Untreated compared to treated OSA is associated with marked disturbances in ACTH and cortisol secretory dynamics, resulting in prolonged tissue exposure to disordered, elevated hormone levels.

A complex dynamic ultradian rhythm underlies the hypothalamic-pituitary-adrenal (HPA) circadian rhythm. We have investigated in normal human male subjects the importance, site of action, and receptor-mediated processes involved in rapid basal corticosteroid feedback and its interaction with corticotrophin releasing hormone (CRH) drive. Pro-opiomelanocortin (POMC), ACTH, and cortisol were measured every 10 min from healthy males during the awakening period or late afternoon using an automated blood sampling system. Mathematical modeling into discrete pulses of activity revealed that intravenous infusion of the synthetic mixed glucocorticoid/ mineralocorticoid agonist prednisolone produced rapid inhibition of ACTH and cortisol pulsatility within 30 min in the morning and afternoon. Any pulse that had commenced at the time of injection was unaffected, and subsequent pulsatility was inhibited. Prednisolone also inhibited ACTH and cortisol secretion in response to exogenous CRH stimulation, inferring rapid feedback inhibition at the anterior pituitary. Circulating POMC peptide concentrations were unaffected, suggesting that the rapid corticosteroid inhibitory effect specifically targeted ACTH secretion from pituitary corticotrophs. Prednisolone fast feedback was only reduced by glucocorticoid receptor antagonist pretreatment and not by mineralocorticoid receptor antagonism, suggesting a glucocorticoid receptor-mediated pathway. The intravenous prednisolone suppression test provides a powerful new tool to investigate HPA abnormalities underlying metabolic and psychiatric disease states.

Apelin is a peptide hormone with cardiovascular and glucose homeostasis properties, and obstructive sleep apnea (OSA) is complicated by cardiovascular and metabolic comorbidities. Plasma apelin has not been previously assessed in OSA. We investigated the response of plasma apelin to a 2-h 75 g oral glucose tolerance test (OGTT) and the effect of 3 months compliant continuous positive airway pressure (CPAP) therapy in 15 obese males with newly diagnosed OSA. Plasma apelin and serum cortisol were recorded 10 minutely, while serum insulin and glucose were measured 30 minutely. Ten subjects had plasma apelin measured at intervals across a 24-h period to investigate for circadian variation in apelin levels, and this was repeated following 3 months compliant CPAP therapy. Fasting (0 . 342G0 . 038 vs 0 . 288 G0 . 024 ng/ml, PZ0 . 04), 30 min (0 . 399G0 . 035 vs 0 . 312 G0 . 036 ng/ml, PZ0 . 007) and 120 min (0 . 402G0 . 030 vs 0 . 259G0 . 024 ng/ml, P!0 . 001) apelin levels were reduced following CPAP. The area under curve for apelin OGTT response was lower post-CPAP (44 . 1G3 . 3 vs 35 . 8 G2 . 3 ng/ml per min, P!0 . 001). Mean OGTT apelin levels showed a significant treatment effect (PZ0 . 006) and a time effect (P!0 . 001), and the effect of time was different preversus post-CPAP (PZ0 . 005). No significant variability in apelin levels existed across the 24-h period at diagnosis. Lower levels were evident overnight following treatment (PZ0 . 004). Improvements in insulin and glucose parameters and reduced cortisol levels were found post-CPAP. In summary, untreated OSA was associated with elevated plasma apelin levels, altered apelin secretory dynamics in response to oral glucose and lack of an apparent circadian variability, which was restored following CPAP.

The serum cortisol response to intravenous synthetic ACTH (tetracosactrin) was assessed in 15 healthy adult cats. Mean cortisol levels showed a significant (P<0.001) rise at 60 minutes and peaked at 180 minutes. At 120 and 180 min‐ utes mean cortisol levels were significantly (P<0.001) higher than at 60 minutes. The time of peak cortisol response in individual cats varied between 120 and 240 minutes, but nine (60 per cent) peaked at 180 minutes. In response to the ACTH the cats showed a rise in cortisol levels of between 160 and 1360 per cent. No significant rise in cortisol levels was seen in five cats following administration of sterile saline.

1. ISA Brown pullets were transferred from 8 to 14 h or from 14 to 8 h photoperiods at 35 or 56 d of age. Controls were maintained on constant 8 or 14 h photoperiods from day 1. 2. Blood samples were obtained immediately before each daylength change and subsequently at 7 d intervals until 1st egg in the treated groups and at 70 d of age and then at 14 d intervals until 1st egg in the constant photoperiod controls. Plasma luteinising hormone (LH) and follicle stimulating hormone (FSH) concentrations were determined using homologous radioimmunoassays. 3. Prior to 16 weeks, LH was consistently higher in birds on constant 14 h photoperiods than in those on constant 8 h, but was down-regulated as birds approached maturity so that LH concentrations in the 2 groups were similar during the final 10 d before the first egg was laid. FISH concentrations rose steadily with age but with a tendency for concentrations to be higher in the 8 h than in the 14 h treatment. Birds on constant 8 h daylengths matured 18.3 d later than those on constant 14 h photoperiods. 4. A 6 h increment in photoperiod given at 35 d or 56 d, resulted in an increase in LH within 7 d in both cases. FSH concentration did not respond to an increase in photoperiod at 35 d but rose following the same increase at 56 d. This was associated with a 3-week advance in sexual maturity, whilst age at 1st egg in birds photostimulated at 35 d was similar to the age with a constant 14 h photoperiod. 5. LH concentration fell when photoperiod was reduced from 14 to 8 h at either 35 or 56 d and remained below the constant 8 h controls for many weeks before rising to a concentration not significantly different from other groups in the final 10 d before 1st egg. FSH concentrations in birds exposed to a decreased daylength at 35 d, although more oscillatory, were similar to the constant 8 h photoperiod controls. In birds exposed to the same decrease at 56 d, FSH concentration initially tumbled but was similar in the 2 groups during the latter stages of rearing; neither differed significantly from the constant daylength controls during the 60 d before 1st egg. Sexual maturity in both groups given a reduction in photoperiod was delayed by about 2 weeks compared with constant 8 h controls. 6. Change in FSH concentration following an increase in daylength was a better predictor of age at 1st egg than change in LH. However, FSH concentrations after 14 weeks of age were rather similar in short day and long day controls and in the 2 groups given reductions in photoperiod at 35 d and 56 d, despite differences of nearly 5 weeks in mean age at 1st egg amongst these 4 treatments.