Changes in rat adrenal cyclic nucleotides during normal and neoplastic growth

Stowe, N.W.; Whitley, T.H.; Ney, R.L.; Steiner, A.L.

Biochimica et Biophysica Acta 497(3): 690-701


ISSN/ISBN: 0006-3002
PMID: 196665
DOI: 10.1016/0304-4165(77)90290-2
Accession: 004911234

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In an attempt to correlate changes in cyclic nucleotide levels with in vivo growth of the rat adrenal gland adrenal cyclicAMP and cGMP were measured in normal, hyperplastic and neoplastic rat adrenals. The 1st group of animals were subjected to unilateral adrenalectomy (ADX) or acute hypophysectomy 1 h prior to unilateral adrenalectomy (HADX). Cyclic nucleotides were measured in the contralateral adrenal postoperatively. In HADX rats cGMP rose steadily throughout the 7 day study period, while ADX rats exhibited significant decreases in adrenal cGMP. cAMP remained 1.5 pm/mg tissue in HADX rats, while in ADX rats there was significant elevation of adrenal cAMP at all time points. cGMP/cAMP ratios remained constant in HADX animals. The growing adrenals of ADX animals exhibited depressed cGMP/cAMP ratios at all time periods. Adrenal hyperplasia was induced in a 2nd group of animals by a transplantable ACTH secreting pituitary tumor. Adrenals from age matched animals served as controls. Adrenal cAMP was significantly elevated in tumor-bearers at a time corresponding to the peak accumulation of adrenal weight, protein and DNA in these animals. Adrenal cGMP in tumor-bearers and control animals fell steadily throughout the study period. cGMP/cAMP ratios of control animals decreased 2-3 wk posttransplant, remaining at the 3 wk value during the period corresponding to rapid adrenal growth in tumor-bearers. The cGMP/cAMP ratio in the hyperplastic adrenals of tumor-bearers decreased steadily throughout their rapid growth period, suggesting a positive correlation between adrenal growth and depression of the cGMP/cAMP ratio. Cyclic nucleotide levels in neoplastic adrenals of rats bearing the transplantable adrenocortical carcinoma 494 were compared with cyclic nucleotides in normal rat adrenal glands. cAMP was not different in the 2 groups. The cGMP content of neoplastic adrenals was significantly lower than that of normal adrenal tissue, causing a suppression of the cGMP/cAMP ratio in the neoplastic tissue. Measurement of adrenal cyclic nucleotides in hyperplastic and neoplastic rat adrenal glands suggests that adrenal growth in vivo may be characterized by a depression of the cGMP/cAMP ratio.