Aldo Keto Reductase 1B7 and Prostaglandin F2α Are Regulators of Adrenal Endocrine Functions

Prostaglandin F2α (PGF2α), represses ovarian steroidogenesis and initiates parturition in mammals but its impact on adrenal gland is unknown. Prostaglandins biosynthesis depends on the sequential action of upstream cyclooxygenases (COX) and terminal synthases but no PGF2α synthases (PGFS) were functionally identified in mammalian cells. In vitro, the most efficient mammalian PGFS belong to aldo-keto reductase 1B (AKR1B) family. The adrenal gland is a major site of AKR1B expression in both human (AKR1B1) and mouse (AKR1B3, AKR1B7). Thus, we examined the PGF2α biosynthetic pathway and its functional impact on both cortical and medullary zones. Both compartments produced PGF2α but expressed different biosynthetic isozymes. In chromaffin cells, PGF2α secretion appeared constitutive and correlated to continuous expression of COX1 and AKR1B3. In steroidogenic cells, PGF2α secretion was stimulated by adrenocorticotropic hormone (ACTH) and correlated to ACTH-responsiveness of both COX2 and AKR1B7/B1. The pivotal role of AKR1B7 in ACTH-induced PGF2α release and functional coupling with COX2 was demonstrated using over- and down-expression in cell lines. PGF2α receptor was only detected in chromaffin cells, making medulla the primary target of PGF2α action. By comparing PGF2α-responsiveness of isolated cells and whole adrenal cultures, we demonstrated that PGF2α repressed glucocorticoid secretion by an indirect mechanism involving a decrease in catecholamine release which in turn decreased adrenal steroidogenesis. PGF2α may be regarded as a negative autocrine/paracrine regulator within a novel intra-adrenal feedback loop. The coordinated cell-specific regulation of COX2 and AKR1B7 ensures the generation of this stress-induced corticostatic signal

Contrôle hormonal du métabolisme hépatique chez les ruminants

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Differential regulation of muscle and liver insulin receptors by energy restriction in growing rats

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Androgens regulate expression of the gene coding for a mouse vas deferens protein related to the aldo-keto reductase superfamily in epithelial cell subcultures

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Identification of a functional androgen response element in the promoter of the gene for the androgen-regulated aldose reductase-like protein specific to the mouse vas deferens

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Androgen receptor expression is regulated by the phosphoinositide 3-kinase/Akt pathway in normal and tumoral epithelial cells.

The androgen receptor (AR) is a ligand-responsive transcription factor known to play a central role in the pathogenesis of prostate cancer. However, the regulation of AR gene expression in the normal and pathological prostate remains poorly understood. This study focuses on the effect of the phosphoinositide 3-kinase (PI 3-kinase)/Akt axis on AR expression in vas deferens epithelial cells (VDEC), a suitable model to study androgen regulation of gene expression, and LNCaP cells (derived from a metastasis at the left supraclavicular lymph node from a 50-year-old patient with a confirmed diagnosis of metastatic prostate carcinoma). Taken together, our data show for the first time that the PI 3-kinase/Akt pathway is required for basal and dihydrotestosterone-induced AR protein expression in both VDEC and LNCaP. Inhibition of the PI 3-kinase/Akt pathway reduced AR expression and the decline in AR protein level correlated with a decrease in AR mRNA in VDEC but not in LNCaP. Since PI 3-kinase/Akt axis is active in prostate cancer, cross-talk between PI 3-kinase/Akt and AR signalling pathways may have implications for endocrine therapy

Metal-NHC complexes: a survey of anti-cancer properties

International audienceNew weapons to fight cancer are constantly needed. Among chemotherapeutics, anti-cancer metal-drugs have enjoyed a long and successful history since the discovery of the benchmark cisplatin. Advances in metal-drug discovery have motivated chemists to build plethora of complex structures. Among them, a novel area is emerging. This article presents a survey of the metal-N-Heterocyclic Carbenes (Ag(I), Au(I), Pd(II) and Cu(I)-NHCs) as potential anti-cancer agents. Most of the metal-NHCs considered display higher cytotoxicities than the reference metallo-drug cisplatin. Some of them are even selective for particular cell lines. Their mechanisms of action at the cellular level are further discussed, showing that the nature of the metal is of great importance. All these promising results demonstrate that this approach deserves more attention and work

Role of PGF_2α in adrenal endocrine functions.

<p><i>A</i>, ELISA quantification of PGF_2α release by chromaffin MPC862L cells untreated (control) or treated with 10⁻⁶ M dexamethasone for 12 h (dex). <i>B</i>, HPLC quantification of dopamine secretion by MPC862L cells cultured in absence or presence of 10⁻⁷ M cloprostenol (clo) (PGF_2α analogue) used either alone or in combination with 10⁻⁶ M dexamethasone for 12 h (clo+dex). Values are the mean of 3 experiments ± S.D. *, <i>P</i><0.05, ** <i>P</i><0.01. <i>C</i>, Typical perifusion profiles illustrating the effects of increasing concentrations of PGF_2α (0.1 µM to 10 µM) and cloprostenol (0.1 nM to 1 µM) on corticosterone secretion. Horizontal bars indicate the start point and duration of PGF_2α or cloprostenol infusions. <i>D</i>, Semi-logarithmic plot showing the effect of increasing concentrations of PGF_2α and cloprostenol on the inhibition of corticosterone secretion. Results are expressed as a percentage of the basal secretory rate. Experimental values were calculated from data similar to those presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007309#pone-0007309-g005" target="_blank">Fig. 5</a><i>C</i>. Each curve represents the mean ± SEM of 6 to 12 independent experiments. After stabilization, the mean secretion rate of corticosterone in basal condition was 251±14 pg/min per adrenal. The concentration-response curve was fitted using the Prism program (GraphPad Software, Inc., San Diego, CA). **<i>P<0.001</i>.</p