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Title: Purinergic regulation of steroid secretion in the bovine adrenal cortex (inner zone)
Author: Hoey, D. E. Elaine
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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The aims of this thesis were: a) to investigate the mechanisms by which ATP, adenosine and other purines stimulate cortisol secretion from bovine adrenal zfr cells maintained in primary culture, b) to study the interaction of ATP with the other adrenocortical hormones and finally c) to investigate the acute and chronic effects of ACTH, AII and ATP on the regulation of the steroidogenic pathway. The purinergic agonists ATP and ADP stimulated cortisol secretion in a dose-dependent manner in both freshly-isolated and cultured cells (ATP:Emax( the maximum stimulatory response) = 423 ± 220 nmol/l/h; ACTH: Emax = 1205 ± 481 nmol/l/h). Peak cortisol secretion to these agonists was observed on day 3 (48 h) of cell culture. Cells were also responsive to the pyrimidine nucleotide, UTP. EC50 values for ATP, ADP and UTP were 5.83 ± 3.98 x 10-6 M, 13.7 ± 5.67 x 10-6 M and 7.33 ± 4.52 x 10-7 M respectively. In the absence of specific P2 purinergic receptor antagonists, the receptor subtype(s) mediating the steroidogenic responses to the purines were characterised using selective agonists and second messenger studies. The potency order of a range of purine analogues was as follows: ATP = UTP > ADP > 2-methylthio ATP > α, β-methylene ATP = β, γ-methylene ATP > AMP. ATP, ADP and UTP all dose-dependently stimulated the accumulation of total [3H]-labelled phosphoinositols from cells whose phosphoinositides had been pre-labelled with 3H-inositol. Examination of the purinergic response in bovine zfr cells demonstrated that it fulfils the criteria presently used to define the P2u (nucleotide) receptor. The possibility that cortisol secretion to ATP might be accounted for by the degradation of ATP to adenosine over the course of the incubation was excluded. Although there was degradation, largely to ADP (30%) and AMP (20%), there was no significant formation of adenosine after 1h.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available