Protective effects of estrogens and caloric restriction during aging on various rat testis parameters

Hamden, Khaled; Silandre, Dorothèe; Delalande, Christelle; Elfeki, Abdelfattah; Carreau, Serge

doi:10.1111/j.1745-7262.2008.00430.x

Cited by 39 publications

(34 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…17beta-estradiol was shown to have protective roles in aged testes by increasing superoxide dismutase activity and decreasing the activity of testicular enzymes. 22 Blockade of estrogen receptor (with the estrogen receptor antagonist, ICI 182780) was used in this study. On the other hand, we found the approximately 20 and 40% reduction in cell viability in testosterone deprivation TM3 culture and in human ovarian granulosa cells treated with 40-nmol l 21 testosterone (unpublished data), respectively, showing that the protective effects of lowdose testosterone are specific to Leydig cells.…”

Section: Discussionmentioning

confidence: 99%

Low-dose testosterone treatment decreases oxidative damage in TM3 Leydig cells

Hwang¹,

Liao²,

Lin³

et al. 2011

Asian J Androl

View full text Add to dashboard Cite

Testosterone replacement therapy has benefits for aging men and those with hypogonadism. However, the effects of exogenous testosterone on Leydig cells are still unclear and need to be clarified. In this report, we demonstrate that testosterone supplementation can reduce oxidative damage in Leydig cells. The TM3 Leydig cell line was used as an in vitro cell model in this study. Cytoprotective effects were identified with 100-nmol l 21 testosterone treatment, but cytotoxic effects were found with o500-nmol l 21 testosterone supplementation. Significantly reduced reactive oxygen species (ROS) generation, lipid peroxide contents and hypoxia induction factor (HIF)-1a stabilization and activation were found with 100-nmol l 21 testosterone treatment. There was a 1.72-fold increase in ROS generation in the 500-nmol l 21 compared to the 100-nmol l 21 testosterone treatment. A 1.58-fold increase in steroidogenic acute regulatory protein (StAR) expression was found in 50-nmol l 21 testosterone-treated cells (P,0.01). Chemically induced hypoxia was attenuated by testosterone supplementation. Leydig cells treated with low-dose testosterone supplementation showed cytoprotection by decreasing ROS and lipid peroxides, increasing StAR expression and relieving hypoxia stress as demonstrated by HIF-1a stabilization. Increased oxidative damage was found with o500-nmol l 21 testosterone manipulation. The mechanism governing the differential dose effects of testosterone on Leydig cells needs further investigation in order to shed light on testosterone replacement therapy. INTRODUCTIONTestosterone plays an important role in normal growth and development of male sex organs. It is also known to be a key player in glucose homeostasis and lipid metabolism. 1 More recently, gonadotrophinreleasing hormones I and II were demonstrated to stimulate testosterone production in murine Leydig cells. 2 In the testes, Leydig cells synthesize and secrete testosterone in response to luteinizing hormone, which is counter-regulated by feedback influences of testosterone and its metabolites. Testosterone levels notably decline with aging; 3,4 however, a recent report showed no correlation between androgen receptor (AR) polymorphism and the serum concentrations of total and free testosterone in elderly men. 5 The mechanism by which aged Leydig cells lose their steroidogenic function remains unclear. It was proposed that decreases in testosterone levels with aging may reflect reactive oxygen species (ROS) elevation and further disruption of the ability of Leydig cells to produce testosterone. 6,7 Mitochondrial respiration, which typically consumes about 90% of the oxygen utilized by cells, is considered to be the major source of cellular ROS. 8 ROS cause tissue damage by a variety of mechanisms including DNA damage, lipid peroxidation, protein oxidation and carbonylation, depletion of cellular thiols and activation of proinflammatory cytokine release. Mitochondrial-derived ROS were implicated in a number of disease and disorders, including neurodegenerat...

show abstract

Section: Discussionmentioning

confidence: 99%

Low-dose testosterone treatment decreases oxidative damage in TM3 Leydig cells

Hwang¹,

Liao²,

Lin³

et al. 2011

Asian J Androl

View full text Add to dashboard Cite

show abstract

“…Results of studies have revealed a correlation between decreasing E 2 levels in the testis and decreasing sperm production during ageing and indicated that E 2 can attenuate the age-related decline in spermatogenesis (Hamden et al 2008, Clarke & Pearl 2014. On the other hand, overexposure to E 2 , synthetic estrogens, like DES, and SERMs, like tamoxifen and BPA, cause deleterious effects on the male reproductive tract and fertility.…”

Section: Discussionmentioning

confidence: 99%

Effect of estrogen receptor-subtype-specific ligands on fertility in adult male rats

Dumasia

Kumar

Kadam

et al. 2015

Journal of Endocrinology

View full text Add to dashboard Cite

Maintenance of normal male fertility relies on the process of spermatogenesis which is under complex endocrine control by mechanisms involving gonadotropin and steroid hormones. Although testosterone is the primary sex steroid in males, estrogen is locally produced in the testis and plays a very crucial role in male fertility. This is evident from presence of both the estrogen receptors alpha (ERa) and beta (ERb) in the testis and their absence, as in the case of knockout mice models, leads to sterility. The present study was undertaken to understand individual roles of the two ERs in spermatogenesis and their direct contribution towards the maintenance of male fertility using receptor-subtype-specific ligands. Administration of ERa and b agonists to adult male rats for 60 days results in a significant decrease in fertility, mainly due to an increase in pre-and post-implantation loss and a concomitant decrease in litter size and sperm counts. Our results indicate that ERa is mainly involved in negative feedback regulation of gonadotropin hormones, whereas both ERs are involved in regulation of prolactin and testosterone production. Histological examinations of the testis reveal that ERb could be involved in the process of spermiation since many failed spermatids were observed in stages IX-XI following ERb agonist treatment. Our results indicate that overactivation of estrogen signaling through either of its receptors can have detrimental effects on the fertility parameters and that the two ERs have both overlapping and distinct roles in maintenance of male fertility.

show abstract

“…In addition, recent studies have shown that flavonoids (antioxidants, such as genistein, myricetin, and quercetin) can protect the intestinal TJ barrier function from oxidative stress-induced barrier disruption caused by inflammatory cytokines, enteric bacteria, and chemicals (e.g., acetaldehyde) (Suzuki and Hara, 2011), illustrating the damaging effects of oxidative stress on TJ barrier function. In this context, it is of interest to note that estrogens (or phytoestrogens) act as scavengers of free radicals, protecting the testis and the liver from oxidative stress-induced injury (Hamden et al, 2008(Hamden et al, , 2009). Thus, the protective role of estrogens in environmental toxicant-induced oxidative stress that leads to testicular injury must be carefully evaluated.…”

Section: Cellular Targets Of Cadmium In the Testismentioning

confidence: 99%