Projects per year
Abstract / Description of output
Methods: A randomised double-blind crossover study was conducted in 14 healthy men comparing placebo and ABCC1 inhibitor probenecid. Blood sampling, including from veins draining adipose and muscle, was undertaken before and after administration of mineralocorticoid receptor antagonist potassium canrenoate and glucocorticoid receptor antagonist mifepristone (RU486).
Results: During placebo, systemic plasma cortisol and corticosterone concentrations increased promptly after canrenoate. Cortisol uptake was detected from adipose but not muscle following canrenoate+RU486. Probenecid significantly increased systemic cortisol concentrations, and tended to increase corticosterone and ACTH concentrations, after combined receptor antagonism but had no effects on net glucocorticoid balance in either adipose or muscle. Using quantitative PCR in brain bank tissue, ABCC1 expression was 5-fold higher in human pituitary than hypothalamus and hippocampus. ABCB1 was more highly expressed in hypothalamus compared to pituitary.
Conclusions: Although displacement of corticosterone and/or cortisol from receptors in adipose and skeletal muscle could not be measured with sufficient precision to detect effects of probenecid, ABCC1 inhibition induced a greater incremental activation of the hypothalamic-pituitary-adrenal axis after combined receptor blockade, consistent with ABCC1 exporting corticosterone from the pituitary and adding to the evidence that ABC transporters modulate tissue glucocorticoid sensitivity.
Keywords / Materials (for Non-textual outputs)
- ABC transporters
- Adipose tissue
- HPA axis
- Skeletal muscle
FingerprintDive into the research topics of 'ABCC1 modulates negative feedback control of the hypothalamic-pituitary-adrenal axis in vivo in humans'. Together they form a unique fingerprint.
- 3 Finished
1/02/16 → 30/06/22
Tissue specific determinants of glucocorticoid signalling in humans - new mechanisms and therapies for cardiovascular risk. (Renewal: YYRS 11-15)
1/04/11 → 31/03/16
Centre for Cardiovascular Science