Adrenocortical influences on the development of the diurnal rhythm in hepatic tyrosine transaminase.

Abstract

In the adult rat, liver tyrosine transaminase shows a characteristic diurnal pattern with a peak at 10 PM and a nadir at 10 AM. Infant rats have an inverted pattern with a minimum at 10 PM and a maximum at 10 AM until approximately 21 days of age, when the pattern flattens before changing to the adult form. To determine whether corticoids were essential for the initiation of the adult daily rhythm in liver tyrosine transaminase, rats were adrenalectomized before (16 days of age) and after (21 days of age) the onset of the diurnal variation in circulating corticosterone. Transaminase levels were determined in adulthood. Both groups exhibited the adult rhythm in liver tyrosine transaminase at 55-60 days of age. However, rats adrenalectomized at 16 days of age and sacrificed at 26 days of age still showed the immature rhythm. Drastic alterations of the maternal feeding schedule result in some shift in the infant transaminase cycle. However, adrenalectomized infants maintained with mothers given an ad lib. diet show an abrupt reversal of feeding pattern between day 16-17 and day 22-23 without alteration of the immature rhythm of hepatic tyrosine aminotransferase. The results thus demonstrate that adrenal corticoids are unnecessary for the development of the adult daily cycle although they appear to hasten its maturation into the adult pattern. They further indicate that, although the feeding schedule influences the phasing of the circadian rhythm, it does not wholly account for the inverted rhythm in the infant. (Endocrinology 89 : 936, 1971) S studies (1-3) have reported that diurnal changes in liver tyrosine transaminase in the adult rat persist despite adrenalectomy, although the peak of enzymatic activity is reduced by such endocrinopathy. These data thus indicate that endogenous daily changes in circulating levels of corticoids are unnecessary for the maintenance of the circadian rhythm in tyrosine transaminase in the adult. The development of the rhythms of both adrenal steroids and liver tyrosine transaminase also has been studied. Honova et al. (4) found periodicity in rat hepatic tyrosine transaminase activity as early as 48 hr after birth. Enzyme activity was maximal at 10 AM and minimal at 10 PM. This pattern is inverted from the adult's pattern, where the highest levels of tyrosine transaminase occur at 10 PM. The transition from the immature to the adult cycle occurs between 21 and 23 days of age. The plasma levels of corticosterone do not undergo a diurnal variation in the very young rat (5), but Ader (6) has reported that this rhythm is present at 21-25 days of age. Thus, in Received March 24, 1971. This study was supported by USPHS Research Grant AM 08775. 1 USPHS Postdoctoral Fellow (2-F-2-AM-31,47702), 1968. the rat at least, the circadian rhythm in plasma corticosterone develops either before or simultaneously with the adult daily variation in liver tyrosine transaminase. The possibility existed that, while adrenal hormones were not necessary for the maintenance of the tyrosine transaminase rhy tlim, they may be necessary for the development of the transaminase rhythm or for its normal maturation to the adult form. It has also been demonstrated that the feeding pattern influences tyrosine aminotransferase activity and this may account for the inverted form of the infant rhythm in that infants may feed during periods between maternal feedings (4). Further, adrenalectomy might also alter the feeding pattern and thereby account for the attenuated rhythm in the adrenalectomized adult. Thus, in the adult, an ad lib. diet is accompanied by liver tyrosine transaminase levels which fall to a nadir in the morning, rise in the late afternoon, and peak about 4 hr after the onset of darkness (2). If food consumption is restricted to the morning hours, the peak in hepatic enzyme activity advances to 11 AM (7). The daily rhythm is abolished if the diet lacks protein or is deficient in the amino acid tryptophan (8), and is markedly attenuated if the total daily food intake is dispersed equally throughout the day