FROM TALK TO ACTION: POLICY STAKEHOLDERS, APPROPRIATENESS, AND SELECTIVE DISINVESTMENT

OBJECTIVES: There is widespread commitment--at least in principle--to "evidence-informed" clinical practice and policy development in health care. The intention is that only "appropriate" care ought to be delivered at public expense. Although the rationale for an appropriateness agenda is widely endorsed, and methods have been proposed for addressing it, few published studies exist of contemporary policy initiatives which have actually led to successful disinvestment. Our objective was to explore whether the direct involvement of policy stakeholders could advance appropriateness and disinvestment. METHODS: Several collaborative engagements with policy stakeholders were undertaken to adapt and combine conceptual and empirical material related to appropriateness and disinvestment from the literature to create tools and processes for use in Canada and the province of Ontario in particular. RESULTS: By combining inputs from the literature with colloquial evidence from policy stakeholders, a definition of appropriateness was developed and, importantly, endorsed by all the provincial and territorial ministers of health in Canada. Second, a reassessment framework was successfully implemented for identifying priorities for selective disinvestment. CONCLUSIONS: When scientific evidence was combined with colloquial evidence from policy stakeholders, progress was made on the design and successful implementation of policies for appropriateness and disinvestment

A novel non genomic glucocorticoid signaling mediated by a membrane palmitoylated glucocorticoid receptor cross talks with GnRH in gonadotrope cells

International audienceGlucocorticoid hormones (GC) are the main stress mediators associated with reproductive disorders. GC exert their effects through activation of the glucocorticoid receptor (GR) principally acting as a transcription factor. Beside well-established GR-mediated genomic actions, several lines of evidence suggest a role for rapid membrane-initiated GC signaling in gonadotrope cells triggered by a membrane-associated GR. Herein, we demonstrate the existence of a specific membrane-initiated GC signaling in L beta T2 gonadotrope cells involving two related phosphoproteins: Ca2+/Calmodulin-dependent protein kinase II (CaMKII) and synapsin-I. Within 5 min, L beta T2 cells treated with stress range of 10(-7) M Corticosterone or a membrane impermeable-GC, BSA-conjugated corticosterone, exhibited a 2-fold increase in levels of phospho-CaMKII and phospho-synapsin-I. Biochemical approaches revealed that this rapid signaling is promoted by a palmitoylated GR. Importantly, GC significantly alter GnRH-induced CaMKII phosphorylation, consistent with a novel cross-talk between the GnRH receptor and GC. This negative effect of GC on GnRH signaling was further observed on LH release by mouse pituitary explants. Altogether, our work provides new findings in GC field by bringing novel understanding on how GR integrates plasma membrane, allowing GC membrane-initiated signaling that differs in presence of GnRH to disrupt GnRH-dependent signaling and LH secretion