Adrenocorticotropin analogs and glucocorticoids in the hypophysectomized rat. II. Effects on cerebral cortex...

The capacity of free polyribosomes from rat cerebral cortex to incorporate labeled amino acids into protein (polyribosome activity) was compared in normal, hypophysectomized, and treated hypophysectomized rats. Polyribosome activity was measured in a cell-free system using a pH 5 supernatant from sham-operated rats. The polyribosome activity of hypophysectomized rats was 10-20% less than that of sham-operated rats. Subcutaneous treatment of hypophysectomized rats daily for 10 days with ACTH, corticotropic ACTH fragments [10-2- microgram of ACTH-(1-24), ACTH-(1-23), or Hoe 433 (ACTH-(1-17))], or glucocorticoids (1 mg corticosterone or 10 microgram dexamethasone) stimulated activity to a level 25-50% higher than that in sham-operated rats. Polyribosome aggregation, as measured by sucrose density gradient analysis, was also greater in treated hypophysectomized rats than in sham-operated rats. On the other hand, a daily sc dose of 100 microgram of the noncorticotropic fragment, ACTH-(1-10), did not stimulate brain polyribosome activity in hypophysectomized rats but merely restored it to the level observed in sham-operated rats. The present study suggests that stimulation of cerebral protein synthesis by ACTH and corticotropic ACTH analogs may be partly due to their ability to promote adrenal steroid secretion. Their stimulatory effect and that of glucocorticoids might explain their physiological roles during stress and learning.