Gonadotropin-releasing hormone positively regulates steroidogenesis via extracellular signal-regulated kinase in rat Leydig cells

Yao, Bing; Liu, Haiyan; Gu, Yan; Shi, Suozhu; Tao, Xiao-qian; Li, Xiaojun; Ge, Yong; Cui, Ying‐Xia; Yang, Guobin

doi:10.1038/aja.2010.158

Cited by 22 publications

(12 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 29 Our previous study demonstrated that the synthesis of annexin A5 is stimulated by GnRH and hCG, and GnRH positively regulates steroidogenesis by activating ERK in rat Leydig cells. 18 30 ERK1/2 but not JNKs or p38-MAPKs was activated by GnRH in our previous study, 30 and ERK1/2 is also activated by annexin A5 in the current study. Interestingly, JNKs or p38-MAPKs were not activated by annexin A5 in our study.…”

Section: Discussionsupporting

confidence: 62%

Annexin A5 regulates Leydig cell testosterone production via ERK1/2 pathway

Sun

Liang

et al. 2016

Asian J Androl

Self Cite

View full text Add to dashboard Cite

This study was to investigate the effect of annexin A5 on testosterone secretion from primary rat Leydig cells and the underlying mechanisms. Isolated rat Leydig cells were treated with annexin A5. Testosterone production was detected by chemiluminescence assay. The protein and mRNA of Steroidogenic acute regulatory (StAR), P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), and 17α-hydroxylase were examined by Western blotting and semi-quantitative RT-PCR, respectively. Annexin A5 significantly stimulated testosterone secretion from rat Leydig cells in dose- and time-dependent manners and increased mRNA and protein expression of StAR, P450scc, 3β-HSD, and 17β-HSD but not 17α-hydroxylase. Annexin A5 knockdown by siRNA significantly decreased the level of testosterone and protein expression of P450scc, 3β-HSD, and 17β-HSD. The significant activation of ERK1/2 signaling was observed at 5, 10, and 30 min after annexin A5 treatment. After the pretreatment of Leydig cells with ERK inhibitor PD98059 (50 μmol l−1) for 20 min, the effects of annexin A5 on promoting testosterone secretion and increasing the expression of P450scc, 3β-HSD, and 17β-HSD were completely abrogated (P < 0.05). Thus, ERK1/2 signaling is involved in the roles of annexin A5 in mediating testosterone production and the expression of P450scc, 3β-HSD, and 17β-HSD in Leydig cells.

show abstract

Section: Discussionsupporting

confidence: 62%

Annexin A5 regulates Leydig cell testosterone production via ERK1/2 pathway

Sun

Liang

et al. 2016

Asian J Androl

Self Cite

View full text Add to dashboard Cite

show abstract

“…Testicular GnRH receptors have been reported in several species, including humans (87,88). In rats, GnRH affects Ca 2+ mobilisation (89) as well as steroidogenesis in Leydig cells (90). This reported direct effect of GnRH on steroidogenesis is especially noteworthy for the present study because, although testosterone implants returned testosterone concentrations to the normal range in castrated rats, the elevation in testosterone was lower in deslorelin‐treated intact rats.…”

Section: Discussionmentioning

confidence: 99%

Predominant Suppression of Follicle‐Stimulating Hormone β‐Immunoreactivity after Long‐Term Treatment of Intact and Castrate Adult Male Rats with the Gonadotrophin‐Releasing Hormone Agonist Deslorelin

Smith

Cheryl

Edwards

et al. 2012

J Neuroendocrinology

View full text Add to dashboard Cite

GnRH agonists are used to treat gonadal steroid-dependent disorders in humans and contracept animals. These agonists are thought to work by desensitizing gonadotropes to GnRH, thereby suppressing FSH and LH secretion. It is not known whether changes occur in the cellular composition of the pituitary gland following chronic GnRH agonist exposure. Adult male Sprague-Dawley rats were treated with a sham, deslorelin, or deslorelin plus testosterone implant for 41.0±0.6 days. In a second experiment, rats were castrated and treated with deslorelin and/or testosterone. Pituitary sections were labeled immunocytochemically for FSHβ and LHβ, or αGSU. Deslorelin suppressed testis weight by two thirds and reduced plasma FSH and LH in intact rats. Deslorelin decreased the percentage of gonadotropes but the effect was specific to the FSHβ-ir cells. Testosterone did not reverse the deslorelin-induced reduction in the overall gonadotrope population. However, in the presence of testosterone, the proportion of gonadotropes that was FSHβ-ir increased in the remaining gonadotropes. There was no effect of treatment on the total LHβ-ir cell population although the loss of FSHβ in bi-hormonal cells increased the proportion of mono-hormonal LHβ-ir gonadotropes. The castration-induced plasma LH and FSH increases were suppressed by deslorelin, testosterone or both. Castration increased both LH-ir and FSH-ir without increasing the overall gonadotrope population; thus increasing the proportion of bi-hormonal cells. Deslorelin suppressed these increases. Testosterone increased FSH-ir in deslorelin-treated castrate rats. Deslorelin did not affect αGSU immunoreactivity, suggesting that the gonadotrope population per se is not eliminated by deslorelin but the ability of gonadotropes to synthesize FSHβ is compromised. We hypothesize that the FSH dominant suppression may be central to the long-term contraceptive efficacy of deslorelin in the male.

show abstract

“…Annexin V and 3-β-hydroxysteroid dehydrogenase (HSD) were also shown to colocalize in the Leydig cells16. Our previous studies showed that GnRH agonist increased the mRNA and protein levels of annexin V in primary rat Leydig cells in vitro 17, as well as the secretion of testosterone18, annexin V could increase testosterone production and promote cell proliferation of Leydig cells. During the puberty, the proliferation of Leydig cell precursors is required to increase the number of Leydig cells.…”

mentioning

confidence: 96%

Annexin V-induced rat Leydig cell proliferation involves Ect2 via RhoA/ROCK signaling pathway

Jing

Chen

et al. 2015

Sci Rep

Self Cite

View full text Add to dashboard Cite

This study investigated the effect of annexin V on the proliferation of primary rat Leydig cells and the potential mechanism. Our results showed that annexin V promoted rat Leydig cell proliferation and cell cycle progression in a dose- and time-dependent manner. Increased level of annexin V also enhanced Ect2 protein expression. However, siRNA knockdown of Ect2 attenuated annexin V-induced proliferation of rat Leydig cells. Taken together, these data suggest that increased level of annexin V induced rat Leydig cell proliferation and cell cycle progression via Ect2. Since RhoA activity was increased following Ect2 activation, we further investigated whether Ect2 was involved in annexin V-induced proliferation via the RhoA/ROCK pathway, and the results showed that annexin V increased RhoA activity too, and this effect was abolished by the knockdown of Ect2. Moreover, inhibition of the RhoA/ROCK pathway by a ROCK inhibitor, Y27632, also attenuated annexin V-induced proliferation and cell cycle progression. We thus conclude that Ect2 is involved in annexin V-induced rat Leydig cell proliferation through the RhoA/ROCK pathway.

show abstract

Gonadotropin-releasing hormone positively regulates steroidogenesis via extracellular signal-regulated kinase in rat Leydig cells

Cited by 22 publications

References 39 publications

Annexin A5 regulates Leydig cell testosterone production via ERK1/2 pathway

Annexin A5 regulates Leydig cell testosterone production via ERK1/2 pathway

Predominant Suppression of Follicle‐Stimulating Hormone β‐Immunoreactivity after Long‐Term Treatment of Intact and Castrate Adult Male Rats with the Gonadotrophin‐Releasing Hormone Agonist Deslorelin

Annexin V-induced rat Leydig cell proliferation involves Ect2 via RhoA/ROCK signaling pathway

Contact Info

Product

Resources

About