Peripheral growth hormone induces cell proliferation in the intact adult rat brain

Growth hormone (GH) and insulin-like growth factor I (IGF-I) increase cell genesis in several regions of the brains of GH-IGF-I-deficient hypophysectomized rats. However, it is not known to what degree GH treatment stimulates adult cell genesis in pituitary-intact rodents. We investigated the effect of peripheral administration of bovine growth hormone (bGH) on cellular proliferation in various regions of the brains of normal adult female rats. To monitor cell division, bromodeoxyuridine (BrdU) was administered daily for 5 days. We studied the two areas of ongoing neurogenesis, the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus, as well as the corpus callosum, striatum, and the parietal and piriform cortices. After bGH treatment, the numbers of BrdU-positive cells increased 2.0- to 2.5-fold in all the brain regions, with the exception of the SVZ, in which there was no increase in the numbers of BrdU-positive cells. The present study shows for the first time that peripheral bGH administration increases the generation of new brain cells in normal adult female rats. Thus, bGH may stimulate cellular proliferation not only under GH-deficiency, but also under physiologic conditions. These findings have important implications for GH treatment strategies for patients who have normal or near-normal circulating levels of GH or IGF-I.