scholarly journals Activation of the Lutropin/Choriogonadotropin Receptor Inhibits Apoptosis of Immature Leydig Cells in Primary Culture

Endocrinology ◽  
2009 ◽  
Vol 150 (8) ◽  
pp. 3766-3773 ◽  
Author(s):  
Ping Tai ◽  
Koji Shiraishi ◽  
Mario Ascoli
Keyword(s):  
Leydig Cells ◽  
Thymidine Incorporation ◽  
Primary Cultures ◽  
Drug Induced ◽  
Immature Rat ◽  
Akt Phosphorylation ◽  
Igf I ◽  
Epidermal Growth ◽  
Induced Apoptosis ◽  
Stimulation Of

We used proliferating primary cultures of immature rat Leydig cells expressing the recombinant human LH/choriogonadotropin (CG) receptor (LHR) to test the hypothesis that activation of this receptor inhibits apoptosis. We also compared the effects of LH/CG with epidermal growth factor (EGF) and IGF-I because these have been previously shown to stimulate proliferation and/or inhibit apoptosis in Leydig cells. Human CG (hCG), EGF, and IGF-I stimulated the phosphorylation of ERK1/2 and Akt in primary cultures of immature rat Leydig cells. These three hormones also robustly stimulated thymidine incorporation and inhibited drug-induced apoptosis. Using selective inhibitors of ERK1/2 (UO126) or Akt phosphorylation (LY294002), we show that the ERK1/2 and Akt cascades are both involved in the hCG- and EGF-dependent proliferation of Leydig cells, but only the ERK1/2 cascade is involved in their antiapoptotic actions. The same strategy showed that the proliferative and antiapoptotic actions of IGF-I are mediated entirely by the Akt pathway. These results show that activation of the LHR inhibits apoptosis in Leydig cells and that it does so through stimulation of the ERK1/2 pathway.

Normal somatomedin-C/insulin-like growth factor I binding and action in cultured human fibroblasts from Turner syndrome

1983 ◽  
Vol 104 (4) ◽  
pp. 502-509 ◽  
Author(s):  
Ron G. Rosenfeld ◽  
Laura A. Dollar ◽  
Raymond L. Hintz ◽  
Cheryl Conover
Keyword(s):  
Growth Factor ◽  
Turner Syndrome ◽  
Thymidine Incorporation ◽  
Insulin Like Growth Factor ◽  
Cell Replication ◽  
Somatomedin C ◽  
Factor I ◽  
Igf I ◽  
And Control ◽  
Stimulation Of

Abstract. Growth retardation is a major manifestation of Turner syndrome (TS). Since plasma growth hormone and somatomedin-C/insulin-like growth factor I (SM-C/IGF-I) levels are generally normal, growth failure has been ascribed to peripheral defects in SM-C/IGF-I receptors or action. We have measured the binding of [125I]SM-C/IGF-I to cultured fibroblast monolayers derived from patients with Turner syndrome, and have evaluated SM-C/IGF-I stimulation of both [3H]thymidine incorporation and cell replication. When compared to fibroblasts from normal adults, newborns, and agematched children, no significant differences were observed in specific binding of [125I]SM-C/IGF-I to fibroblast monolayers, and displacement curves demonstrated similar receptor affinities for all groups. Similarly, equivalent SM-C/IGF-I stimulation of [3H]thymidine incorporation was seen in both Turner and control fibroblasts. In the absence of serum, SM-C/IGF-I, at a concentration of 10–25 ng/ml, stimulated thymidine incorporation 3.7–11.8-fold in Turner fibroblasts and 1.9–9.8-fold in control cells. In combination with 1.0% human hypopituitary serum (HHS), SM-C/IGF-I stimulated thymidine incorporation 20–70-fold in all cell lines. Cell replication in both TS and control cells was increased 90% by the combination of SM-C/IGF-I + 0.5% HHS, and 140% by SM-C/IGF-I + 0.5% HHS + dexamethasone. We conclude that TS fibroblasts have normal SM-C/IGF-I receptors and sensitivity, and are capable of enhanced DNA synthesis and replication following SM-C/IGF-I stimulation.

Stimulation of intestinal epithelial cell proliferation in culture by growth factors in human and ruminant mammary secretions

1987 ◽  
Vol 113 (2) ◽  
pp. 285-290 ◽  
Author(s):  
A. N. Corps ◽  
K. D. Brown
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Intestinal Epithelial ◽  
Epithelial Cell Proliferation ◽  
Factor I ◽  
Maximal Stimulation ◽  
Igf I ◽  
Epidermal Growth ◽  
Dose Dependent ◽  
Stimulation Of

ABSTRACT Samples of human and ruminant mammary secretions stimulated the proliferation of rat intestinal epithelial (RIE-1) cells in culture. The stimulation was dose-dependent, and samples taken prepartum had greater potency than those taken after parturition. When various hormones and growth factors known to be present in milk were tested, only epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I) stimulated the proliferation of RIE-1 cells. IGF-I was effective at lower concentrations than insulin, and the maximal stimulation induced by each of these two polypeptides was greater than that induced by EGF. The maximal stimulation induced by samples of mammary secretions was similar to that induced by insulin or IGF-I. J. Endocr. (1987) 113, 285–290

Paracrine effects via the epidermal growth factor receptor in the rodent testis may be mediated by non-Leydig interstitial cells

1993 ◽  
Vol 136 (3) ◽  
pp. 439-NP ◽  
Author(s):  
A. Moore ◽  
I. D. Morris
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Interstitial Cell ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Thymidine Incorporation ◽  
Buoyant Density ◽  
Epidermal Growth

ABSTRACT The epidermal growth factor (EGF) receptor is expressed in a wide variety of cell types and is known to be present in the testis of many species including man. In the present study, specific 125 I-labelled EGF binding was observed in isolated interstitial cell preparations from both the intact and Leydig cell-depleted rat testis. It was demonstrated that the population of cells to which 125I-labelled EGF binds has a different buoyant density from either of the two adult Leydig cell populations, and remains unchanged in the absence of Leydig cells following in-vivo treatment with ethane dimethane sulphonate (EDS). Cells of this density (1·064 g/ml) identified by electron microscopy were fusiform mesenchymal cells, identical to those suggested by others to be able to differentiate into Leydig cells in vitro, i.e. Leydig cell precursors. In a culture system using two interstitial cell preparations of different buoyant densities from immature rats, both EGF and transforming growth factor-α (TGF-α) caused increased [3H]thymidine incorporation in the less dense cell preparation. TGF-α was more potent than EGF. EGF increased testosterone production in both fractions in amounts which could be related to the amount of 3β-hydroxysteroid dehydrogenase (3β-HSD)-positive cells. This study demonstrated that rat Leydig cells (defined as those cells which bind 125I-labelled human chorionic gonadotrophin, have distinct buoyant densities, are 3β-HSD positive and are sensitive to EDS), do not bind 125I-labelled EGF. Rather, EGF binds to a mesenchymal cell without LH receptors which is resistant to EDS. Growth factors which act via the EGF receptor increased [3H]thymidine incorporation in a Leydig cell-depleted interstitial fraction which may reflect an action upon the progenitor of the mature Leydig cell. Journal of Endocrinology (1993) 136, 439–446

Effect of epidermal growth factor on magnesium homeostasis in BC3H1 myocytes

1991 ◽  
Vol 260 (6) ◽  
pp. C1158-C1164 ◽  
Author(s):  
R. D. Grubbs
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Thymidine Incorporation ◽  
Dose Dependence ◽  
Acute Effects ◽  
Cellular Regulation ◽  
Magnesium Homeostasis ◽  
Epidermal Growth ◽  
Fold Stimulation ◽  
Stimulation Of

The acute effects of epidermal growth factor (EGF) on Mg2+ homeostasis were studied in differentiated BC3H1 myocytes. EGF produced a 48-fold stimulation of [3H]thymidine incorporation into quiescent serum-starved cells in the presence of Mg2+, whereas insulin had no effect on [3H]thymidine incorporation. The dose dependence of EGF-stimulated [3H]thymidine incorporation was similar to that of EGF stimulation of 28Mg2+ uptake. In cells loaded with the Mg(2+)-sensitive fluorescent indicator, Mag-fura-2, intracellular Mg2+ concentration ([Mg2+]i) increased after exposure to EGF after a 5-min lag; a similar lag was routinely observed before the stimulation of 28Mg2+ uptake by EGF. In control studies, cytosolic free Ca2+ levels and intracellular pH (pHi) were unchanged during 20 min of exposure to EGF. These results suggest that [Mg2+]i in BC3H1 cells is regulated by EGF. This regulation is not mediated by changes in pHi or intracellular Ca2+ concentration and may constitute an important event in the physiological response of these cells to EGF. The results are discussed within the context of cellular regulation of Mg2+ homeostasis.

RETRACTED: Stimulation of sensory neurons by capsaicin increases tissue levels of IGF-I, thereby reducing reperfusion-induced apoptosis in mice

2007 ◽  
Vol 52 (5) ◽  
pp. 1303-1311 ◽  
Author(s):  
Naoaki Harada ◽  
Kenji Okajima ◽  
Hiroki Kurihara ◽  
Naomi Nakagata
Keyword(s):  
Sensory Neurons ◽  
Tissue Levels ◽  
Igf I ◽  
Induced Apoptosis ◽  
Stimulation Of

scholarly journals ANG II induces apoptosis of human vascular smooth muscle via extrinsic pathway involving inhibition of Akt phosphorylation and increased FasL expression

2006 ◽  
Vol 290 (5) ◽  
pp. H2116-H2123 ◽  
Author(s):  
Yangxin Li ◽  
Yao-Hua Song ◽  
Jessica Mohler ◽  
Patrick Delafontaine
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Caspase 8 ◽  
Ang Ii ◽  
Fasl Expression ◽  
Akt Phosphorylation ◽  
Marked Inhibition ◽  
Soluble Fasl ◽  
Induced Apoptosis ◽  
Stimulation Of

In addition to well-documented vascular growth-promoting effects, ANG II exerts proapoptotic effects that are poorly understood. IGF-1 is a potent survival factor for human vascular smooth muscle cells (hVSMC), and its antiapoptotic effects are mediated via the IGF-1 receptor (IGF-1R) through a signaling pathway involving phosphatidylinositol 3-kinase and Akt. We hypothesized that there would be cross talk between ANG II proapoptotic effects and IGF-1 survival effects in hVSMC. To investigate ANG II-induced apoptosis and the potential involvement of IGF-1, we exposed quiescent and nonquiescent hVSMC to ANG II. ANG II induced apoptosis only in nonquiescent cells but stimulated hypertrophy in quiescent cells. ANG II-induced apoptosis was characterized by marked inhibition of Akt phosphorylation and stimulation of membrane Fas ligand (FasL) expression, caspase-8 activation, and a reduction in soluble FasL expression. Adenovirally mediated overexpression of Akt rescued hVSMC from ANG II-induced apoptosis. IGF-1R activation increased Akt phosphorylation and soluble FasL expression, and these effects were completely blocked by coincubating hVSMC with ANG II. In conclusion, ANG II-induced apoptosis of hVSMC is characterized by marked inhibition of Akt phosphorylation and stimulation of an extrinsic cell death signaling pathway via upregulation of membrane FasL expression, caspase-8 activation, and a reduction in soluble FasL expression. Furthermore, ANG II antagonizes the antiapoptotic effect of IGF-1 by blocking its ability to increase Akt phosphorylation and soluble FasL. These findings provide novel insights into ANG II-induced apoptotic signaling and have significant implication for understanding ANG II-induced remodeling in hypertension and atherosclerosis.

scholarly journals Lutropin/Choriogonadotropin Stimulate the Proliferation of Primary Cultures of Rat Leydig Cells through a Pathway that Involves Activation of the Extracellularly Regulated Kinase 1/2 Cascade

Endocrinology ◽  
2007 ◽  
Vol 148 (7) ◽  
pp. 3214-3225 ◽  
Author(s):  
Koji Shiraishi ◽  
Mario Ascoli
Keyword(s):  
Leydig Cells ◽  
Proliferative Response ◽  
Recombinant Adenovirus ◽  
Inositol Phosphate ◽  
Primary Cultures ◽  
Steroid Biosynthesis ◽  
Immature Rat ◽  
Phosphate Accumulation ◽  
Inositol Phosphate Accumulation ◽  
Immature Cells

Primary cultures of progenitor and immature rat Leydig cells were established from the testes of 21- and 35-d-old rats, respectively. The cell population remained homogeneous after 4–6 d in culture as judged by staining for 3β-hydroxysteroid dehydrogenase, but the cells were unable to bind 125I-human chorionic gonadotropin (hCG) or to respond to hCG with classical LH receptor (LHR)-mediated responses, including cAMP and inositol phosphate accumulation, steroid biosynthesis, or the phosphorylation of ERK1/2. Infection of primary cultures with recombinant adenovirus coding for β-galactosidase showed that approximately 65% of the cells are infected. Infection with adenovirus coding for the human LHR (hLHR) allowed for expression of the hLHR at a density of approximately 25,000 receptors per cell and allowed the cells to respond to hCG with increases in cAMP and inositol phosphate accumulation, steroid biosynthesis, and the phosphorylation of ERK1/2. Although progenitor and immature cells were able to respond to hCG with an increase in progesterone, only the immature cells responded with an increase in testosterone. In addition to these classical LHR-mediated responses, the primary cultures of progenitor or immature rat Leydig cells expressing the recombinant hLHR proliferated robustly when incubated with hCG, and this proliferative response was sensitive to an inhibitor of ERK1/2 phosphorylation. These studies establish a novel experimental paradigm that can be used to study the proliferative response of Leydig cells to LH/CG. We conclude that activation of the LHR-provoked Leydig cell proliferation requires activation of the ERK1/2 cascade.

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