Regulation of Leydig cells through a steroidogenic acute regulatory protein-independent pathway by a lipophilic factor from macrophages

Lukyanenko, YO; Am, Carpenter; Brigham, DE; Stocco, DM; Hutson, JC

doi:10.1677/joe.0.1580267

Cited by 32 publications

(21 citation statements)

References 36 publications

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“…However, our results indicated that cordycepin could not induce StAR protein and StAR promoter expressions in MA-10 cells. Our data are somewhat inconsistent to several studies that steroidogenesis could be trigger by cAMP and StAR-independent pathways [57–59]. Therefore, it is possible that the cordycepin could possibly acitvate MAPK-ERK 1/2 and PKC pathways without increasing of StAR promoter and StAR protein expression to induce steroidogenesis in MA-10 cells, which will be worth to further investigate.…”

Section: Discussioncontrasting

confidence: 93%

The Effect of Cordycepin on Steroidogenesis and Apoptosis in MA‐10Mouse Leydig Tumor Cells

Pan

Lin

Huang

2011

Evidence-Based Complementary and Alternative Medicine

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Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS). We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR) subtype agonists were further used to treat MA-10 cells, showing that A1, A 2A , A 2B , and A3, AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

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Section: Discussioncontrasting

confidence: 93%

The Effect of Cordycepin on Steroidogenesis and Apoptosis in MA‐10Mouse Leydig Tumor Cells

Pan

Lin

Huang

2011

Evidence-Based Complementary and Alternative Medicine

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“…This macrophage-Leydig interdigitation has been documented as early as 20-30 days postnatally in rats, just prior to pubertal testosterone secretion (Christensen and Gillim 1969;Hutson 1992;Miller et al 1983). Their close proximity and cellular interdigitation has been thought to modulate the production of testosterone through lipophilic factors and/or cytokines (Hales 2002;Hutson 1998;Lukyanenko et al 1998;Watson et al 1994). Some cytokines (including interleukin-1, tumor necrosis factor-α, interleukin-6, transforming growth factor-β (TGFβ), interferon-γ, lipopolysaccharide, reactive oxygen species, and nitric oxide) are known to decrease steroidogenesis (reviewed by Hales 2002), whereas unidentified lipophilic factors seem to increase testosterone production (Hutson 1998).…”

Section: Cells Of the Interstitiummentioning

confidence: 98%

Origin and Differentiation of Androgen-Producing Cells in the Gonads

Potter

Kumar

DeFalco

2016

Results and Problems in Cell Differentiation

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Sexual reproduction is dependent on the activity of androgenic steroid hormones to promote gonadal development and gametogenesis. Leydig cells of the testis and theca cells of the ovary are critical cell types in the gonadal interstitium that carry out steroidogenesis and provide key androgens for reproductive organ function. In this chapter, we will discuss important aspects of interstitial androgenic cell development in the gonad, including: the potential cellular origins of interstitial steroidogenic cells and their progenitors; the molecular mechanisms involved in Leydig cell specification and differentiation (including Sertoli-cell-derived signaling pathways and Leydig-cell-related transcription factors and nuclear receptors); the interactions of Leydig cells with other cell types in the adult testis, such as Sertoli cells, germ cells, peritubular myoid cells, macrophages, and vascular endothelial cells; the process of steroidogenesis and its systemic regulation; and a brief discussion of the development of theca cells in the ovary relative to Leydig cells in the testis. Finally, we will describe the dynamics of steroidogenic cells in seasonal breeders and highlight unique aspects of steroidogenesis in diverse vertebrate species. Understanding the cellular origins of interstitial steroidogenic cells and the pathways directing their specification and differentiation has implications for the study of multiple aspects of development and will help us gain insights into the etiology of reproductive system birth defects and infertility.

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“…A number of studies have also focussed on deciphering the mechanism involved in macrophage regulation of Leydig cell function. Using macrophage‐conditioned media a lipophilic factor has been identified (Hutson et al ., 1996) which appears to alter Leydig cell androgen synthesis through a StAR‐independent pathway (Lukyanenko et al ., 1998). …”

Section: Macrophagesmentioning

confidence: 99%

Cell‐specific ablation in the testis: what have we learned?

2015

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SummaryTesticular development and function is the culmination of a complex process of autocrine, paracrine and endocrine interactions between multiple cell types. Dissecting this has classically involved the use of systemic treatments to perturb endocrine function, or more recently, transgenic models to knockout individual genes. However, targeting genes one at a time does not capture the more wide‐ranging role of each cell type in its entirety. An often overlooked, but extremely powerful approach to elucidate cellular function is the use of cell ablation strategies, specifically removing one cellular population and examining the resultant impacts on development and function. Cell ablation studies reveal a more holistic overview of cell–cell interactions. This not only identifies important roles for the ablated cell type, which warrant further downstream study, but also, and importantly, reveals functions within the tissue that occur completely independently of the ablated cell type. To date, cell ablation studies in the testis have specifically removed germ cells, Leydig cells, macrophages and recently Sertoli cells. These studies have provided great leaps in understanding not possible via other approaches; as such, cell ablation represents an essential component in the researchers’ tool‐kit, and should be viewed as a complement to the more mainstream approaches to advancing our understanding of testis biology. In this review, we summarise the cell ablation models used in the testis, and discuss what each of these have taught us about testis development and function.

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Regulation of Leydig cells through a steroidogenic acute regulatory protein-independent pathway by a lipophilic factor from macrophages

Cited by 32 publications

References 36 publications

The Effect of Cordycepin on Steroidogenesis and Apoptosis in MA‐10Mouse Leydig Tumor Cells

The Effect of Cordycepin on Steroidogenesis and Apoptosis in MA‐10Mouse Leydig Tumor Cells

Origin and Differentiation of Androgen-Producing Cells in the Gonads

Cell‐specific ablation in the testis: what have we learned?

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