Flutamide Alters the Expression of Chemerin, Apelin, and Vaspin and Their Respective Receptors in the Testes of Adult Rats

Małgorzata Brzoskwinia , Laura Pardyak , Agnieszka Rak , Alicja Kamińska , Anna Hejmej , S. Marek , Małgorzata Kotula-Balak , Barbara Bilinska

Abstract

Adipokines influence energy metabolism and have effects on male reproduction, including spermatogenesis and/or Sertoli cell maturation; however, the relationship between these active proteins and androgens in testicular cells is limited. Here, we studied the impact of short-term exposure to flutamide (an anti-androgen that blocks androgen receptors) on the expression of chemerin, apelin, vaspin and their receptors (CCRL2, CMKLR1, GPR1, APLNR, GRP78, respectively) in adult rat testes. Moreover, the levels of expression of lipid metabolism-modulating proteins (PLIN1, perilipin1; TSPO, translocator protein) and intercellular adherens junction proteins (nectin-2 and afadin) were determined in testicular cells. Plasma levels of adipokines, testosterone and cholesterol were also evaluated. Gene expression techniques used included the quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB) and immunohistochemistry (IHC). The androgen-mediated effects observed post-flutamide treatment were found at the gonadal level as chemerin, apelin, and vaspin gene expression alterations at mRNA and protein levels were detected, whereas the cellular targets for these adipokines were recognised by localisation of respective receptors in testicular cells. Plasma concentrations of all adipokines were unchanged, whereas plasma cholesterol content and testosterone level increased after flutamide exposure. Differential distribution of adipokine receptors indicates potential para- or autocrine action of the adipokines within the rat testes. Additionally, changes in the expression of PLIN1 and TSPO, involved in the initial step of testosterone synthesis in Leydig cells, suggest that testicular cells represent a target of flutamide action. Increase in the gene expression of PLIN1 and TSPO and higher total plasma cholesterol content indicates enhanced availability of cholesterol in Leydig cells as a result of androgen-mediated effects of flutamide. Alterations in adherens junction protein expression in the testis confirm the flutamide efficacy in disruption of androgen signalling and presumably lead to impaired para- and autocrine communication, important for proper functioning of adipokines.
Author Małgorzata Brzoskwinia
Małgorzata Brzoskwinia,,
-
, Laura Pardyak
Laura Pardyak,,
-
, Agnieszka Rak
Agnieszka Rak,,
-
, Alicja Kamińska
Alicja Kamińska,,
-
, Anna Hejmej
Anna Hejmej,,
-
, S. Marek
S. Marek,,
-
, Małgorzata Kotula-Balak (VET)
Małgorzata Kotula-Balak,,
- University Centre for Veterinary Medicine UJ-UR
, Barbara Bilinska
Barbara Bilinska,,
-
Journal seriesInternational Journal of Molecular Sciences, ISSN 1422-0067, (N/A 140 pkt)
Issue year2020
Vol21
No12
Pages4439
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/ijms21124439
Languageen angielski
Score (nominal)140
Score sourcejournalList
Publication indicators 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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