Pituitary alterations involved in the decline of growth hormone gene expression in the pituitary of aging rats.

Growth hormone (GH) declines during aging. This study investigates whether pituitary constitutive alterations may be involved in the GH decline. Two groups of male Wistar rats were studied (young: 3-month-old; old: 24-month-old). The old rats showed lower pituitary GH messenger RNA (mRNA) levels, immunoreactive rat (IR)-GH content, and GH secretion with no difference in pituitary Pit-1 and cAMP-response element-binding protein (CREB) expression. Pituitary GH releasing hormone receptor (GHRH-R), GH secretagogue receptor (GHS-R), sstr2, and sstr5 mRNA levels were significantly reduced in old rats. The percentage of GH immunoreactive cells was similar in both groups. In vitro, pituitary IR-GH response to GHRH, forskolin (FK), ghrelin, and insulin-like growth factor I (IGF-I) was similar when compared with respective basal secretion and somatostatin-diminished GHRH- and ghrelin-induced IR-GH release in both groups. These results indicate that, as somatotrope function is maintained in aging, the changes observed in GH gene expression and secretion could be reversed by GHS.