Molecular and cellular endocrinology
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Mol. Cell. Endocrinol. · Mar 2014
Insulin-like growth factor I induces proliferation and migration of porcine trophectoderm cells through multiple cell signaling pathways, including protooncogenic protein kinase 1 and mitogen-activated protein kinase.
During early pregnancy, the developing conceptus is dependent upon a wide range of growth factors and nutrients that are secreted by or transported by uterine epithelia into the uterus at the maternal-conceptus interface for successful implantation and placentation. Among these factors, insulin-like growth factor-I (IGF-I) is known to play an important role in development of the early embryo and uterine endometrium. However, few studies have been conducted with pigs to determine IGF-I-induced functional effects on peri-implantation embryos such as activation of cell signaling cascades responsible for growth, proliferation and differentiation of cells of the conceptus. ⋯ In the presence of the ERK1/2 MAPK inhibitor (U0126), IGF-I-induced AKT1 phosphorylation was not affected, whereas the PI3K inhibitor (LY294002) decreased IGF-I-induced phosphorylation of ERK1/2 and AKT1 proteins, and both the PI3K-AKT1 and ERK1/2 MAPK pathways were blocked by LY294002. Furthermore, IGF-I significantly stimulated both proliferation and migration of pTr cells, but these effects were blocked by P38 inhibitor (SB203580), U0126, MTOR inhibitor (rapamycin) and LY294002. Taken together, these results indicate that IGF-I coordinately regulates multiple cell signaling pathways including PI3K-AKT1-RPS6 and ERK1/2 MAPK signaling pathways that are critical to proliferation, migration and survival of trophectoderm cells during early pregnancy in pigs.
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Mol. Cell. Endocrinol. · Mar 2014
Nonalcoholic steatohepatitis as a novel player in metabolic syndrome-induced erectile dysfunction: an experimental study in the rabbit.
A pathogenic link between erectile dysfunction (ED) and metabolic syndrome (MetS) is now well established. Nonalcoholic steatohepatitis (NASH), the hepatic hallmark of MetS, is regarded as an active player in the pathogenesis of MetS-associated cardiovascular disease (CVD). This study was aimed at evaluating the relationship between MetS-induced NASH and penile dysfunction. ⋯ T and OCA dosing in HFD rabbits both reduced TNFα liver expression and plasma levels, with a parallel increase of penile eNOS expression and responsiveness to Ach. Also neutralization of TNFα with infliximab treatment fully normalized HFD-induced hypo-responsiveness to Ach, as well as responsiveness to vardenafil, a phosphodiesterase type 5 inhibitor. Thus, MetS-induced NASH in HFD rabbits plays an active role in the pathogenesis of ED, likely through TNFα, as indicated by treatments reducing liver and circulating TNFα levels (T or OCA), or neutralizing TNFα action (infliximab), which significantly improve penile responsiveness to Ach in HFD rabbits.
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Mol. Cell. Endocrinol. · Feb 2014
Differential involvement of signaling pathways in the regulation of growth hormone release by somatostatin and growth hormone-releasing hormone in orange-spotted grouper (Epinephelus coioides).
Somatostatin is the most effective inhibitor of GH release, and GHRH was recently identified as one of the primary GH-releasing factors in teleosts. In this study, we analyzed the possible intracellular transduction pathways that are involved in the mechanisms induced by SRIF and GHRH to regulate GH release. Using a pharmacological approach, the blockade of the PLC/IP/PKC pathway reversed the SRIF-induced inhibition of GH release but did not affect the GHRH-induced stimulation of GH release. ⋯ In addition, inhibitors of the sGC/cGMP pathway did not modify the SRIF- or GHRH-induced regulation of GH release. Taken together, these findings indicate that the SRIF-induced inhibition of GH release is mediated by both the PLC/IP/PKC and the AC/cAMP/PKA pathways and not by the NOS/NO/sGC/cGMP pathway. In contrast, the GHRH-induced stimulation of GH secretion is mediated by both the AC/cAMP/PKA and the NOS/NO pathways and is independent of the sGC/cGMP pathway and the PLC/IP/PKC system.
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Mol. Cell. Endocrinol. · Jan 2014
ReviewGenome-wide association studies of age at menarche and age at natural menopause.
Genome-wide association studies (GWAS) have been successful in uncovering genetic determinants of age at menarche and age at natural menopause. To date, more than 30 novel genetic loci have been identified in GWAS for age at menarche and 17 for age at natural menopause. ⋯ This review provides an overview of the current state of our knowledge of the genetic basis of menarche and menopause timing. It emphasizes recent GWAS results and outlines strategies for discovering the missing heritability and strategies to further our understanding of the underlying molecular mechanisms of the observed genetic associations.
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Mol. Cell. Endocrinol. · Aug 2013
Oleanolic acid improves hepatic insulin resistance via antioxidant, hypolipidemic and anti-inflammatory effects.
Insulin resistance is the hallmark of type 2 diabetes mellitus (T2DM), which is closely related to disorder of lipid metabolism. The study was designed to evaluate the effects of oleanolic acid (OA) on hepatic insulin resistance and underlying mechanisms in Lep(db)(/)(db) obese diabetic mice. db/db Mice were administered with OA (20mg/kg/day, i.p.) for two weeks. OA reduced body weight, liver weight, and fat weight, and protected liver morphology and function. ⋯ Furthermore, inflammatory condition in db/db mice was improved by OA, as evidenced by decreased level of IL-1 β, IL-6, and TNFα in circulation and in liver. The evidence suggests that OA improves hepatic insulin resistance through inhibition of mitochondrial ROS, hypolipidemic and anti-inflammatory effects. The effectiveness of OA leads to interesting therapeutic perspectives.