. Cytoplasmic membranous whorls and myelin figures were conspicuous. Fairly homogeneous fibrous septa were evident between single and grouped tumor cells. Despite several individual variations, there is a general resemblance between the neoplastic Leydig cells in this patient and those previously reported. No distinguishing ultrastructural characteristics were discerned between feminizing and virilizing Leydig cell tumors.
Adult↗
Changes in fine structure accompanying estrogen-induced tumorigenesis of Leydig cells in the mouse testis.
The development of estrogen-induced Leydig cell tumors in cryptorchid BALB/c mice was studied with the electron microscope. Changes in Leydig cell fine structure are apparent by 10 days after the s.c. implantation of a pellet of diethylstibestrol (DES). The smooth endoplasmic reticulum is diminished, and there is an increase in lipid droplets and free polysomes as compared with untreated cryptochid controls. These alterations persist as the Leydig cells proliferate to form focal areas of hyperplasia in the interstitial tissue. During this period of proliferation, activated macrophages containing large residual bodies appear among the Leydig cells. If DES treatment is continued for several months, malignant Leydig cell tumors, result. They are characterized by a nuclear and cytoplasmic pleomorphism of the Leydig cells and a decreased macrophage population. Virus-like particles are rarely seen within the cell during the period of tumorigenesis. Along with the reduction in smooth endoplasmic reticulum in the Leydig cells after DES treatment, evidence from the literature suggests that there is also a decrease in testosterone biosynthesis. However, it is not clear whether these two effect are correlated, since the level of the microsomal enzymes of steroid biosynthesis may vary independently of either the amount of smooth endoplasmic reticulum or the level of androgen secretion. The increase in lipid droplets seen in Leydig cells after DES treatment suggest the accumulation of precursors from the steroid biosynthetic pathway. The macrophages are though to represent scavenger cells, rather than a primary tumor cell population. The paucity of virus-like particles within altered Leydig cells implies that formed virus is not a prerequisite for tumorigenesis.
Animals↗
Evidence for the involvement of lutropin-independent RNA synthesis in Leydig cell steroidogenesis.
The effect of incubating purified Leydig cells in Eagle's medium and the subsequent effect of the RNA synthesis inhibitors, actinomycin D and cordycepin, on lutropin-stimulated testosterone synthesis have been investigated. The inhibiting effect was found to be inversely related to the time of preincubation; with cells preincubated for 0, 1, 2 and 3 h with Eagle's medium only, followed by 2-h incubation with lutropin with and without actinomycin D, testosterone synthesis was inhibited by 37 +/- 4, 31 +/- 3, 18 +/- 4 and 14 +/- 3% respectively (means +/- s.e.m., n = 5). In cells that had been preincubated for 3 h there was no significant effect of actinomycin D on testosterone synthesis during the first hour of incubation with lutropin. Thereafter the inhibition increased with time reaching a maximum of 30% after 5 h. The effects of preincubation were not due to endogenous lutropin in the Leydig cells because cells isolated from hypophysectomized rats gave similar results. The inhibition of [3H]uridine incorporation into the Leydig cell RNA was 80 +/- 1% with 8 microgram/ml actinomycin D. Increasing the concentration of this inhibitor to 80 microgram/ml did not significantly increase the inhibition of [3H]uridine incorporation or lutropin-stimulated steroidogenesis in preincubated and non-preincubated cells. With cordycepin the inhibition of both RNA synthesis and lutropin-stimulated testosterone synthesis in non-preincubated cells were the same; with 25.1--251 microgram/ml approx. 30--70% resp. With preincubated cells (3 h), 0--50% inhibition of testosterone synthesis was obtained respectively. The inhibitory effect of actinomycin D oimilar to that obtained with lutropin. These observations suggest that during preincubation and independently of lutropin, synthesis of intermediates, including RNAs required for stimulation of steroidogenesis, takes place and that subsequent stimulation of steroidogenesis by lutropin occurs without further de novo RNA synthesis. These results provide evidence for a permissive role of specific RNA and protein synthesis in the action of lutropin on testosterone synthesis in the Leydig cell.
Animals↗
DNA synthesis and DNA polymerase activity in Leydig cells of diethylstilbestrol-stimulated mouse testes.
Using a modification of the collagenase dispersion method of Dufau et al., we examined changes in DNA synthesis produced by estrogens in the interstitial cells of mice that develop malignant Leydig cell tumors after prolonged estrogen administration. Previous work in cryptorchid mice indicated that during continuous estrogen administration [3H]thymidine incorporation into DNA rises to a maximum in 3 to 4 days and then falls to approximately base levels within 2 to 3 weeks. This was confirmed both in Leydig cell concentrates of estrogen-treated mice after either injection with [3H]thymidine or incubation with [3H]thymidine in vitro. This DNA synthesis was blocked by hydroxyurea. DNA synthesis in cells of estrogen-treated BALB/c mice of the Huseby substrain, which have a high incidence of Leydig cell tumors, was 5 to 11 times that in untreated controls. Cells from estrogen-treated C3H/Bi mice, which have a low incidence of Leydig cell tumors, showed only a 2- to 3-fold increase. In the Huseby substrain the rise of DNA synthesis is a peak and subsequent recession were paralleled by a rise and fall in DNA polymerase alpha activity. DNA polymerase beta did not show this variation. In C3H/Bi mice, neither polymerase showed significant change. The evidence suggests that the early estrogen-stimulated DNA synthesis is probably replicative and is associated with increased DNA polymerase alpha activity.
Animals↗
Leydig cell tumor of testis.
In adult patients with Leydig cell tumor of the testis, endocrinologic signs occur in 30 per cent of the cases and often precede the onset of a palpable testicular mass. Gynecomastia is the most common endocrinologic manifestation and probably is due to increased estrogen secretion by the Leydig cells. In the patient with adrenogenital syndrome and testicular enlargement it is difficult to distinguish Leydig cell tumor from adrenal rest hypertrophy. Four patients with Leydig cell tumor and endocrinologic manifestations are discussed; three are adults who presented with gynecomastia and the fourth is a patient with congenital adrenogenital syndrome. In the adult patient inguinal orchiectomy is the treatment of choice, while in the patient with adrenogenital syndrome initial management by high-dose steroid suppression should be attempted prior to testicular exploration.
Adrenal Cortex Neoplasms↗
[Ultrastructure of human heterotopic Leydig cells].
It was demonstrated by light and electron microscopical methods that Leydig cells also exist outside of the testis. In the spermatic cord and near the intraabdominal testicular vessels cells were observed with the characteristics of intratubular Leydig cells. Such characteristics were intranuclear precrystalline inclusions, mitochondria with tubular interior structures and lipid droplets, and a well developed smooth and rough endoplasmatic reticulum. The last two items can be regarded as signs of hormonal activity. The extratesticular Leydig cells in the spermatic cord are located within nerves that contain myelinated axons forming monoaxonal Schwann cell units. Possible they are sensory nerves originating in the receptors of the tunica albuginea. Synapses between axons and heterotopic Leydig cells were not found. The degree of the cytological differentiation leads to the conclusion that these cells may serve, for instance after orchidectomy, as substitutes for the Leydig cells inside the testis.
Humans↗