Luteinizing hormone-induced Akt phosphorylation and androgen production are modulated by MAP Kinase in bovine theca cells

Fukuda, Shin; Orisaka, Makoto; Tajima, Kimihisa; Hattori, Katsushige; Kotsuji, Fumikazu

doi:10.1186/1757-2215-2-17

Cited by 68 publications

(50 citation statements)

References 37 publications

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“…This hypothesis is confirmed by the recent finding that the capacity of luteinized granulosal cells isolated from dominant follicles and of luteal cells isolated from CL on day 12 of the estrous cycle to produce progesterone basally and in response to LH are lower for cattle with low versus high AFC ). Moreover, two recent studies showed that LH significantly increased androstenedione production in bovine thecal cells (in accordance with our results), and that addition of two inhibitors of the phosphatidylinositol-3-kinase/Akt signaling pathway significantly decreased LH-induced androstenedione production (Fukuda et al 2009), inhibition of the Akt and Erk pathway inhibited both basal and LH-induced androstenedione secretion by animals) versus high (solid symbols, nZ4) AFC. Animals were synchronized with two injections of PG administered 11 days apart, and blood samples were collected daily from day 6 to 21 of the estrous cycle.…”

Section: Discussionsupporting

confidence: 78%

“…Recent evidence shows that LH significantly increases CYP17A1 mRNA expression in thecal cells (Fukuda et al 2009), and in this study, it was shown that CYP17A1 mRNA expression was higher in thecal cells from cattle with a high AFC, despite lower basal and episodic LH secretion ). Therefore, the reduced androgen production in animals with a low AFC could be due to an alteration in LH signaling which, in turn, may alter CYP17A1 mRNA expression.…”

Section: Discussionmentioning

confidence: 74%

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Evidence that high variation in antral follicle count during follicular waves is linked to alterations in ovarian androgen production in cattle

Mossa¹,

Jimenez-Krassel²,

Folger³

et al. 2010

Reproduction

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Androgens have an important role in ovarian follicular growth and function, but circulating androgen concentrations are also associated with ovarian dysfunction, cardiovascular disease, and metabolic disorders in women. The extent and causes of the variation in androgen production in individuals, however, are unknown. Because thecal cells of follicles synthesize androstenedione and testosterone, variation in production of these androgens is hypothesized to be directly related to the inherently high variation in number of healthy growing follicles in ovaries of individuals. To test this hypothesis, we determined whether thecal CYP17A1 mRNA (codes for a cytochrome P450 enzyme involved in androgen synthesis), LH-induced thecal androstenedione production, androstenedione concentrations in follicular fluid, and circulating testosterone concentrations were lower in cattle with relatively low versus high number of follicles growing during follicular waves and whether ovariectomy reduced serum testosterone concentrations. Results demonstrated that cattle with a low follicle number had lower (P!0.05) abundance of CYP17A1 mRNA in thecal cells, reduced (P!0.01) capacity of thecal cells to produce androstenedione in response to LH, lower (P!0.01) androstenedione concentrations in ovulatory follicles, and lower (P!0.02) circulating testosterone concentrations during estrous cycles compared with animals with high follicle number. Also, serum testosterone in cattle with low or high follicle number was reduced by 63 and 70%, respectively, following ovariectomy. In conclusion, circulating androgen concentrations are lower in cattle with low versus high number of follicles growing during follicular waves, possibly because of a reduced responsiveness of thecal cells to LH.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 74%

Evidence that high variation in antral follicle count during follicular waves is linked to alterations in ovarian androgen production in cattle

Mossa¹,

Jimenez-Krassel²,

Folger³

et al. 2010

Reproduction

View full text Add to dashboard Cite

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“…Previously, these pathways have been shown to be involved in the regulation of ovarian functions such as gene expression of key steroidogenic genes [33,34]. Furthermore, cross talk between the Akt/PKB and Erk1/2 pathways had been previously described in several cell types [35].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol potentiates effects of simvastatin on inhibition of rat ovarian theca-interstitial cells steroidogenesis

et al. 2014

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BackgroundPolycystic ovary syndrome (PCOS) is characterized by ovarian enlargement, hyperplastic theca compartment and increased androgen production due to, at least in part, excessive expression of several key genes involved in steroidogenesis. Previously, our group has demonstrated that simvastatin, competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), a rate-limiting step of the mevalonate pathway, reduces rat-theca interstitial cell steroidogenesis by inhibiting Cyp17a1 gene expression, the key enzyme of the androgen biosynthesis pathway. Recently, we demonstrated that resveratrol, a bioflavonoid abundant in red grapes, decreases rat theca-interstitial cell steroidogenesis and this suppressive effect is mediated through mechanisms independent of the mevalonate pathway. The present study evaluated the effect of combining simvastatin and resveratrol treatments on rat theca-interstitial cell steroidogenesis.MethodsRat theca-interstitial cells isolated from 30 day-old female rats were cultured for up to 48 h with or without simvastatin (1 μM) and/or resveratrol (3-10 μM). Steroidogenic enzymes gene expression was evaluated by quantitative real time PCR and steroid levels were measured by liquid chromatography-mass spectrometry. Comparisons between groups were performed using ANOVA and Tukey test.ResultsResveratrol potentiated inhibitory effects of simvastatin on androstenedione and androsterone production in theca-interstitial cells. This suppressive effect correlated with profound inhibition in Cyp17a1 mRNA expression in the presence of a combination of resveratrol and simvastatin.ConclusionsThe present findings indicate that resveratrol potentiates the simvastatin-induced inhibitory effect on theca-interstitial cell androgen production, raising the possibility of development of novel treatments of PCOS.

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“…AKT (Fig. 2) becomes phosphorylated in the follicular cells in rat and bovine species following LH treatment (Carvalho et al 2003, Fukuda et al 2009). …”

Section: Cell Signalingmentioning

confidence: 99%

Cumulus cell gene expression following the LH surge in bovine preovulatory follicles: potential early markers of oocyte competence

Assidi¹,

Dieleman²,

Sirard³

2010

Reproduction

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Cumulus cells (CCs) are essential for oocytes to reach full development competency and become fertilized. Many major functional properties of CCs are triggered by gonadotropins and governed by the oocyte. Consequently, cumulus may reflect oocyte quality and is often used for oocyte selection. The most visible function of CCs is their ability for rapid extracellular matrix expansion after the LH surge. Although unexplained, LH induces the final maturation and improves oocyte quality. To study the LH signaling and gene expression cascade patterns close to the germinal vesicle breakdown, bovine CCs collected at 2 h before and 6 h after the LH surge were hybridized to a custom-made microarray to better understand the LH genomic action and find differentially expressed genes associated with the LH-induced oocyte final maturation. Functional genomic analysis of the 141 overexpressed and 161 underexpressed clones was performed according to their molecular functions, gene networks, and cell compartments. Following real-time PCR validation of our gene lists, some interesting pathways associated with the LH genomic action on CCs and their possible roles in oocyte final maturation, ovulation, and fertilization are discussed. A list of early potential markers of oocyte competency in vivo and in vitro is thereafter suggested. These early biomarkers are a preamble to understand the LH molecular pathways that trigger the final oocyte competence acquisition process in bovine.

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Luteinizing hormone-induced Akt phosphorylation and androgen production are modulated by MAP Kinase in bovine theca cells

Cited by 68 publications

References 37 publications

Evidence that high variation in antral follicle count during follicular waves is linked to alterations in ovarian androgen production in cattle

Evidence that high variation in antral follicle count during follicular waves is linked to alterations in ovarian androgen production in cattle

Resveratrol potentiates effects of simvastatin on inhibition of rat ovarian theca-interstitial cells steroidogenesis

Cumulus cell gene expression following the LH surge in bovine preovulatory follicles: potential early markers of oocyte competence

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