ISSN 1662-4009 (online)

ey0015.8-4 | New Mechanisms | ESPEYB15

8.4 Dynamic responses of the adrenal steroidogenic regulatory network

F Spiga , E Zavala , JJ Walker , Z Zhao , JR Terry , SL Lightman

To read the full abstract: Proc Natl Acad Sci U S A. 2017; 114(31): E6466-E6474Cortisol production is tightly regulated in a dynamic way within the hypothalamic-pituitary adrenal system, which seems further embedded in a wider steroidogenic regulatory network (SRN). Normally, the connection from ACTH to cortisol production is in line with the HPA axis, but there are stressful events, in which t...

ey0015.8-3 | New Mechanisms | ESPEYB15

8.3 Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man

K Kalafatakis , GM Russell , CJ Harmer , MR Munafo , N Marchant , A Wilson , JC Brooks , C Durant , J Thakrar , P Murphy , NJ Thai , SL Lightman

To read the full abstract: Proc Natl Acad Sci U S A. 2018; 115(17): E4091-E4100The hypothalamic-pituitary-adrenal axis is a critical neurohormonal network that regulates homeostasis and coordinates the stress response. Glucocorticoids (GCs) are critical for life and are key regulators of cognitive, metabolic and immunologic homeostasis (4). Clinical studies in healthy human subjects, usi...

ey0020.6-2 | New Mechanisms | ESPEYB20

6.2. Circadian regulation of hippocampal function is disrupted with corticosteroid treatment

MT Birnie , MDB Claydon , O Troy , BP Flynn , M Yoshimura , YM Kershaw , Z Zhao , RCR Demski-Allen , GRI Barker , EC Warburton , ZA Bortolotto , SL Lightman , BL Conway-Campbell

Brief summary: This study investigates the effect of long-acting synthetic glucocorticoids on circadian rhythmicity and hippocampal functionGlucocorticoids exert their effects by binding to glucocorticoid receptors (GRs), which regulate up to ~20% of the genome via both direct (by binding to glucocorticoid responsive elements in promoter regions) and indirect mechanisms (by interacting with bound transcription factors and epigenetic modifiers) (1...

ey0021.8-5 | Important for Clinical Practice | ESPEYB21

8.5. High-resolution daily profiles of tissue adrenal steroids by portable automated collection

TJ Upton , E Zavala , P Methlie , O Kampe , S Tsagarakis , M Oksnes , S Bensing , DA Vassiliadi , MA Grytaas , IR Botusan , G Ueland , K Berinder , K Simunkova , M Balomenaki , D Margaritopoulos , N Henne , R Crossley , G Russell , ES Husebye , SL Lightman

Brief Summary: This paper describes a novel ambulatory fraction collector that can be used with microdialysis to obtain high resolution steroid profiles over a 24-hour period.Comment: The natural circadian and ultradian secretion of adrenal hormones makes single timepoint measurements of these hormones uninformative for clinical decision making (1-3). Repeated sampling during the day requires admission into an atypical, and often disruptive, clinical set...

ey0021.8-12 | Clinical Trials – New Treatments | ESPEYB21

8.12. Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: the PULSES trial

G Russell , K Kalafatakis , C Durant , N Marchant , J Thakrar , R Thirard , J King , J Bowles , T Upton , NJ Thai , JCW Brooks , A Wilson , K Phillips , S Ferguson , M Grabski , CA Rogers , T Lampros , S Wilson , C Harmer , M Munafo , SL Lightman

Brief Summary: This 6-week randomized, crossover, double blind, placebo-controlled feasibility trial assessed the effect of subcutaneous pump hydrocortisone on the quality of life, mood, functional neuroimaging, behavioral/cognitive responses, sleep and metabolism in adults with primary adrenal insufficiency (PAI) compared to standard therapy.Comment: Adrenal glucocorticoid secretion is characterized by a complex diurnal variation, formed by changes in p...