Cortisol Is Secreted Episodically by Normal Man

A normal man received cortisol-4-14C at 0200 hr while he was asleep. After 45 min the specific activity (cpm/μg) of the plasma cortisol was measured at frequent intervals by double isotope derivative analysis using carrier addition and recrystallization to constant isotope ratio. Cortisol levels were also measured on separate portions of the same plasma sample by competitive protein binding analysis and by radiochemical techniques using 3H-cortisol to check manipulative loss. A separate comparison of protein binding and radiochemical methods was also made. It was shown that satisfactory agreement was obtained by these methods. It was shown that rises in plasma cortisol were accompanied by drops in cortisol specific activity (cpm/μg). Falls in plasma cortisol level were associated with an unchanged specific activity. The results demonstrated that in the early morning hours during sleep cortisol was secreted in episodic bursts which were separated by intervals during which there was no cortisol secretion whatever. Utilizing the competitive protein binding method the plasma cortisol level was measured in another normal man at 20 min intervals over a 24 hr day. It was shown that cortisol was secreted episodically throughout the sleeping and waking day in 8 periods of activity separated by quiescent periods. In both these men cortisol production rates were measured by isotope dilution analysis using the urinary metabolites tetrahydrocortisol and tetrahydrocortisone. With some reasonable assumptions it was possible to calculate the approximate amount of cortisol secreted during the episodic adrenal activity. Summation of these estimates gave values in excellent agreement with the measured production rate. Approximately half the day's cortisol production is achieved in the early morning hours during sleep and the secretory episodes are temporally related to rapid eye movement sleep although the relationship is not episode for episode. There was no evidence for steady-state conditions in cortisol level in any portion of the sleep-wake day. It was estimated that the adrenals were secreting at most only 6 hr in a day and were quiescent for the remaining 18 hr. The relationship of these events to a program by the central nervous system is discussed.