Dexamethasone acutely regulates endocrine parameters in stallions and subsequently affects gene expression in testicular germ cells

Ing, Nancy H.; Brinsko, Steven P.; Curley, K.O.; Forrest, D.W.; Love, Charles C.; Hinrichs, Katrin; Vogelsang, M.M.; Varner, D.D.; Welsh, T. H.

doi:10.1016/j.anireprosci.2014.11.007

Cited by 10 publications

(8 citation statements)

References 32 publications

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“…In the present investigation, DEX caused dramatic alterations in the histological structure of testes and a marked decline in the level of testosterone, and these results were in harmony with previous reports for DEX‐induced animals (Gao et al., , & Ing et al., ). These disturbances may be due to the inhibition of gonadotropin secretion, excessive oxidative stress and the degeneration of Leydig cells (Chen, Wang, Wang, Gao, & Zhang, ; Jeje, Akindele, Balogun, & Raji, ; Yun, Ji‐Yeon, & Myoung, ).…”

Section: Discussionsupporting

confidence: 94%

Grape seed extract attenuates dexamethasone‐induced testicular and thyroid dysfunction in male albino rats

Hasona

2018

Andrologia

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This study scrutinised the ameliorative properties of grape seed extract (GSE) in dexamethasone (DEX)-induced testicular and thyroid dysfunction associated with oxidative stress in male albino rats. Thirty-two healthy adult male albino rats were divided into four groups of eight animals each: normal, DEX control, DEX + GSE (200 mg/kg body weight) group and DEX + GSE (400 mg/kg body weight) group. The body weight gain and testes weight were assessed. Plasma testosterone and thyroid profile were determined. Testicular glucose-6-phosphate dehydrogenase (G-6-PDH), acid phosphatase (ACP), total protein and glutathione (GSH) levels, as well as catalase (CAT) activity also histopathological changes of the testis were evaluated. DEX treatment caused a significant decrease in body weight gain and weight of testes. Significant alterations in enzymatic and nonenzymatic antioxidants were observed. Moreover, a marked reduction in plasma testosterone levels and thyroid profile was observed. The administration of GSE significantly attenuated the deleterious effects of oxidative stress induced by DEX, as well as attenuated DEX-induced testicular and thyroid damage. Furthermore, DEX induced histological alterations in the testis. GSE ameliorated the injurious effects of DEX and improved the histological alterations in the testis.

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Section: Discussionsupporting

confidence: 94%

Grape seed extract attenuates dexamethasone‐induced testicular and thyroid dysfunction in male albino rats

Hasona

2018

Andrologia

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“…Evaluation of these recombinant enzymes will enable quantitative comparisons of the steroid isomerase activities among the species investigated, and allow further investigation of the effects of endogenous compounds like follicle stimulating hormone, luteinizing hormone, testosterone, estradiol, and glucocorticoids, as well as pharmaceuticals like phenobarbital or dexamethasone on the expression of the enzyme. For instance, expression of the GSTA3 gene was down-regulated along with testosterone synthesis in testes of stallions treated with dexamethasone [18,19]. In cultured porcine Sertoli cells, follicle stimulating hormone, testosterone and estradiol increased GSTA gene expression [24].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, transfection of such a cell line with two different small interfering RNAs both decreased progesterone synthesis by 26%. In stallions treated with dexamethasone, a glucocorticoid drug used to treat inflammation, testicular levels of GSTA3 mRNAs decreased by 50% at 12 hours post-injection, concurrent with a 94% reduction in serum testosterone [18,19]. In stallion testes and cultured Leydig cells, dexamethasone also decreased concentrations of steroidogenic factor 1 (SF1) mRNA [20].…”

Section: Introductionmentioning

confidence: 99%

Conservation of glutathione S-transferase mRNA and protein sequences similar to human and horse Alpha class GST A3-3 across dog, goat, and opossum species

Lindström

et al. 2020

Preprint

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Recently, the glutathione S-transferase A3-3 (GST A3-3) homodimeric enzyme was identified as the most efficient enzyme that catalyzes isomerization of the precursors of testosterone, estradiol, and progesterone in the gonads of humans and horses. However, the presence of GST A3-3 orthologs with equally high ketosteroid isomerase activity has not been verified in other mammalian species, even though pig and cattle homologs have been cloned and studied. Identifying GSTA3 genes is a challenge because of multiple GSTA gene duplications (12 in the human genome), so few genomes have a corresponding GSTA3 gene annotated. To improve our understanding of GSTA3 gene products and their functions across diverse mammalian species, we cloned homologs of the horse and human GSTA3 mRNAs from the testes of a dog, goat, and gray short-tailed opossum, with those current genomes lacking GSTA3 gene annotations. The resultant novel GSTA3 mRNA and inferred protein sequences had a high level of conservation with human GSTA3 mRNA and protein sequences (≥ 70% and ≥ 64% identities, respectively). Sequence conservation was also apparent for the 13 residues of the “H-site” in the 222 amino acid GSTA3 protein that is known to interact with the steroid substrates. Modeling predicted that the dog GSTA3-3 is a more active ketosteroid isomerase than the goat or opossum enzymes. Our results help us understand the active sites of mammalian GST A3-3 enzymes, and their inhibitors may be useful for reducing steroidogenesis for medical purposes, such as fertility control or treatment of steroid-dependent diseases.

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“…Equine testis evaluation 12 h after dexamethasone administration show a decrease in the expression of genes involved in steroidogenesis and in GR signalling (Ing et al, 2014). Two genes related to male fertility (heat shock protein DNAJC4 and sperm‐specific calcium channel CATSPER1 mRNAs) were more than 60% depressed 15 days after punctual dexamethasone administration (Ing et al, 2015). Histological assessment of feline testis after prednisolone treatment for 50 days shows impaired sperm quality and testicular function illustrated with higher Sertoli cells apoptosis and abnormal sperm (Andrews et al, 2022).…”

Section: The Role Of the Hpa System On The Hpgmentioning

confidence: 99%

Pathogenesis of the crosstalk between reproductive function and stress in animals—part 1: Hypothalamo–pituitary–adrenal axis, sympatho‐adrenomedullary system and kisspeptin

Kaiser,

Jaillardon

2023

Reprod Domestic Animals

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Stress is defined as a disruption of the body homeostasis in response to modest as well as perceived challenge. Two main physiological routes, the hypothalamic–pituitary–adrenal system (HPA) and the sympatho‐adrenomedullary system (SAM), aim to maintain or restore homeostasis by mutual interaction. SAM is quickly‐reacting as it primarily works through the nervous system—the sympathetic nervous system. In response to stress, signals are sent to activate the adrenal medulla which releases catecholamines (primarily adrenaline and norepinephrine). The catecholamines have a momentary effect on the body's organs that are prepared for a fight situation. At the same time, the stressor activates the HPA axis by signals from the brain causing secretion of the pituitary hormone adrenocorticotropic hormone (ACTH). ACTH acts on the adrenal cortex, which secretes glucocorticoids, including cortisol. Since HPA primarily works through hormones, the system is slightly slower than SAM and gives rise to a metabolic effect. While short‐term stress response is an adaptive and beneficial process, chronic or excessive stress can lead to a range of negative health outcomes including reproductive disorders and infertility. Several mechanisms have been proposed to explain the link between stress and reproduction. This includes in particular kisspeptin, which is closely related to reproduction, as it is a powerful stimulator of the Hypothalamic–pituitary–gonadal (HPG) system. The present review, through current knowledge in various male and female species, deals with the role of the SAM and the HPA, including the major action of kisspeptin and glucocorticoids that trigger the consequences of psychological or physiological stress on reproductive function.

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Dexamethasone acutely regulates endocrine parameters in stallions and subsequently affects gene expression in testicular germ cells

Cited by 10 publications

References 32 publications

Grape seed extract attenuates dexamethasone‐induced testicular and thyroid dysfunction in male albino rats

Grape seed extract attenuates dexamethasone‐induced testicular and thyroid dysfunction in male albino rats

Conservation of glutathione S-transferase mRNA and protein sequences similar to human and horse Alpha class GST A3-3 across dog, goat, and opossum species

Pathogenesis of the crosstalk between reproductive function and stress in animals—part 1: Hypothalamo–pituitary–adrenal axis, sympatho‐adrenomedullary system and kisspeptin

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