The Journal of steroid biochemistry and molecular biology
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J. Steroid Biochem. Mol. Biol. · Sep 2014
Early repeated administration of progesterone improves the recovery of neuropathic pain and modulates spinal 18kDa-translocator protein (TSPO) expression.
Although progesterone was reported to be a neuroprotective agent against injuries to the nervous system, including the peripheral neuropathy, the mechanisms of its dose or timing-related effects remain unclear. Translocator protein (TSPO) is predominantly located in the mitochondrial outer membrane and has been recently implicated in modulation of several brain injuries and nociception. This experiment was conducted using a rat model of L5 spinal nerve ligation (SNL) to observe the effects of progesterone against allodynia development in an 84-day period and to explore the spinal TSPO expression after treatment. ⋯ A treatment regimen of pharmacological progesterone augmented this spinal TSPO activation and expression before Day 28 and after Day 56. Both the anti-nociception and TSPO activation augment effect of progesterone were completely abolished by 5α-reductase inhibitor finasteride but not progesterone receptor antagonist mifepristone. These results indicate that early repeated administration of progesterone could improve the recovery of neuropathic pain and modulate spinal TSPO activation which were dependent on its 5α-reductase metabolites.
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J. Steroid Biochem. Mol. Biol. · Sep 2014
Estrogen activation of the mitogen-activated protein kinase is mediated by ER-α36 in ER-positive breast cancer cells.
It is well known that there are two estrogen-signaling pathways, genomic estrogen signaling and non-genomic or rapid estrogen signaling. Although both ER-α and ER-β have been suggested to mediate both genomic and non-genomic estrogen signaling, rapid estrogen signaling such as activation of the MAPK/ERK signaling in ER-positive breast cancer MCF7 cells has been controversial. Previously, our laboratory cloned a 36kDa variant of ER-α, ER-α36, that is mainly localized at the plasma membrane and is able to mediate rapid estrogen signaling. ⋯ We found that ER-α36 mediated estrogen induction of the MAPK/ERK phosphorylation in ER-positive breast cancer cells while the full-length ER-α failed to do so. The rapid estrogen signaling mediated by ER-α36 involved a orchestrated action of matrix metalloproteinases (MMPs), heparin-binding epidermal growth factor (HB-EGF), amphiregulin, insulin-like growth factor 1 receptor (IGF-1R), epidermal growth factor receptor (EGFR), HER2/Neu and Src. Our results thus indicated that ER-α36 is the estrogen receptor that mediates estrogen induction of the MAPK/ERK signaling in ER-positive breast cancer cells.
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J. Steroid Biochem. Mol. Biol. · Sep 2014
Estradiol-potentiated cadherin-11 in synovial membrane involves in temporomandibular joint inflammation in rats.
Estrogen is involved in inflammation/pain of temporomandibular joint (TMJ), but the underlying mechanisms are largely unknown. Cadherin-11 plays an essential role in synovial inflammation. This study examined whether estrogen could potentiate cadherin-11 in synoviocytes and contribute to TMJ inflammatory pain. ⋯ Blocking cadherin-11 partially reversed the TMJ inflammatory pain and estradiol-potentiated proliferation of synovial lining cells accompanied with iNOS expression. In addition, blocking cadherin-11 reversed TNF-α-induced and estradiol-potentiated transcription of IL-6, COX-2, and iNOS in primary synoviocytes. These results suggest that estrogen aggravated TMJ inflammatory pain partially through cadherin-11-mediated release of proinflammatory cytokines and enzymes in the synoviocytes.
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J. Steroid Biochem. Mol. Biol. · Sep 2014
Multicenter Study Observational StudySerum lipoprotein composition and vitamin D metabolite levels in clinically isolated syndromes: Results from a multi-center study.
High serum cholesterol is adversely associated with clinical and imaging disease progression outcomes in multiple sclerosis (MS) and in clinically isolated syndrome (CIS), the earliest stage of MS. Low vitamin D levels are associated with an increased risk of disease progression. ⋯ The associations between cholesterol biomarkers and vitamin D metabolite levels in CIS are consistent with the biochemical inter-dependence between the two pathways. Cholesterol biomarkers should be considered for inclusion as covariates when assessing vitamin D levels in CIS.
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J. Steroid Biochem. Mol. Biol. · Sep 2014
Melatonin pretreatment prevented the effect of dexamethasone negative alterations on behavior and hippocampal neurogenesis in the mouse brain.
Glucocorticoids play various physiological functions via the glucocorticoid receptor (GR). Glucocorticoid is associated with the pathophysiology of depression. Dexamethasone (DEX), a synthetic GR agonist, has a greater affinity for GR than the mineralocorticoid receptor (MR) in the hippocampus of pigs and may mimic the effects of GR possession. ⋯ Melatonin may protect hippocampal neurons from damage and reverse neurogenesis after chronic DEX by activating brain-derived neurotrophic (BDNF) and ERK1/2 cascades. These results revealed that melatonin pretreatment prevented the reduction of cell proliferation, immature neuron precursor cells, and GR and ERK1/2 expression. This finding indicates that melatonin attenuates the DEX-induced depressive-like behavior, supporting the notion that melatonin possesses anti-stress and neurogenic actions.