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Effects of Adrenocorticotropic Hormone and Growth Hormone on the Metabolism of N-Hydroxy-N-2-fluorenylacetamide and on Physiologic Parameters

National Cancer Institute, Bethesda, Maryland

The effects of large doses of adrenocorticotropic hormone (ACTH) and of growth hormone on physiologic parameters and on the metabolism of N-hydroxy-N-2-fluorenylacetamide (N-OH-FAA) were investigated in Fischer male rats. ACTH, 96 or 80 units, and growth hormone, 12 or 10 mg, were injected s.c. daily for 10 consecutive days into animals prefed either control diet or the N-OH-FAA-containing diet (160 ppm) for 4 weeks prior to the hormonal treatment. ACTH, but not growth hormone treatment, led to increased rectal temperature and body weight loss. Water intake and urine output were elevated by either hormone. ACTH injections enlarged the adrenals 6- to 7-fold and practically involuted the thymus. ACTH caused a significant percentile weight increase in the liver, kidney, heart, and pituitary, but growth hormone did not.

¹⁴C-labeled N-OH-FAA was given on the last day of the hormonal treatment. Urinary excretion of total metabolites, of glucosiduronic acids, and particularly of the glucuronide of N-OH-FAA was increased by both hormones and was especially notable in the carcinogen-prefed animals. These changes suggest that ACTH and growth hormone decreased dehydroxylation and deacetylation of N-OH-FAA. The radioactivity bound to liver proteins was increased, remarkably so in the animals treated with growth hormone.

The results indicate that ACTH plays a paramount role in inducing marked physiologic and metabolic changes, eventually leading to the enhancement of hepatoma formation, as seen in animals fed carcinogen and implanted with MtT, a functional pituitary tumor. The contributing role of growth hormone, however, should not be neglected.

¹ Visiting Scientist, NIH, on leave of absence from the Institute of Physical and Chemical Research, Tokyo, Japan.

Received 5/ 4/66. Accepted 7/21/66.