Dexamethasone suppresses the differentiation of stem Leydig cells in rats in vitro.
Animals
Cell Differentiation
/ drug effects
Dexamethasone
/ toxicity
Gene Expression
/ drug effects
Glucocorticoids
/ toxicity
Leydig Cells
/ drug effects
Male
Rats, Sprague-Dawley
Receptors, Glucocorticoid
/ genetics
Scavenger Receptors, Class B
/ genetics
Stem Cells
/ drug effects
Steroid 17-alpha-Hydroxylase
/ genetics
Dexamethasone
Differentiation
Glucocorticoid
Proliferation
Stem Leydig cells
Testosterone
Journal
BMC pharmacology & toxicology
ISSN: 2050-6511
Titre abrégé: BMC Pharmacol Toxicol
Pays: England
ID NLM: 101590449
Informations de publication
Date de publication:
27 05 2019
27 05 2019
Historique:
received:
13
10
2018
accepted:
09
05
2019
entrez:
29
5
2019
pubmed:
28
5
2019
medline:
31
1
2020
Statut:
epublish
Résumé
It is an established fact that excess of glucocorticoids could cause the harmful effects, such as suppression on the male reproduction. Although glucocorticoids pharmacologically inhibit the Leydig cell function, their roles in Leydig cell development are unclear. Therefore, the present study was designed to investigate effects of synthetic glucocorticoid dexamethasone (DEX) on rat stem Leydig cell proliferation and differentiation. Male Sprague-Dawley rats received a single intraperitoneal injection of 75 mg/kg EDS to eliminate Leydig cells and an in vitro culture system of the seminiferous tubules was established from Leydig cell-depleted testis. Using basal medium and Leydig cell differentiation-inducing medium (LIM) in the culture system, we examined the effects of DEX (0-100 nM) on the proliferation and differentiation of the stem Leydig cells in vitro, respectively. Results showed that LIM is a good agent to induce stem Leydig cell differentiation into Leydig cells that produce testosterone in vitro. DEX inhibited the differentiation of stem Leydig cells by reducing the expression levels of Cyp17a1 and Scarb1 and that NR3C1 antagonist RU38486 reversed the DEX-mediated effects. However, DEX are not involved with the proliferation of stem Leydig cells. DEX suppressed the differentiation of rat Leydig cells in vitro and glucocorticoid-induced effects acted through NR3C1. This suppression partially targets on Cyp17a1 and Scarb1 gene expression.
Sections du résumé
BACKGROUND
It is an established fact that excess of glucocorticoids could cause the harmful effects, such as suppression on the male reproduction. Although glucocorticoids pharmacologically inhibit the Leydig cell function, their roles in Leydig cell development are unclear. Therefore, the present study was designed to investigate effects of synthetic glucocorticoid dexamethasone (DEX) on rat stem Leydig cell proliferation and differentiation.
METHODS
Male Sprague-Dawley rats received a single intraperitoneal injection of 75 mg/kg EDS to eliminate Leydig cells and an in vitro culture system of the seminiferous tubules was established from Leydig cell-depleted testis. Using basal medium and Leydig cell differentiation-inducing medium (LIM) in the culture system, we examined the effects of DEX (0-100 nM) on the proliferation and differentiation of the stem Leydig cells in vitro, respectively.
RESULTS
Results showed that LIM is a good agent to induce stem Leydig cell differentiation into Leydig cells that produce testosterone in vitro. DEX inhibited the differentiation of stem Leydig cells by reducing the expression levels of Cyp17a1 and Scarb1 and that NR3C1 antagonist RU38486 reversed the DEX-mediated effects. However, DEX are not involved with the proliferation of stem Leydig cells.
CONCLUSIONS
DEX suppressed the differentiation of rat Leydig cells in vitro and glucocorticoid-induced effects acted through NR3C1. This suppression partially targets on Cyp17a1 and Scarb1 gene expression.
Identifiants
pubmed: 31133074
doi: 10.1186/s40360-019-0312-z
pii: 10.1186/s40360-019-0312-z
pmc: PMC6537393
doi:
Substances chimiques
Glucocorticoids
0
NR3C1 protein, rat
0
Receptors, Glucocorticoid
0
Scarb1 protein, rat
0
Scavenger Receptors, Class B
0
Dexamethasone
7S5I7G3JQL
CYP17A1 protein, rat
EC 1.14.14.19
Steroid 17-alpha-Hydroxylase
EC 1.14.14.19
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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