Acephate interferes with androgen synthesis in rat immature Leydig cells.
8-Bromo Cyclic Adenosine Monophosphate
/ analogs & derivatives
Androgens
/ metabolism
Animals
Apoptosis
/ drug effects
Cells, Cultured
Leydig Cells
/ drug effects
Luteinizing Hormone
/ antagonists & inhibitors
Male
Multienzyme Complexes
/ antagonists & inhibitors
Organothiophosphorus Compounds
/ pharmacology
Phosphoramides
/ pharmacology
Progesterone
/ pharmacology
Progesterone Reductase
/ antagonists & inhibitors
Rats
Rats, Sprague-Dawley
Receptors, LH
/ antagonists & inhibitors
Steroid Isomerases
/ antagonists & inhibitors
Testis
/ drug effects
3β-hydroxysteroid dehydrogenase isoform 1
Acephate
Luteinizing hormone receptor
Rat immature Leydig cells
Steroidogenesis
Steroidogenic enzymes
Journal
Chemosphere
ISSN: 1879-1298
Titre abrégé: Chemosphere
Pays: England
ID NLM: 0320657
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
19
09
2019
revised:
29
11
2019
accepted:
08
12
2019
pubmed:
22
12
2019
medline:
14
4
2020
entrez:
22
12
2019
Statut:
ppublish
Résumé
Acephate is an organophosphate pesticide. It is widely used. However, whether it inhibits androgen synthesis and metabolism remains unclear. In the current study, we investigated the effect of acephate on the inhibition of androgen synthetic and metabolic pathways in rat immature Leydig cells after 3-h culture. Acephate inhibited basal androgen output in a dose-dependent manner with the inhibition starting at 0.5 μM. It significantly inhibited luteinizing hormone and 8-Br-cAMP stimulated androgen output at 50 μM. It significantly inhibited progesterone-mediated androgen output at 50 μM. Further study demonstrated that acephate down-regulated the expression of Hsd3b1 and its protein at ≥ 0.5 μM, Lhcgr at 5 μM and Star at 50 μM. Acephate directly blocked rat testicular HSD3B1 activity at 50 μM. Acephate did not affect other androgen synthetic and metabolic enzyme activities as well as ROS production, proliferation, and apoptosis of immature Leydig cells. In conclusion, acephate targets LHCGR, STAR, and HSD3B1, thus blocking androgen synthesis in rat immature Leydig cells and HSD3B1 is being the most sensitive target of acephate.
Identifiants
pubmed: 31864041
pii: S0045-6535(19)32837-1
doi: 10.1016/j.chemosphere.2019.125597
pii:
doi:
Substances chimiques
Androgens
0
LHCGR protein, rat
0
Multienzyme Complexes
0
Organothiophosphorus Compounds
0
Phosphoramides
0
Receptors, LH
0
8-Bromo Cyclic Adenosine Monophosphate
23583-48-4
acephate
3Y417O444D
Progesterone
4G7DS2Q64Y
Luteinizing Hormone
9002-67-9
8-chloro-cyclic adenosine monophosphate
BQ94Z7E5OR
Progesterone Reductase
EC 1.1.1.145
Hsd3b1 protein, rat
EC 5.3.3.-
Steroid Isomerases
EC 5.3.3.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
125597Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest No conflict of interest is declared.