Fall in Hepatic Cytosol Glucocorticoid Receptor Induced by Stress and Partial Hepatectomy: Evidence for Separate Mechanisms*

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Abstract
An exchange assay has been used to investigate the influence of surgical stress and partial hepatectomy on total (occupied plus unoccupied) hepatic cytosol glucocorticoid receptor concentration in intact and adrenalectomized rats. In animals with intact adrenal glands, cytosol receptor concentration falls by 45% within 6 h of simple laparotomy (sham operation), and by 70% in regenerating hepatic remnants in the same 6-h period after partial hepatectomy. At 24 h, receptor concentration in both sham-operated and regenerating liver begins to rise and, at 72 h (by which time hepatic regeneration is complete), is again at the control, level. In marked contrast to these observations in animals with intact adrenals, sham hepatectomy produces no fall in glucocorticoid receptor concentration in adrenalectomized rats, while partial hepatectomy in these latter animals, deprived of circulating corticosterone, is still followed by a significant loss of receptor. It is concluded 1) that stress can induce a fall in glucocorticoid receptor concentration in rat liver cytosol, 2) that this effect depends upon the presence of the adrenal gland, and 3) that partial hepatectomy also induces a fall in receptor concentration but does so by a mechanism that is independent of adrenal function. The fall in receptor concentration in intact shamoperated animals is consonant with a migration of receptors from cytosol to nucleus secondary to the observed increase in plasma corticosterone and demonstrates that even physiological fluctuations in glucocorticoid levels are capable of inducing marked changes in cytosol receptor concentration in normal liver. In contrast, the data on regenerating liver in both intact and adrenalectomized animals clearly demonstrate a mechanism for the depression of glucocorticoid receptor which functions in the absence of adrenal secretion. This latter mechanism remains to be clarified.