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Pituitary Alterations Involved in the Decline of Growth Hormone Gene Expression in the Pituitary of Aging Rats

¹ Endocrine Service and ³ Immunology Service, Hospital Carlos III, Madrid, Spain.
² Endocrine Service, Hospital Ramón y Cajal, Madrid, Spain.

Address correspondence to Franco Sánchez-Franco, MD, PhD, Endocrine Service, Hospital Carlos III, C/ Sinesio Delgado, 10, Madrid 28029, Spain. E-mail: sanchezfr{at}terra.es

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.