Early effects of growth hormone on nucleolar and nucleoplasmic RNA synthesis and RNA polymerase activity in normal rat liver

Abstract

RNA was isolated from nucleoli and extranucleolar (nucleoplasmic) fractions of liver nuclei from hypophysectomized and normal rats and the effects of growth hormone were studied on the incorporation of [ 3H 5]orotic acid into these fractions in vivo. 1. 1. The earliest observable effect of growth hormone on liver RNA of normal rats in vivo is a stimulation of 45-S ribosomal-precursor RNA synthesis in the nucleolus, apparent within 30 min and reaching a plateau after 1 h. 2. 2. A smaller transient stimulation of nucleoplasmic RNA synthesis also occurs, apparent 90 min after growth hormone and over by 2.5 h. 3. 3. These changes cannot be accounted for by alterations in the rate of entry of isotope into the liver cells nor in the specific activities of the intracellular or intranuclear nucleotide pools; the former is unchanged while the latter is slightly lowered by growth hormone. 4. 4. The changes in activity of the RNA polymerases of isolated nuclei confirm the early stimulation of nucleolar and nucleoplasmic RNA synthesis and reveal in addition a biphasic response of the nucleolar enzyme which reaches a peak after 1 h, declines but remains significantly elevated at 2 and 3 h and then rises to a new peak at 4 h. The nucleoplasmic enzyme is significantly elevated at 1 h, reaches a peak at 1.5 h and returns to control levels at 3 and 4 h. 5. 5. Hypophysectomy causes a gross depletion of all nucleolar rRNA species; growth hormone reverses this and restores the profile to normal. 6. 6. Processing and maturation of rRNA in the nucleolus is also stimulated by growth hormone, but this is less marked than the stimulation of 45-S RNA synthesis. 7. 7. Nucleolar RNA from normal rat liver contains a complex peak of approx. 36 S which is labelled almost as rapidly as 45-S RNA. This differs from the minor component of similar size in human nucleoli and is probably specific to rodents.