Hormonal Factors Altering Rhythmicity of Tyrosine-alphaketoglutarate Transaminase in Rat Liver1

Abstract

The activity of a hepatic enzyme, tyrosine transaminase (TT), was shown to vary with a 24-hr. rhythm controlled by at least 3 endocrine glands. This enzyme, known to be induced by glucocorticoids or by long-term thyroxine treatment, was measured in male rats at 2- or 4-hr, intervals with a 12-hr.3 day-night lighting. A base line enzyme activity of 3.32-4.20x10-3 U/mg protein was seen in the intact animals between 0800 and 1600. Activity then rose rapidly to reach a single sharp peak at 2200 hr that was 4-5 times greater than base line. Alterations in this pattern were noted following adrenalec-tomy, thyroidectomy, or hypophysectomy. In the adrenalectomized animals the rise at 1600 and peak at 2200 hr. seen in the intact animal were absent, but enzyme activity at 2400 and 0400 hr. was unchanged from normal. Following thyroidectomy enzyme activity rose at 1600 hr., reaching a peak at 2200 that was significantly higher than in the intact animal (p<.01). Activity then fell at 2400 to concentrations not significantly different from the normal base line. These data support the concept of an action of both the adrenal and the thyroid glands in maintenance of normal TT rhythmicity. While a stimulatory effect of each gland contributed to the normal enzyme rhythm, the exaggerated 2200 hr. peak after thyroidectomy suggested that endogenous thyroid hormones in intact animals may modulate the adrenal stimulation of hepatic TT. Following hypophysectomy TT activity at all time periods was significantly depressed. Enzyme activity did not change between 2400 and 1200 hr. A slight elevation from 3.26x10-3 u at 1600 to 5.52x10-3 U at 2200 was followed by a depression to 1.96x10-3 U/mg protein at 2400. Neither corticosterone nor thyroxine given in daily physiologic replacement doses produced normal rhythmicity in hypophysectomized animals. Excessive doses of corticosterone produced a 2-fold rise in TT activity at 1000 and 2200 hr. in intact animals, while large doses of thyroxine had no effect. Thus, pituitary hormones may have influenced TT directly or by mechanism that did not specifically involve target endocrine gland stimulation of hepatic TT. A nocturnal depression of hepatic tyrosine concentrations was unrelated to TT activity and was unaffected by thyroidectomy, adrenalectomy, or hypophysectomy. Possible mechanisms of the observed hormonal interrelationships to the rhythmicity of hepatic TT are discussed.