Interstitial Leydig cell tumorigenesis : leptin and adiponectin signaling in relation to aromatase expression in the human testis

Autor: Malgorzata Kotula-Balak, Izabella Krakowska, Ewelina Gorowska-Wojtowicz, Agnieszka Rak, Malgorzata Brzoskwinia, Bartosz J. Płachno, Barbara Bilińska, Waclaw Tworzydlo, Michal Duliban, Jan Karol Wolski
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Adult
Male
0301 basic medicine
aromatase
medicine.medical_specialty
Carcinogenesis
medicine.drug_class
Estrogen receptor
medicine.disease_cause
leptin
Article
Catalysis
lcsh:Chemistry
Inorganic Chemistry
03 medical and health sciences
0302 clinical medicine
Internal medicine
Lipid droplet
medicine
Humans
Physical and Theoretical Chemistry
Aromatase
Receptor
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
biology
Leydig cell
adiponectin
Organic Chemistry
Leydig Cells
Lipid Droplets
General Medicine
Leydig cell tumor
ultrastructure
Computer Science Applications
030104 developmental biology
Endocrinology
medicine.anatomical_structure
lcsh:Biology (General)
lcsh:QD1-999
Leydig Cell Tumor
Estrogen
030220 oncology & carcinogenesis
biology.protein
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 10
International Journal of Molecular Sciences, Vol 21, Iss 3649, p 3649 (2020)
Popis: 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&ndash
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&ndash
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.
Databáze: OpenAIRE
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