GROWTH-HORMONE INDUCES SOMATOSTATIN AND INSULIN-LIKE GROWTH-FACTOR-I GENE-EXPRESSION IN THE CEREBRAL HEMISPHERES OF AGING RATS

The neuropeptide somatostatin (SS) plays a role as a modulator of cogn itive functions and as a potential tropic factor in the central nervou s system. A reduction in SS levels has been demonstrated in the aging brain and in dementia. In addition, insulin-like growth factor I (IGF- I) acts as a paracrine factor in multiple GH actions and is also found in the cerebral hemispheres, where it exerts neurotropic effects. We used aging rats as an in vivo model of GH deficiency to study the poss ible participation of exogenous GH in the modulation of the cerebral h emispheric SS and IGF-I. Two sets of experiments were carried out. In the first set, the age-related patterns of GH, IGF-I, and SS in the se rum, pituitary, and cerebral hemispheres were established. In the seco nd experimental set, 90-day-old (adult) and 2-yr-old (aging) male rats received recombinant human GH (200 mu g/ sc . day) or vehicle for 7 c onsecutive days. The serum levels of rat GH and IGF-I as well as pitui tary GH messenger RNA decreased in 2-yr-old rats compared with those i n adult rats. After GH treatment, pituitary GH messenger RNA levels de creased markedly in the 90-day-old and 2-yr-old rats. Serum immunoreac tive GH decreased in the adult animals, whereas it remained unaffected in the aging ones, whereas serum IGF-I levels were not altered by GH treatment in either group. Immunoreactive levels and messenger RNA of both SS and IGF-I were low in the cerebral hemispheres of aging rats, but were restored to the levels found in adult rats after GH treatment . As treatment did not induce changes in the serum IGF-I levels, these results provide evidence of a stimulatory action of peripherally admi nistered GH on the regulation of SS and IGF-I genes in the aging rat i n the central nervous system. These data also show a new target action for GH and could provide a molecular basis for the improvement of som e symptoms of GH deficiency that occurs after recombinant human GH tre atment.