Site of fast, rate-sensitive feedback inhibition of adrenocorticotropin secretion during stress.
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Biomedical subjects
Publications and source records attributed to T Hiroshige.
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Three biological rhythms (locomotor activity, body temperature, and plasma corticosterone) were measured simultaneously in individual rats under light-dark cycles and continuous light. Spontaneous locomotor activity was recorded on an Animex and body temperature was telemetrically monitored throughout the experiments. Blood samples were obtained serially at 2-h intervals on the experimental days. Phase angles of these rhythms were calculated by a least-squares spectrum analysis. Under light-dark cycles, the acrophases of locomotor activity, body temperature, and plasma corticosterone were found at 0029, 0106, and 1940 h, respectively. When rats were exposed to 200 lx continuous light, locomotor activity and body temperature showed free-running rhythms with a period of 25.2 h on the average. Plasma corticosterone levels determined at 12 days after exposure to continuous light exhibited a circadian rhythm with the acrophase shifted to 0720. The acrophases of locomotor activity and body temperature, determined simultaneously on the same day, were found to be located at 1303 and 1358 h, respectively. Phase-angle differences among the three rhythms on the 12th day of continuous light were essentially the same with those under the light-dark cycle. These results suggest that circadian rhythms of locomotor activity, body temperature, and plasma corticosterone are most probably coupled to a common internal oscillator in the rat.
Circadian rhythms of locomotor activity, body temperature, and plasma corticosterone were determined simultaneously in individual rats that were exposed to 200 lx continuous light for over 3 mo. Free-running circadian rhythms of locomotor activity persisted for about 2 mo under continuous light and then the rhythms gradually decomposed. After 3 mo of exposure, circadian rhythms disappeared and activity bursts of 1- to 2-h duration manifested themselves several times during a 24-h period. Body temperature also exhibited several bursts of fluctuation and these bursts were closely correlated in their temporal sequence with those of locomotor activity. A least-squares spectrum analysis revealed that the burst had regular 4- to 6-h periods. Plasma corticosterone, determined by serial sampling at 2-h intervals from individual rats, also exhibited several secretion episodes in a day. These episodic secretions synchronized with bursts of locomotor activity. These results suggest that the ultradian component, manifested under prolonged continuous light, is a fundamental unit of the circadian rhythm and an oscillator for the ultradian rhythm is common to the three functions examined.
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Stimultaneous determination of the circadian rhythms of locomotor activity and body temperature was carried out in the rat. Deep body temperature was monitored continuously using a telemetric device. The circadian rhythm of locomotor activity was characterized by clustering of several bursts of activity during the dark period. The circadian rhythm of body temperature was also characterized by bursts of small fluctuations which were well correlated with those of locomotor activity. Correlation between the two functions was such that the regression line expressing body temperature as a function of locomotor activity had approximately the same slope for dark and light periods, but a body temperature for a given amount of locomotor activity was significantly higher during the dark period than during the light one. After a prolonged exposure to constant light, the circadian rhythm disappeared in both functions. Both showed bursts of fluctuations which were correlated with each other. These results indicate that the bursts of body temperature increment were dependent on those of the locomotor activity. However, manifestation of the circadian rhythm per se of body temperature could not be explained as resulting exclusively from the circadian fluctuation of locomotor activity.
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Features of several assays for corticotropin-releasing factor (CRF) were compared, with reference to sensitivity, precision, specificity and convenience. In general, in vivo assays are less specific, whereas in vitro assays with isolated pituitary cells appear to suffer from vulnerability. Promising approaches for overcoming this difficulty are appearing: one is the cell culture technique and the other is the perfusion of pituitary cell column. However, the findings with vasopressin are again discordant. So far, the in vivo-in vitro assay system appears to be the most satisfactory. In this connection, special emphasis was laid on the CRF assay by out intrapituitary injection technique through the parapharyngeal approach, which has features of both in vivo and in vitro systems. The drawbacks with this assay are its complexity and relatively lower precision. Problems of the use of dexamethasone are discussed from a viewpoint of possible multistage feedback inhibition, as postulated by Yates et al. Several findings on the CRF dynamics were mentioned, in order to exemplify the findings obtained with our assay: it was shown that the two-peaked changes of CRF after ether-laparotomy stress in adult rats were composed of heterogeneous components, as revealed by differential effect of cycloheximide. Pretreatment with cycloheximide similarly abolished the delayed CRF peak that was observed in 2-day-old neonatal rats under stress. These findings suggest an operation of a biochemical denominator in common with both cases.
The role of ketone bodies (KB) in nonshivering thermogenesis was investigated in warm- and cold-acclimated rats with and without norepinephrine (NE) loads. NE-induced calorigenesis, as evidenced by changes in rectal temperature, was highly developed in cold-acclimated rats, but the levels of blood KB and free fatty acids (FFA) remained almost unaltered. In contrast, FFA turnover rate in cold-acclimated rats under NE load was much greater than in warm-acclimated rats. Similarly, turnover rate of beta-hydroxybutyrate estimated from decay curves of the endogenous substrate in functionally eviscerated rats was significantly higher in cold- than warm-acclimated rats. Perfused livers from cold-acclimated rats produced more KB than warm-acclimated ones. No significant effect of NE load was observed in either group. Quantitative analysis shows that the turnover rate of KB in vivo essentially equals the production rate in the perfused liver when no exogenous NE is added. In contrast, under constant NE infusion the turnover rate in vivo was almost double that of the perfused liver. These results indicate that KB are an energy source as important as FFA in nonshivering thermogenesis. It may be further surmised that increased KB production in vivo, particularly in the cold-acclimated state, is affected by factor(s) other than NE.
Post-natal development of the circadian rhythm of hypothalamic content of corticotrophin-releasing factor (CRF) was examined in male and female rats, separately. CRF activity was estimated by the intrapituitary injection technique. The circadian rhythm of the CRF content observed at the third week was without any noticeable sex difference: both male and female rats began their circadian rhythm with higher values in the afternoon than in the morning. Male rats maintained this pattern up to maturity. In contrast, female rats showed a marked change at ages of fifth to sixth week: the CRF rhythm in female rats changed to a female pattern, with higher values in the morning than in the afternoon. During this period, the vaginal opening occurred concurrently with a marked afternoon rise in the plasma corticosterone, characteristic of mature female rats. On the other hand, no essential difference could be observed between male and female rats in the developmental change in the circadian rhythm of locomotor activity. These results indicate that a sex difference in the CRF rhythm is not essentially related to the process of sex differentiation in the central nervous system, but is rather related to changes in ovarian activity following the onset of puberty.
In order to know the mode of action of norepinephrine in enhanced utilization of plasma free fatty acids (FFA) in cold acclimation, albumin-bound 14C-palmitate was infused intravenously at a constant rate into cold- and warm-acclimated rats under pentobarbital anesthesia with and without norepinephrine infusion. Rectal temperature, CO2 output and plasma FFA, from which the rates of FFA uptake and oxidation were calculated, were determined simultaneously. Similar fractions, that is, 7 and 5% of the total uptake of plasma FFA by the tissue were immediately oxidized in both cold- and warm-acclimated rats, respectively. Norepinephrine infusion caused a significant increase in all the parameters examined. In addition, during hormone infusion the percentage of FFA uptake oxidized was elevated from 22% in control to 50% in cold-acclimated rats. This increment was accompanied with greater increases in rectal temperature and CO2 output. Similarly, in functionally eviscerated cold-acclimated rats, norepinephrine induced a greater increase in the percentage of FFA uptake oxidized than in eviscerated controls. These results indicate that although the FFA uptake was increased simultaneously norepinephrine infusion casued a more marked acceleration of the oxidation of plasma FFA in the cold-acclimated rats than in control rats.
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