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

Michał Duliban , E. Gorowska-Wojtowicz , Wacław Tworzydło , Agnieszka Rak , Małgorzata Brzoskwinia , Izabella Krakowska , J.K. Wolski , Małgorzata Kotula-Balak , B. J. Płachno , Barbara Bilinska

Abstract

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.
Author Michał Duliban
Michał Duliban,,
-
, E. Gorowska-Wojtowicz
E. Gorowska-Wojtowicz,,
-
, Wacław Tworzydło
Wacław Tworzydło,,
-
, Agnieszka Rak
Agnieszka Rak,,
-
, Małgorzata Brzoskwinia
Małgorzata Brzoskwinia,,
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, Izabella Krakowska
Izabella Krakowska,,
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, J.K. Wolski
J.K. Wolski,,
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, Małgorzata Kotula-Balak (VET)
Małgorzata Kotula-Balak,,
- University Centre for Veterinary Medicine UJ-UR
, B. J. Płachno
B. J. Płachno,,
-
, Barbara Bilinska
Barbara Bilinska,,
-
Journal seriesInternational Journal of Molecular Sciences, ISSN 1422-0067, (N/A 140 pkt)
Issue year2020
Vol21
No10
Pages3649
ASJC Classification1604 Inorganic Chemistry; 1605 Organic Chemistry; 1606 Physical and Theoretical Chemistry; 1706 Computer Science Applications; 1607 Spectroscopy; 1312 Molecular Biology; 2700 General Medicine; 1503 Catalysis
DOIDOI:10.3390/ijms21103649
Languageen angielski
Score (nominal)140
Score sourcejournalList
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.224; WoS Impact Factor: 2018 = 4.183 (2) - 2018=4.331 (5)
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