Studies on factors which influence cyclic 3', 5'- adenosine monophosphate production in-vivo and in-vitro

Daily variations in plasma (PcAMP), urine (UcAMP), nephrogenous cAMP (NcAMP) and hormones known to affect cAMP metabolism were studied. Circadian variations in PTH (1-84) and NcAMP were observed. Both increased significantly overnight and early morning. PcAMP and glucagon decreased overnight and following meals. PcAMP had greater fluctuations over 24h than glucagon indicating several hormones have transient effects on PcAMP production. A 7h shift of the sleep-wake cycle moved sleep-associated prolactin secretion but caused minimal alteration in PTH (1-84). NcAMP secretion overnight decreased, suggesting PTH (1-84) end organ responses may be modified by other hormones and effectors when sleep is disturbed. PcAMP decreased overnight reaching a nadir corresponding to the lowest glucagon concentration. PcAMP fluctuations were greater when compared to normal 24h profiles. Following a 96h fast serum phosphate, PTH (1-84) and NcAMP circadian rhythms were attenuated. Mean serum calcium and NcAMP production were significantly decreased. Fasting increased variability in PTH (1-84) secretion which may be an important signalling mechanism inducing bone resorption. Serum phosphate fluctuations may play an important role in the genesis of PTH (1-84) and NcAMP circadian rhythms. Mean glucagon concentration was increased with attenuation of the circadian rhythm and mean PcAMP concentration increased. Dissociation of bone and kidney effects of PTH (1-84) in fasting may be due to acute acidosis. In 1°HPT the concerted overnight increase in PTH (1-84) and NcAMP was absent. Parathyroid adenoma resection restored phosphate, PTH (1-84) and NcAMP circadian rhythms. The phosphate increase may stimulate PTH (1-84) secretion which then influences the phosphate rhythm. Mean PcAMP was increased in 1°HPT but 24h PcAMP profiles differed little pre and post surgery. 24h studies indicate control of the circadian rhythms of PTH (1-84), NcAMP and PcAMP is complex. Several hormones act in concert to regulate cAMP generation and end organ responses. Thyrotoxic patients had mean PTH (1-84) and NcAMP lower than normals, hypothyroid and treated hypothyroid patients. Increased serum calcium decreases PTH (1-84) and subsequently NcAMP in thyrotoxicosis. In hypothyroid patients PTH (1-84) and NcAMP are dissociated with mean PTH (1-84) increased compared to thyrotoxic patients but NcAMP remained similar to euthyroid subjects indicating resistance to PTH (1-84) . Thyroxine treated patients have mean PTH (1-84) concentrations lower than euthyroid controls with a relatively increased NcAMP. PcAMP is increased in thyrotoxic and thyroxine treated patients and decreased in hypothyroid patients. Synacthen increased PcAMP with the pattern similar to the cortisol profile. This was either due to simultaneous release of cAMP and cortisol following adrenal stimulation or was a direct effect of cortisol. Dexamethasone decreased NcAMP and UcAMP with a variable effect on PcAMP. Variability in the PcAMP response is probably due to combined effects of dexamethasone and cortisol whereas decreased UcAMP and NcAMP production may represent altered kidney cell sensitivity to PTH (1-84) caused by decreased cortisol. In 1°HPT patients a significant correlation between PTH (1-84) and NcAMP exists (r=0.66, p