Age-dependent stimulation of Leydig cell steroidogenesis by interleukin-1 isoforms

Svechnikov, Konstantin; Sultana, Taranum; Söder, Olle

doi:10.1016/s0303-7207(01)00554-8

Cited by 87 publications

(60 citation statements)

References 42 publications

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“…20 Briefly, the testes were isolated and decapsulated. They were then incubated with collagenase type I (0.25 mg ml 21 ) for 20 min at 37 uC.…”

Section: Isolation and Culturing Of Leydig Cellsmentioning

confidence: 99%

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

Yao

Liu²,

Gu³

et al. 2011

Asian J Androl

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Gonadotropin-releasing hormone (GnRH) is secreted from neurons within the hypothalamus and is necessary for reproductive function in all vertebrates. GnRH is also found in organs outside of the brain and plays an important role in Leydig cell steroidogenesis in the testis. However, the signalling pathways mediating this function remain largely unknown. In this study, we investigated whether components of the mitogen-activated protein kinase (MAPK) pathways are involved in GnRH agonist (GnRHa)-induced testis steroidogenesis in rat Leydig cells. Primary cultures of rat Leydig cells were established. The expression of 3b-hydroxysteroid dehydrogenase (3b-HSD) and the production of testosterone in response to GnRHa were examined at different doses and for different durations by RT-PCR, Western blot analysis and radioimmunoassay (RIA). The effects of GnRHa on ERK1/2, JNK and p38 kinase activation were also investigated in the presence or absence of the MAPK inhibitor PD-98059 by Western blot analysis. GnRHa induced testosterone production and upregulated 3b-HSD expression at both the mRNA and protein levels; it also activated ERK1/2, but not JNK and p38 kinase. Although the maximum effects of GnRHa were observed at a concentration of 100 nmnol L 21 after 24 h, activation of ERK1/2 by GnRHa reached peak at 5 min and it returned to the basal level within 60 min. PD-98059 completely blocked the activation of ERK1/2, the upregulation of 3b-HSD and testosterone production. Our data show that GnRH positively regulates steroidogenesis via ERK signalling in rat Leydig cells. ERK1/2 activation by GnRH may be responsible for the induction of 3b-HSD gene expression and enzyme production, which may ultimately modulate steroidogenesis in rat Leydig cells.

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“…20 Briefly, the testes were isolated and decapsulated. They were then incubated with collagenase type I (0.25 mg ml 21 ) for 20 min at 37 uC.…”

Section: Isolation and Culturing Of Leydig Cellsmentioning

confidence: 99%

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

Yao

Liu²,

Gu³

et al. 2011

Asian J Androl

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“…Leydig cells were prepared from the testes of control and genistein-or procymidone-treated rats by collagenase treatment, as described earlier (Svechnikov et al 2001). Briefly, decapsulated testes were incubated with collagenase (0·25 mg/ml) for 20 min at 37 C, after which the mixture of interstitial cells thus obtained was collected by centrifugation at 300 g for 10 min, followed by washing in HBSS containing 0·1% (w/v) BSA.…”

Section: Isolation and Culture Of Leydig Cellsmentioning

confidence: 99%

Influence of long-term dietary administration of procymidone, a fungicide with anti-androgenic effects, or the phytoestrogen genistein to rats on the pituitary–gonadal axis and Leydig cell steroidogenesis

Svechnikov¹,

Supornsilchai²,

Strand³

et al. 2005

Journal of Endocrinology

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Procymidone is a fungicide with anti-androgenic properties, widely used to protect fruits from fungal infection. Thereby it contaminates fruit products prepared for human consumption. Genistein-containing soy products are increasingly used as food additives with healthpromoting properties. Therefore we examined the effects of long-term dietary administration (3 months) of the anti-androgen procymidone (26·4 mg/animal per day) or the phytoestrogen genistein (21·1 mg/animal per day) to rats on the pituitary-gonadal axis in vivo, as well as on Leydig cell steroidogenesis and on spermatogenesis ex vivo. The procymidone-containing diet elevated serum levels of LH and testosterone and, furthermore, Leydig cells isolated from procymidone-treated animals displayed an enhanced capacity for producing testosterone in response to stimulation by hCG or dibutyryl cAMP, as well as elevated expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450 scc) and cytochrome P450 17 (P450c17). In contrast, the rate of DNA synthesis during stages VIII and IX of spermatogenesis in segments of seminiferous tubules isolated from genistein-treated rats was decreased without accompanying changes in the serum level of either LH or testosterone. Nonetheless, genistein did suppress the ex vivo steroidogenic response of Leydig cells to hCG or dibutyryl cAMP by down-regulating their expression of P450 scc. Considered together, our present findings demonstrate that long-term dietary administration of procymidone or genistein to rats exerts different effects on the pituitarygonadal axis in vivo and on Leydig cell steroidogenesis ex vivo. Possibly as a result of disruption of hormonal feedback control due to its anti-androgenic action, procymidone activates this endocrine axis, thereby causing hypergonadotropic activation of testicular steroidogenesis. In contrast, genistein influences spermatogenesis and significantly inhibits Leydig cell steroidogenesis ex vivo without altering the serum level of either LH or testosterone.

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“…Prevailing observations suggest that IL-1 inhibits both basal and LH/hCG-stimulated testosterone production, and stimulates immature Lydig cell proliferation in in vitro culture. 13 In this study, we examined, by using a real-time PCR, the expression profile of the IL-1 gene superfamily in normal and impaired spermatogenesis, including testicular malignancies, to define whether cytokine gene expression levels differ in various pathophysiological conditions and to establish possible correlations.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1 superfamily genes expression in normal or impaired human spermatogenesis

et al. 2007

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Interleukin-1 (IL-1) is a pleiotropic cytokine that may play a role in contributing to the specific immune environment of mammalian testis and in regulating cell differentiation. We have determined the transcription activity of the IL-1 gene family (using real-time polymerase chain reaction (PCR)) in two main functional testicular compartments (interstitial and intratubular ones), and in tissue homogenates obtained from patients with fertility disorders (spermatogenic arrest and testicular tumors). We observed the prominent expression of gene coding for IL-1 receptor antagonist (IL-1RA) in a purified fraction of gametogenic cells (normal gonad). Caspase-1 (ICE -IL-1b-converting enzyme) was highly expressed (on mRNA level) in interstitial compartments as well in testicular tumors (immune enhancement?). In addition we found, that the activity of IL-1RA gene decreased along spermatogenic alteration in an inversely related manner with IL-1a (from normal gonad through spermatogenic arrest to Sertoli cell only syndrome). Therefore, the quotient value of IL-1a/IL-1RA could potentially serve as the diagnostic molecular probe for spermatogenesis assessment. The precise level of mRNA for IL-1-IL-18 cytokines and their receptors, and specifically of the receptor antagonist in immune privileged gonad, could be one of the main factors responsible for maintaining testicular homeostasis, thus enabling generation of the mature spermatozoa.

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Age-dependent stimulation of Leydig cell steroidogenesis by interleukin-1 isoforms

Cited by 87 publications

References 42 publications

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

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

Influence of long-term dietary administration of procymidone, a fungicide with anti-androgenic effects, or the phytoestrogen genistein to rats on the pituitary–gonadal axis and Leydig cell steroidogenesis

Interleukin-1 superfamily genes expression in normal or impaired human spermatogenesis

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