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Ultradian Rhythm of Basal Corticosterone Release in the Female Rat: Dynamic Interaction with the Response to Acute Stress¹

Neuroendocrine Research Group, Department of Anatomy, University of Bristol School of Medical Sciences (R.J.W., S.A.W., C.D.I.), Bristol, United Kingdom BS8 1TD; and the Department of Medicine, University of Bristol, Bristol Royal Infirmary (R.J.W., S.A.W., N.S., S.L.L.), Bristol, United Kingdom BS2 8HW

Address all correspondence and requests for reprints to: Dr. Richard Windle, Neuroendocrine Research Group, Department of Anatomy, University of Bristol School of Medical Sciences, Bristol, United Kingdom BS8 1TD. E-mail: r.j.windle{at}bris.ac.uk

The present study investigated the dynamic regulation of the hypothalamo-pituitary-adrenal axis and its significance to acute stress responsiveness in the female rat. An automated, frequent blood-sampling technique allowed the circadian rhythm of corticosterone to be resolved into a series of pulses. These were equally distributed (mean interval, 50.9 ± 3.7 min) throughout the 24-h cycle, but their magnitude varied significantly, being higher between 1800–2200 h (137 ± 9 ng/ml) than between 0600–1000 h (75 ± 17 ng/ml). This pattern of release indicates continuous, but variable, activity of the axis throughout the day. The pulsatile ultradian rhythm suggested alternate periods of secretion and inhibition, which were found to have a profound effect on the corticosterone responses to acute stress. Noise stress (10 min, 114 decibels) evoked a transient increase in corticosterone, which reached a maximum (377 ± 87 ng/ml) 20 min after onset. However, within this group (n = 26) the response varied depending on the underlying basal activity. When stress coincided with a rising (secretory) phase of a pulse, corticosterone concentrations rose to 602 ± 150% of mean basal concentrations (P < 0.001). In contrast, when stress coincided with a falling (nonsecretory) phase of a pulse, a significantly smaller response, no greater than a basal pulse, was evoked. Thus, the alternate periods of secretion and inhibition generating basal hypothalamo-pituitary-adrenal activity are an important determinant of responses to acute stress.

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