Corticosterone biosynthesis in mouse clonal myoblastic C2C12 cells

Fujiki, Jumpei; Maeda, Naoyuki; Sato, M.; Ieko, Takahiro; Inoue, Hiroki; Iwasaki, Tomohito; Iwano, Hidetomo; Yokota, Hiroshi

doi:10.1016/j.steroids.2018.07.001

Cited by 8 publications

(5 citation statements)

References 52 publications

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“…Dehydroepiandrosterone (DHEA)-sulfate is produced in the adrenal cortex and transported via the blood to peripheral tissues such as the placenta, where it is de-conjugated to form DHEA and serves as the substrate for TS and estrogen production (36, 37). We initially reported that PGN-S is the primary substrate for steroidogenesis in mouse clonal myoblastic C2C12 cells (27). Because PGN-S is abundant in rat blood (33), we postulated that PGN-S serves as the primary substrate for steroidogenesis in SGs as well.…”

Section: Discussionmentioning

confidence: 99%

“…Expression of enzymes involved in steroidogenesis has also been detected in human vascular cells and the heart, suggesting local steroid synthesis in the cardiovascular system (24, 25). In addition to these examples, CORT is also reportedly synthesized in the testis and mouse clonal myoblastic C2C12 cells (26, 27). Although numerous reports describe local steroid synthesis in a variety of organs, local steroid synthesis in the salivary gland has not been reported to date.…”

Section: Introductionmentioning

confidence: 95%

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Analysis of Corticosterone and Testosterone Synthesis in Rat Salivary Gland Homogenates

et al. 2019

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Extra-adrenal steroid hormone production has been reported in several tissues, the biological role of which is interesting in terms of hormonal regulation of metabolism, growth, and behavior. In this report, we describe for the first time steroidogenesis in rat salivary glands. Enzyme activities associated with corticosterone and testosterone production were detected in rat salivary glands by LC-MS analysis. In tissue homogenates of rat salivary glands, progesterone was produced enzymatically in vitro from pregnenolone in the presence of NADPH and NADH. Deoxycorticosterone was produced from progesterone, corticosterone from deoxycorticosterone, and testosterone from androstenedione (but not pregnenolone from cholesterol) via enzymatic reactions using the same tissue homogenates. Immunoblotting analysis indicated the expression of 11β-hydroxylase (cytochrome P450 11β1; CYP11β1), which mediated the production of corticosterone from deoxycorticosterone. However, CYP family 11 subfamily A member 1 (CYP11A1)-mediated production of pregnenolone from cholesterol was not detected in the salivary glands by immunoblotting using a specific antibody. These results indicate that corticosterone and testosterone are produced from pregnenolone in rat salivary glands. The initial substrate in salivary steroidogenesis and the roles of salivary corticosterone and testosterone are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Analysis of Corticosterone and Testosterone Synthesis in Rat Salivary Gland Homogenates

et al. 2019

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“…In particular, 17β-hydroxysteroid (17β-HSD), 3β-hydroxysteroid (3β-HSD), 5α-reductase, and P450 aromatase are particularly expressed in the ovary, in testis, and in the brain, but also in muscles, such as the gastrocnemius, which presents the highest expression of 3 β-HSD, and the soleus, with the highest expression of P450 aromatase [ 42 ]. Although studies conducted on C2C12 revealed the enzymatic activity of 3β-HSD, the presence of the protein was still not detected in their results [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Peroxide Stimulates Dihydrotestosterone Release in C2C12 Myotubes: A New Perspective for Exercise-Related Muscle Steroidogenesis?

Antinozzi

Duranti

Ceci

et al. 2022

IJMS

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Skeletal muscle is a tissue that has recently been recognized for its ability to produce androgens under physiological conditions. The steroidogenesis process is known to be negatively influenced by reactive oxygen species (ROS) in reproductive Leydig and ovary cells, while their effect on muscle steroidogenesis is still an unexplored field. Muscle cells are continuously exposed to ROS, resulting from both their metabolic activity and the surrounding environment. Interestingly, the regulation of signaling pathways, induced by mild ROS levels, plays an important role in muscle fiber adaptation to exercise, in a process that also elicits a significant modulation in the hormonal response. The aim of the present study was to investigate whether ROS could influence steroidogenesis in skeletal muscle cells by evaluating the release of testosterone (T) and dihydrotestosterone (DHT), as well as the evaluation of the relative expression of the key steroidogenic enzymes 5α-reductase, 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, and aromatase. C2C12 mouse myotubes were exposed to a non-cytotoxic concentration of hydrogen peroxide (H2O2), a condition intended to reproduce, in vitro, one of the main stimuli linked to the process of homeostasis and adaptation induced by exercise in skeletal muscle. Moreover, the influence of tadalafil (TAD), a phosphodiesterase 5 inhibitor (PDE5i) originally used to treat erectile dysfunction but often misused among athletes as a “performance-enhancing” drug, was evaluated in a single treatment or in combination with H2O2. Our data showed that a mild hydrogen peroxide exposure induced the release of DHT, but not T, and modulated the expression of the enzymes involved in steroidogenesis, while TAD treatment significantly reduced the H2O2-induced DHT release. This study adds a new piece of information about the adaptive skeletal muscle cell response to an oxidative environment, revealing that hydrogen peroxide plays an important role in activating muscle steroidogenesis.

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“…As such, and based on previous reports [75,76], the 10% FBS-supplemented medium was replaced with FBS-free medium in the current study. Furthermore, both medium [77][78][79][80][81][82][83] and cells [84] have previously been used as samples. Following analysis, it was observed that testosterone, androsterone, progesterone, and estrone levels were significantly decreased in the NPC model cells (Figure 4 and Table S6).…”

Section: Steroid Hormone Analysis In Npc Model Cellmentioning

confidence: 99%

Metabolic Alteration Analysis of Steroid Hormones in Niemann–Pick Disease Type C Model Cell Using Liquid Chromatography/Tandem Mass Spectrometry

Abe

Maekawa

Sato

et al. 2022

IJMS

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Niemann–Pick disease type C (NPC) is an autosomal recessive disease caused by a functional deficiency of cholesterol-transporting proteins in lysosomes, and exhibits various clinical symptoms. Since mitochondrial dysfunction in NPC has recently been reported, cholesterol catabolism to steroid hormones may consequently be impaired. In this study, we developed a comprehensive steroid hormone analysis method using liquid chromatography/tandem mass spectrometry (LC–MS/MS) and applied it to analyze changes in steroid hormone concentrations in NPC model cells. We investigated the analytical conditions for simultaneous LC–MS/MS analysis, which could be readily separated from each other and showed good reproducibility. The NPC phenotype was verified as an NPC model with mitochondrial abnormalities using filipin staining and organelle morphology observations. Steroid hormones in the cell suspension and cell culture medium were also analyzed. Steroid hormone analysis indicated that the levels of six steroid hormones were significantly decreased in the NPC model cell and culture medium compared to those in the wild-type cell and culture medium. These results indicate that some steroid hormones change during NPC pathophysiology and this change is accompanied by mitochondrial abnormalities.

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Corticosterone biosynthesis in mouse clonal myoblastic C2C12 cells

Cited by 8 publications

References 52 publications

Analysis of Corticosterone and Testosterone Synthesis in Rat Salivary Gland Homogenates

Analysis of Corticosterone and Testosterone Synthesis in Rat Salivary Gland Homogenates

Hydrogen Peroxide Stimulates Dihydrotestosterone Release in C2C12 Myotubes: A New Perspective for Exercise-Related Muscle Steroidogenesis?

Metabolic Alteration Analysis of Steroid Hormones in Niemann–Pick Disease Type C Model Cell Using Liquid Chromatography/Tandem Mass Spectrometry

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