TY - JOUR
T1 - Acute effects of the translocator protein drug ligand FGIN-1-27 on serum testosterone and luteinizing hormone levels in male Sprague-Dawley rats
AU - Chen, Fenfen
AU - Lu, Hemin
AU - Chen, Panpan
AU - Zhao, Xingxing
AU - Guan, Xiaojui
AU - Liang, Qingquan
AU - Zirkin, Barry R.
AU - Ye, Leping
AU - Chen, Haolin
N1 - Funding Information:
1Department of Gynaecology and Obstetrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; 2Department of Anesthesiology, Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; 3Department of Pediatrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; 4Zhejiang Province Key Lab of Anesthesiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China and 5Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA ∗Correspondence: Department of Pediatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Western Xueyuan Road, Wenzhou, Zhejiang 325027, China. E-mail: yeleping@163.com (LY); Department of Gynaecology and Obstetrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Western Xueyuan Road, Wenzhou, Zhejiang 325027, China. E-mail: hchen13@jhu.edu (HC) †Grant Support: This work was supported by Natural Science Foundation of China Grants 81771635 (LP), 81471411(HC), and 81741041(HC); Natural Science Foundation of Zhejiang Province grant LY17H040012 (HC); Wenzhou City Public Welfare Science and Technology Project Y20150012 (HC); and NIH grant R01 AG021092 (BZ). ‡FC and HL contributed equally to the work. Edited by Dr. T. Rajendra Kumar, PhD, University of Colorado Anschutz Medical Campus
Publisher Copyright:
© 2018 The Author(s).
PY - 2019/3/1
Y1 - 2019/3/1
N2 - We reported that FGIN-1-27 (N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide, FGIN), a synthetic ligand for translocator protein (TSPO, 18 kDa), increased serum testosterone levels in young and aged Brown Norway rats after its administration daily for 10 days. It is not known, however, how soon after treatment with FGIN serum testosterone rises, how long levels remain elevated after cessation of treatment, or whether the drug acts solely through TSPO. Adult Sprague-Dawley male rats received a single ip dose of FGIN (1 mg/kg BW). Serial blood samples were collected, and serum testosterone and luteinizing hormone (LH) were assessed hourly throughout 24 h. Testosterone concentration was maximal by 3 h, remained significantly higher than the controls at 10 h, and returned to the control level by 24 h. Consistent with the in vivo study, culturing isolated Leydig cells with either FGIN (40 μM) or LH (0.1 ng/ml) resulted in significantly increased testosterone production by 30 min, and the stimulatory effects persisted through 48 h. At a very early (15 min) treatment time, however, FGIN significantly increased testosterone production but LH had not yet done so. Surprisingly, in vivo treatment with FGIN not only increased serum testosterone but also serum LH concentration, raising the possibility that FGIN may increase serum testosterone concentration by dual mechanisms.
AB - We reported that FGIN-1-27 (N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide, FGIN), a synthetic ligand for translocator protein (TSPO, 18 kDa), increased serum testosterone levels in young and aged Brown Norway rats after its administration daily for 10 days. It is not known, however, how soon after treatment with FGIN serum testosterone rises, how long levels remain elevated after cessation of treatment, or whether the drug acts solely through TSPO. Adult Sprague-Dawley male rats received a single ip dose of FGIN (1 mg/kg BW). Serial blood samples were collected, and serum testosterone and luteinizing hormone (LH) were assessed hourly throughout 24 h. Testosterone concentration was maximal by 3 h, remained significantly higher than the controls at 10 h, and returned to the control level by 24 h. Consistent with the in vivo study, culturing isolated Leydig cells with either FGIN (40 μM) or LH (0.1 ng/ml) resulted in significantly increased testosterone production by 30 min, and the stimulatory effects persisted through 48 h. At a very early (15 min) treatment time, however, FGIN significantly increased testosterone production but LH had not yet done so. Surprisingly, in vivo treatment with FGIN not only increased serum testosterone but also serum LH concentration, raising the possibility that FGIN may increase serum testosterone concentration by dual mechanisms.
KW - FGIN-1-27
KW - LH
KW - Leydig cell
KW - Testosterone
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U2 - 10.1093/biolre/ioy220
DO - 10.1093/biolre/ioy220
M3 - Article
C2 - 30299464
AN - SCOPUS:85063930548
SN - 0006-3363
VL - 100
SP - 824
EP - 832
JO - Biology of reproduction
JF - Biology of reproduction
IS - 3
ER -