Intraventricular administration of nerve growth factor induces ornithine decarboxylase in peripheral tissues of the rat.

Intraventricular administration of nerve growth factor causes an increase in the activity of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) in liver, kidney, and adrenal as well as in brain itself. An increase in the concentration of corticosterone in the blood was also observed. Adrenalectomy, hypophysectomy, or pituitary stalk section inhibits the increase of ornithine decarboxylase activity in the peripheral tissues. Ornithine decarboxylase activity in the brain, however, responds to nerve growth factor in these animals. The data indicate that nerve growth factor causes an acitivation of the hypothalamo-hypophyseal endocrine system.

Nerve growth factor increases activity of ornithine decarboxylase in rat brain.

Intraventricular administration of nanogram quantities of nerve growth factor to adult rats results in a marked increase in the activity of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) in the brain. The increase occurs in all major brain regions and the activity is maximal by 7.5 hr after administration. The enzyme response to nerve growth factor increases in magnitude during maturation; the relative increase in ornithine decarboxylase activity in adult animals is much greater than that in young. Neither insulin nor bovine growth hormone was able to increase ornithine decarboxylase activity to the same extent as did nerve growth factor. When brain was separated into neuronal- and glial-enriched fractions, induction of ornithine decarboxylase was found in both, but a greater increase was observed in the glial fraction.

Nerve growth factor increases activity of ornithine decarboxylase in superior cervical ganglia of young rats.

Nerve growth factor produces a rapid increase in the activity of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) in superior cervical ganglia of young rats in vivo and in vitro. Maximum activity occurs 6-7 hr after the addition of nerve growth factor. The nerve growth factor-mediated increase in ornithine decarboxylase activity in vitro can be prevented by the addition of cycloheximide, actinomycin D, or antibody to nerve growth factor. A number of other agents were tested for their ability to increase ornithine decarboxylase were tested for their ability to increase ornithine decarboxylase activity in the ganglia; only nerve growth factor, and, to a slight extent, insulin were able to raise the activity of the enzyme. High concentrations of dibutyryl cyclic AMP (10 mM) were able to mimic the effect of nerve growth factor.

Selective de novo synthesis of tyrosine hydroxylase in organ cultures of rat superior cervical ganglia after in vivo administration of nerve growth factor.

Tyrosine hydroxylase is synthesized de novo in rat superior cervical ganglia in organ culture. The differential rate of synthesis is not increased significantly by the addition of nerve growth factor to the culture. Prior administration of nerve growth factor in vivo, however, leads to an augmented synthesis of tyrosine hydroxylase in ganglia subsequently cultured in vitro. The differential rate of tyrosine hydroxylase synthesis was increased by a factor of between 3 and 4. Increases in the differential rate of synthesis were detected within 6 h; the rate reached a maximum 24 to 36 h after a single injection of nerve growth factor. Administration of actinomycin D or of nerve growth factor antibody in vivo prevented the nerve growth factor-induced increase in the differential rate of tyrosine hydroxylase synthesis in vitro. However, the increase in the synthetic rate of tyrosine hydroxylase was not prevented by the addition of actinomycin D to the culture.