Effects of dexamethasone on steroidogenesis in leydig cells from rats of different ages

Agular, Birte-Marie; Vind, Constance

doi:10.1016/0960-0760(95)00058-8

Cited by 20 publications

(10 citation statements)

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“…The conversion of pregnenolone to progesterone catalysed by 3b-HSD is an important step in Leydig cell steroidogenesis (Tang et al 1998), and it results in the formation of a precursor for testosterone. In support of the present study, evidence can be drawn from the report of Agular and Vind (1995), who have shown that DEX, a synthetic glucocorticoid, diminished the activity of 3b-HSD in Leydig cells from 3, 5, 7, and 10 week old rats. The dose-dependent reduction in the activity of 3b-HSD recorded in the present study may be attributed to the direct genomic (reduction in mRNA expression) and nongenomic (reduction in the availability of co-factor) actions of corticosterone.…”

Section: Discussionsupporting

confidence: 79%

“…An in vitro study has also demonstrated a significant reduction in the activity of 3b-HSD in the Leydig cells of prepubertal, pubertal, and adult rats following a treatment with dexamethasone (DEX), a synthetic glucocorticoid (an analogue of cortisol) (Agular and Vind 1995). However, it is not known whether these changes are due to the defective expression of the genes of 3b-and 17b-HSD.…”

Section: Introductionmentioning

confidence: 97%

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Corticosterone impairs the mRNA expression and activity of 3β- and 17β-hydroxysteroid dehydrogenases in adult rat Leydig cells

Badrinarayanan

Srinivasan

Nithya

et al. 2006

Biochem. Cell Biol.

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Clinical and experimental studies, including our own observations, have shown the adverse effects of excess glucocorticoids on testicular steroid hormone production. The present study was designed to gain insight into the molecular mechanisms by which excess corticosterone impairs Leydig cell steroidogenesis. To achieve this, adult rats were administered with corticosterone-21-acetate (2 mg/100 g body weight) twice daily for 15 days. After the treatment period, rats were killed by decapitation. The testes were removed, decapsulated aseptically and used for the isolation of Leydig cells. Purified Leydig cells were used for assessing the activity of 3beta- and 17beta-hydroxysteroid dehydrogenases (HSDs) and total RNA isolation. For in vitro studies, purified Leydig cells (7.5 x 10(6) cells) of control rats were plated in culture flasks and exposed to different concentrations (50, 100, 200, 400, and 800 nmol/L) of corticosterone for 24 h. At the end of incubation, total RNA was isolated from cultured Leydig cells, and the mRNA of 3beta- and 17beta-HSDs was quantified by RT-PCR. A significant reduction in the activities and levels of 3beta-HSD type-I and 17beta-HSD type-III mRNAs in Leydig cells were observed. In vitro studies demonstrated a dose-dependent significant impairment in both the activity and mRNA expression of these enzymes. These results suggest that corticosterone might have a direct effect on the transcription of the genes of 3beta- and 17beta-HSD. It is inferred from the present in vivo and in vitro studies that one of the molecular mechanisms by which excess corticosterone decreases the steroidogenic potency of Leydig cells is by suppressing the mRNA expression of 3beta-HSD type-I and 17beta-HSD type-III enzymes.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 97%

Corticosterone impairs the mRNA expression and activity of 3β- and 17β-hydroxysteroid dehydrogenases in adult rat Leydig cells

Badrinarayanan

Srinivasan

Nithya

et al. 2006

Biochem. Cell Biol.

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“…Additional studies are necessary to define further the role that glucocorticoids play in the regulation of the glucocorticoid receptor gene expression in the testis. Several studies have shown that the events downstream of the glucocorticoid receptor involve suppression of the LH-induced transcription of steroidogenic enzymes, in particular P450 scc and 3β-HSD (11,33), which are key regulators of testosterone biosynthesis, and also of 17α-hydroxylase/17-20lyase (10,17). It seems unlikely that the above-mentioned mechanism is effective in our present study.…”

Section: Discussionmentioning

confidence: 69%

In vivo inhibition of steroidogenic acute regulatory protein expression by dexamethasone parallels induction of the negative transcription factor DAX-1

2006

Endocr

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In this study, we investigated the effect of dexamethasone on the synthesis of steroidogenic acute regulatory protein (StAR) and the expression of DAX-1 (dosage sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1) and SF-1 (steroidogenic factor-1) in vivo. Male rats were treated with dexamethasone (0.4 and 4 mg/kg body wt per day) by intraperitoneal injections using phosphate-buffered saline as the vehicle for 7 d. At the end of 7 d, serum testosterone levels were decreased. Response to luteinizing hormone (LH) and 8-bromo-cyclic-AMP (8-Br-cAMP) in vitro was reduced in testicular cells isolated from dexamethasone-treated rat testes. Dexamethasone decreased LH-stimulated cAMP production. The conversion of 22(R)-hydroxycholesterol, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, and androstenedione to testosterone was not affected by dexamethasone. Dexamethasone increased DAX-1 expression and concordantly decreased StAR protein and mRNA in testicular cells. The increase in DAX-1 protein corresponded to a 57% reduction in StAR mRNA levels concomitant with a 79% reduction in serum testosterone levels. Dexamethasone had no effect on the level of SF-1, but increased the amount of complexed DAX-1-SF-1. Dexamethasone in vitro suppressed StAR promoter activity when an increasing amount of DAX-1 cDNA was transfected. These results demonstrate that dexamethasone increases expression of DAX-1, which results in increased amounts of complexed DAX-1-SF-1, in the absence of any change in the expression of SF-1. These observations strongly support the concept that dexamethasone suppresses rat testicular testosterone production, at least in part, by increasing the amount of complexed DAX-1-SF-1 in these cells, which leads directly to decreased availability of free SF-1 and, therefore, decreased activation of transcription of the rat StAR gene.

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“…BMP-4, -6 and -7 also lower basal HSD3B mRNA in theca cells (109). Numerous other hormones and growth factors negatively impact 3b-HSD protein levels or enzymatic activity in gonadal cells including glucocorticoids (328)(329)(330)(331), but their effects on HSD3B mRNA are not characterized.…”

Section: Hormonal Control Of Hsd3b Gene Expressionmentioning

confidence: 97%

Transcriptional Regulation of Steroidogenic Genes: STARD1, CYP11A1 and HSD3B

LaVoie

King

2009

Exp Biol Med (Maywood)

221

159

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Expression of the genes that mediate the first steps in steroidogenesis, the steroidogenic acute regulatory protein (STARD1), the cholesterol side-chain cleavage enzyme, cytochrome P450scc (CYP11A1) and 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase (HSD3B), is tightly controlled by a battery of transcription factors in the adrenal cortex, the gonads and the placenta. These genes generally respond to the same hormones that stimulate steroid production through common pathways such as cAMP signaling and common actions on their promoters by proteins such as NR5A and GATA family members. However, there are distinct temporal, tissue and species-specific differences in expression between the genes that are defined by combinatorial regulation and unique promoter elements. This review will provide an overview of the hormonal and transcriptional regulation of the STARD1, CYP11A1 and specific steroidogenic HSD3B genes in the adrenal, testis, ovary and placenta and discuss the current knowledge regarding the key transcriptional factors involved.

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Effects of dexamethasone on steroidogenesis in leydig cells from rats of different ages

Cited by 20 publications

References 34 publications

Corticosterone impairs the mRNA expression and activity of 3β- and 17β-hydroxysteroid dehydrogenases in adult rat Leydig cells

Corticosterone impairs the mRNA expression and activity of 3β- and 17β-hydroxysteroid dehydrogenases in adult rat Leydig cells

In vivo inhibition of steroidogenic acute regulatory protein expression by dexamethasone parallels induction of the negative transcription factor DAX-1

Transcriptional Regulation of Steroidogenic Genes: STARD1, CYP11A1 and HSD3B

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