scholarly journals Towards understanding biology of leydiogioma. G protein-coupled receptor and peroxisome proliferator-activated receptor crosstalk regulates lipid metabolism and steroidogenesis in Leydig cell tumors

2018 ◽  
Author(s):  
Malgorzata Kotula-Balak ◽  
Ewelina Gorowska-Wojtowicz ◽  
Agnieszka Milon ◽  
Piotr Pawlicki ◽  
Alicja Kaminska ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Leydig Cell ◽  
Balance Control ◽  
Regulatory Protein ◽  
Hormone Sensitive Lipase ◽  
Cholesterol Concentration ◽  
Peroxisome Proliferator ◽  
Mouse Tumor ◽  
Lipid Balance ◽  
Leydig Cell Tumors

AbstractLeydig cell tumors (LCT) are the most common type of testicular sex cord-stromal tumor. In this report, we implicate the G-coupled estrogen receptor (GPER) and peroxisome proliferator receptor (PPAR) in regulation of lipid homeostasis and the expression of steroidogenesis-controlling molecules in clinical specimens of LCTs and cell line (mouse tumor Leydig cells; MA-10). We also show the general structure and morphology of human LCTs with the use of scanning electron microscopy and light microscopy, respectively. In LCTs, protein immunoblotting and immunohistochemical analysis revealed increased expression of GPER and decreased expression of PPARα, β and γ. Concomitantly, changes in expression pattern of the lutropin receptor (LHR), protein kinase A (PKA), perilipin (PLIN), hormone sensitive lipase (HSL), steroidogenic acute regulatory protein (StAR), translocator protein (TSPO), HMG-CoA synthase (HMGCA), and HMG-CoA reductase (HMGCR) were observed.Using MA-10 cells treated with GPER and PPAR antagonists (alone and in combination), we demonstrated there is a GPER-PPAR mediated control of cholesterol concentration. In addition, GPER-PPARα regulated estradiol secretion, while GPER-PPARγ affected cGMP concentration. It is assumed that GPER and PPAR can be altered in LCT, resulting in a perturbed lipid balance and steroidogenesis. In LCTs, the phosphatidylinositol-3-kinase (PI3K)-Akt-mTOR signaling pathway was disturbed. Thus, PI3K-Akt-mTOR, together with cGMP, can play a role in LCT proliferation, growth, and metastasis as well as lipid balance control.In conclusion, we discuss the implications of GPER-PPAR interaction with lipid metabolism and steroidogenesis controlling-molecules in LCT biology that can be used in future studies as potential targets of diagnostic and therapeutic implementations.

scholarly journals Interstitial Leydig Cell Tumorigenesis—Leptin and Adiponectin Signaling in Relation to Aromatase Expression in the Human Testis

2020 ◽  
Vol 21 (10) ◽  
pp. 3649 ◽  
Author(s):  
Michal Duliban ◽  
Ewelina Gorowska-Wojtowicz ◽  
Waclaw Tworzydlo ◽  
Agnieszka Rak ◽  
Malgorzata Brzoskwinia ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Molecular Mechanisms ◽  
Lipid Homeostasis ◽  
Human Testis ◽  
Interstitial Tissue ◽  
Electron Microscopic ◽  
Biochemical Characteristics ◽  
Estrogen Level ◽  
Lipid Balance ◽  
Leydig Cell Tumors

Although epidemiological studies from the last years report an increase in the incidences of Leydig cell tumors (previously thought to be a rare disease), the biochemical characteristics of that tumor important for understanding its etiology, diagnosis, and therapy still remains not completely characterized. Our prior studies reported G-protein coupled estrogen receptor signaling and estrogen level disturbances in Leydig cell tumors. In addition, we found that expressions of multi-level-acting lipid balance- and steroidogenesis–controlling proteins including peroxisome proliferator-activated receptor are altered in this tumor. In order to get deeper into the other molecular mechanisms that regulate lipid homeostasis in the Leydig cell tumor, here we investigate the presence and expression of newly-described hormones responsible for lipid homeostasis balancing (leptin and adiponectin), together with expression of estrogen synthase (aromatase). Samples of Leydig cell tumors (n = 20) were obtained from patients (31–45 years old) and used for light and transmission electron microscopic, western blotting, and immunohistochemical analyses. In addition, body mass index (BMI) was calculated. In tumor mass, abundant lipid accumulation in Leydig cells and various alterations of Leydig cell shape, as well as the presence of adipocyte-like cells, were observed. Marked lipid content and various lipid droplet size, especially in obese patients, may indicate alterations in lipid homeostasis, lipid processing, and steroidogenic organelle function in response to interstitial tissue pathological changes. We revealed significantly increased expression of leptin, adiponectin and their receptors, as well as aromatase in Leydig cell tumors in comparison to control. The majority of patients (n = 13) were overweight as indicated by their BMI. Moreover, a significant increase in expression of phospholipase C (PLC), and kinases Raf, ERK which are part of adipokine transductional pathways, was demonstrated. These data expand our previous findings suggesting that in human Leydig cell tumors, estrogen level and signaling, together with lipid status, are related to each other. Increased BMI may contribute to certain biochemical characteristics and function of the Leydig cell in infertile patients with a tumor. In addition, altered adipokine-estrogen microenvironment can have an effect on proliferation, growth, and metastasis of tumor cells. We report here various targets (receptors, enzymes, hormones) controlling lipid balance and estrogen action in Leydig cell tumors indicating their possible usefulness for diagnostics and therapy.

Transcriptional adaptations of lipid metabolism in tibialis anterior muscle of endurance-trained athletes

2003 ◽  
Vol 15 (2) ◽  
pp. 148-157 ◽  
Author(s):  
Beat Schmitt ◽  
Martin Flück ◽  
Jacques Décombaz ◽  
Roland Kreis ◽  
Chris Boesch ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Mrna Level ◽  
Hormone Sensitive Lipase ◽  
Moderate Intensity ◽  
Resonance Spectroscopy ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Fatty Acid Binding

It was hypothesized that transcriptional reprogramming is involved in the structural and functional adaptations of lipid metabolism in human tibialis anterior muscle (TA) from endurance-trained male subjects. RT-PCR experiments demonstrated a significant upregulation of the mRNA level of key enzymes involved in 1) lipolytic mobilization of fatty acids (FA) from intramyocellular lipid (IMCL) stores via hormone-sensitive lipase (LIPE), 2) intramyocellular FA transport via muscle fatty acid binding protein (FABP3), and 3) oxidative phosphorylation (cytochrome c oxidase I, COI), in TA of endurance-trained vs. untrained subjects. In contrast, mRNAs for factors involved in glycolysis (muscle 6-phosphofructokinase, PFKM), intramyocellular storage of FA (diacylglycerol O-acyltransferase 1, DGAT), and β-oxidation (long-chain acyl-coenzyme A dehydrogenase, ACADL) were invariant between TA of trained and untrained subjects. Correlation analysis identified an association of LIPE with FABP3 and LPL (lipoprotein lipase) mRNA levels and indicated coregulation of the transcript level for LIPE, FABP3, and COI with the level of mRNA encoding peroxisome proliferator-activated receptor-α (PPAR-α), the master regulator of lipid metabolism. Moreover, a significant correlation existed between LPL mRNA and the absolute rate of IMCL repletion determined by magnetic resonance spectroscopy after exhaustive exercise. Additionally, the LIPE mRNA level correlated with ultrastructurally determined IMCL content and mitochondrial volume density. The present data point to a training-induced, selective increase in mRNA levels of enzymes which are involved in metabolization of intramuscular FA, and these data confirm the well-established phenomenon of enhanced lipid utilization during exercise at moderate intensity in muscles of endurance-trained subjects.

Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK

2010 ◽  
Vol 298 (4) ◽  
pp. C961-C971 ◽  
Author(s):  
Mandeep P. Gaidhu ◽  
Nicole M. Anthony ◽  
Prital Patel ◽  
Thomas J. Hawke ◽  
Rolando B. Ceddia
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Adrenergic Receptor ◽  
Molecular Mechanisms ◽  
Citrate Synthase ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Receptor Signaling ◽  
High Fat ◽  
Fat Depots

This study investigated the molecular mechanisms by which a high-fat diet (HFD) dysregulates lipolysis and lipid metabolism in mouse epididymal (visceral, VC) and inguinal (subcutaneous, SC) adipocytes. Eight-weeks of HFD feeding increased adipose triglyceride lipase (ATGL) content and comparative gene identification-58 (CGI-58) expression, whereas hormone-sensitive lipase (HSL) phosphorylation and perilipin content were severely reduced. Adipocytes from HFD mice elicited increased basal but blunted epinephrine-stimulated lipolysis and increased diacylglycerol content in both fat depots. Consistent with impaired adrenergic receptor signaling, HFD also increased adipose-specific phospholipase A2 expression in both fat depots. Inhibition of E-prostanoid 3 receptor increased basal lipolysis in control adipocytes but failed to acutely alter the effects of HFD on lipolysis in both fat depots. In HFD visceral adipocytes, activation of adenylyl cyclases by forskolin increased HSL phosphorylation and surpassed the lipolytic response of control cells. However, in HFD subcutaneous adipocytes, forskolin induced lipolysis without detectable HSL phosphorylation, suggesting activation of an alternative lipase in response to HFD-induced suppression of HSL in VC and SC adipocytes. HFD also powerfully inhibited basal, epinephrine-, and forskolin-induced AMP kinase (AMPK) activation as well peroxisome proliferator-activated receptor gamma coactivator-1α expression, citrate synthase activity, and palmitate oxidation in both fat depots. In summary, novel evidence is provided that defective adrenergic receptor signaling combined with upregulation of ATGL and suppression of HSL and AMPK signaling mediate HFD-induced alterations in lipolysis and lipid utilization in VC and SC adipocytes, which may play an important role in defective lipid mobilization and metabolism seen in diet-induced obesity.

scholarly journals TERT Gene Fusions Characterize a Subset of Metastatic Leydig Cell Tumors

2021 ◽  
Author(s):  
Bozo Kruslin ◽  
Zoran Gatalica ◽  
Ondrej Hes ◽  
Faruk Skenderi ◽  
Markku Miettinen ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Gene Fusions ◽  
Tert Gene ◽  
Leydig Cell Tumors

Peroxisome Proliferator-Activated Receptors and Lipid Metabolism

1993 ◽  
Vol 684 (1 Zinc-Finger P) ◽  
pp. 157-173 ◽  
Author(s):  
HANSJÖRG KELLER ◽  
ABDERRAHIM MAHFOUDI ◽  
CHRISTINE DREYER ◽  
ABDELMADJID K. HIHI ◽  
JEFFREY MEDIN ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors

LEYDIG CELL TUMORS PRESENTING AS AZOOSPERMIA

1999 ◽  
Vol 161 (5) ◽  
pp. 1571-1572 ◽  
Author(s):  
MARK L. FALLICK ◽  
WILLIAM W. LIN ◽  
LARRY I. LIPSHULTZ
Keyword(s):  
Leydig Cell ◽  
Leydig Cell Tumors
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