Molecular adaptations of testosterone-producing Leydig cells during systemic in vivo blockade of the androgen receptor

被引:13
作者
Bjelic, Maja M. [1 ]
Stojkov, Natasa J. [1 ]
Baburski, Aleksandar Z. [1 ]
Sokanovic, Srdjan J. [1 ]
Mihajlovic, Aleksandar I. [1 ]
Janjic, Marija M. [1 ]
Kostic, Tatjana S. [1 ]
Andric, Silvana A. [1 ]
机构
[1] Univ Novi Sad, Fac Sci, Dept Biol & Ecol, Reprod Endocrinol & Signaling Grp, Novi Sad 21000, Serbia
关键词
Leydig cells; Testosterone; Androcur; Steroidogenic machinery; cAMP signaling; REGULATORY PROTEIN EXPRESSION; TESTICULAR INTERSTITIAL FLUID; RNA HELICASE GRTH/DDX25; STEROIDOGENIC MACHINERY; MITOCHONDRIAL PROTEIN; MEDIATED REGULATION; ANABOLIC THERAPIES; NITRIC-OXIDE; TUMOR-CELLS; HORMONE;
D O I
10.1016/j.mce.2014.08.007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
This study systematically evaluates the effects of androgen receptor (AR) blockade on molecular events in Leydig cells. Results showed that intramuscular administration of testosterone-enanthate, at clinically relevant dose, decreased testosterone in interstitial fluid and Leydig cells from adult rats. AR-blocker (Androcur) prevented this effect and testosterone-reduced Leydig cells steroidogenic capacity/activity. Testosterone-reduced expression of some steroidogenic enzymes/proteins (Tspo,StAR,Hsd3b1/2) and transcription factors (Nur77,Gata4,Dax1) was completely abrogated, while decreased expression of Star,Cyp11a1,Cyp17a1,Hsd17b4,Creb1a was partially prevented. In the same cells, increased expression of Hsd3b5/HSD3B and Ar/AR was abolished. Androcur-treatment abolished testosterone-reduced cAMP, coupled with a changed expressional milieu of cAMP signaling elements. Results from in vitro experiments suggest that some of these effects are testosterone-AR dependent, while others could be due to disturbed LH and/or other signals. Presented data provide new molecular insight into Leydig cells function and are important in terms of human reproductive health and the wide-spread use of Androcur as well as use/abuse of testosterone-enanthate. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
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页码:10 / 25
页数:16
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