Adrenal Rhythmicity Research Articles

Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.

The normal pattern of daily glucocorticoid production in mammals requires circadian modulation of hypothalamicpituitary-adrenal axis activity. To assess both the factors responsible for imparting this diurnal profile and its physiologic importance, we have exploited corticotropin-releasing hormone (CRH)-deficient mice generated by homologous recombination in embryonic stem cells. CRH-deficient mice have lost normal circadian variations in plasma ACTH and glucocorticoid while maintaining normal circadian locomotor activity. Constant peripheral infusion of CRH produced marked diurnal excursions of plasma glucocorticoid, indicating that CRH acts in part as a permissive factor for other circadian modulators of adrenocortical activity. The presence of atrophic adrenals in CRH-deficient mice without an overt deficit in basal plasma ACTH concentration suggests that the diurnal increase in ACTH is essential to maintain normal adrenal function.

Effect of pituitary graft-induced hyperprolactinemia on adrenal circadian rhythmicity.

Prolactin is involved in the regulation of several endocrine functions. In this study, the possible influence of hyperprolactinemia on circadian corticosterone secretion has been investigated. Pituitary grafted male and female rats exhibited increased plasma PRL levels at 1000 when compared to sham-operated controls. This increase was only maintained over the 24 h period in grafted female rats but not in males, thus suggesting a different sex dependent modification of the regulatory mechanisms of prolactin. The corticosterone secretion pattern in sham operated male and female rats was similar to those described earlier but was altered by hyperprolactinemia according to the sex of the animal. There was a significant decrease in the total amount of corticosterone secreted in a 24 h period in grafted males as compared to control animals, whereas no significant differences were observed in grafted female rats as compared to controls. Grafted females showed a 4 h delay in the 24 h secretion rhythm as compared to control animals. These data suggest that pituitary transplant induced hyperprolactinemia, directly or through modifications in catecholamine turnover, is able to modify adrenal rhythmicity.

Pituitary-Adrenal Function in Rats Chronically Exposed to Cold

Exposure to cold for 2 weeks was used to assess the effects of a sustained stimulus on pituitary-adrenal function in male rats. The diurnal peak in plasma and adrenal corticosterone was advanced by 4 h during the first 24 h of exposure to cold but returned to its usual time (2000 h) by the next day. Plasma ACTH and corticosterone levels were generally greater at all times during the 24-h cycle in animals exposed to cold for up to 2 weeks, with the greatest increase occurring consistently at the time of peak. When rats exposed to cold for 1 week were returned to a normal 24 C environment, plasma corticosterone tended to increase. Plasma ACTH and plasma and adrenal corticosterone responses to a superimposed acute provocative stimulus (ip saline injection) were faster, greater, and more sustained in rats exposed to cold for 3 or 7 days. Similarly, the compensatory adrenal hypertrophy response to unilateral adrenalectomy was greater in cold-exposed rats. Such animals were also more resistant to pituitary-adrenal suppression by prednisolone. In contrast, there was no change in the sensitivity of the adrenal to exogenous ACTH. The results suggest that chronic exposure to cold causes a sustained activation of central mechanisms that regulate pituitary ACTH secretion as well as extra-pituitary mechanisms that regulate adrenal size; it reduces the effectiveness of negative feedback mechanisms, but does not alter those involved in the regulation of adrenal rhythmicity or adrenal sensitivity to ACTH.

Circadian periodicity of plasma corticosterone levels in rats subjected to hemorrhagic shock and surgical trauma.

The effects of surgical trauma and hemorrhagic shock on the circadian rhythmicity of corticosteroid secretion in the rat were investigated. The estimations were performed at 4-hour intervals for a 24-hour period. Control animals exhibited a characteristic circadian rhythm of plasma corticosterone with peak concentrations occurring at 8 p.m. followed by a gradual fall during the night, reaching a minimum at 8 a.m. Severe stress induced by hemorrhagic shock or surgical trauma caused a dramatic alteration in corticosterone rhythms which persisted up to 72 h following surgery or hemorrhage. It is apparent that the physiological mechanisms which regulate adrenal rhythmicity are disrupted for a prolonged period following major stress or trauma.

The role of adrenal rhythmicity in puberty: effects of intermittent steroid replacement.

Tests were done to determine whether sensitive periods exist when corticosterone replacement would be more effective in normalizing puberty in adrenalectomized rats. Rats were adrenalectomized at 22 days of age when adreanlectomy delays puberty or at 28 days of age when it does not. Either saline injections or injections of .5 mg corticosterone were given 3 times daily (8 A.M. 4 P.M. and 11 P.M.) beginning on the day of surgery. Survival rates were low. Corticosterone levels following either the saline injections or the .5 mg of corticosterone remained comparable after a week. Saline injections beginning at 22 days of age when given at 11 P.M. delayed puberty in intact rats but not when given at other times. In sham-operated rats saline given at 8 A.M. delayed puberty but given at other times it did not. Saline injections in adreanlectomized rats delayed puberty longer than the operation alone (p less than .01). Corticosterone replacement produced normal vaginal openings and earlier ovulation than in saline-treated rats but ovulation was delayed beyond that of controls (p less than .01). Corticosterone injections at the 3 different time periods were equally effective. Therefore a daily sensitive period for advancing puberty in adrenalectomized rats by corticosterone injections was not shown. Adrenal rhythm does shift in rats exposed to sham surgery before puberty. Daily injection stress in delaying puberty does depend on the time of injection.

Central nervous system mediation of pituitary adrenal rhythmicity

Evidence favoring the view that there is a dissociation between the two aspects of pituitary adrenal operation, the stress and the rhythm modes, is as follows 1) it is possible to abolish rhythmic function by anterior hypothalamic lesions without altering the responses to stress; 2) during maturation of the rat CNS, the stress response appears prior to weaning while pituitary-adrenal rhythm appears after weaning; 3) appropriate neuropharmacologic treatment can block circadian rhythm without altering the stress response; 4) responsiveness to ether or immobilization may be independent of the diurnal rhythm; 5) the stress response to a very strong stimulus, such as immobilization, habituates while the circadian rhythm does not. On the other hand there is some evidence in favor of interdependence between the two modes of operation: 1) input channels for stress and rhythm may overlap since strong synchronizers of rhythm, such as food and water restriction and light can become stress stimuli; 2) steroid feedback can alter the timing of the circadian rhythm; 3) circadian variation has been observed in the responses to certain stimuli; 4) neurotransmitters which are prominently implicated in the circadian rhythm also appear involved in the stress response.

The effect of an acute light cycle change on adrenal rhythmicity in prepubertal rats.

24 and 28 day old rats, raised in a 14 h light: 10 h dark (14:10) cycle, showed a clear serum corticosterone (B) peak at the beginning of the dark period (18.00 h) with an amplitude of 25-30 mug%. Other B values during the 24 h period were lower (9-12 mug%). Rats raised in a 8.5:15.5 cycle had a B peak (after onset of the dark period, at 22.00 h). Rats raised in constant light (LL) showed no variation in B throughout the 24 h. Weanling rats raised in a 8.5:15.5 cycle appeared to synchronize more rapidly to a 14:10 cycle than did rats raised in LL. When placed in LL at weaning, rats raised either in 14:10 or 8.5:15.5 had lost their periodicity by day 24. When rats raised in 8.5:15.5 were shifted to LL or 14:10 after weaning age (day 24), the pattern of response was different. One day after the shift, rats placed in a 14:10 cycle displayed a pattern of B synchronized to the normal 14:10 pattern for rats born and raised in that light cycle. This synchrony persisted for at least 3 days. Rats placed in 14:10 at 21 days of age did not show a fully synchronized pattern until day 28. It can be concluded that weanling rats exposed to a light-dark cycle adapt quickly to a new light cycle and that older prepubertal rats shift even more quickly.

Eosinophil rhythm in mice: range of occurrence; effects of illumination, feeding, and adrenalectomy.

Eosinophil rhythm in mice: range of occurrence; effects of illumination, feeding, and adrenalectomy.