The growth hormone-releasing hormone-cyclic adenosine-3',5'-monophosphate signal pathway in somatotropes is...

To elucidate the mechanisms of the impaired pituitary response to growth hormone-releasing hormone (GHRH) in aged animals on a cellular basis, a reverse hemolytic plaque assay was performed on dispersed pituitary cells from young (8-month-old) and old (26-month-old) male F344 rats. The proportion of growth hormone (GH)-plaque forming somatotropes, i.e., actually functioning somatotropes, was reduced in old rats to 50-60% of that in young rats under both unstimulated and GHRH-stimulated conditions. The response of dispersed cells to GHRH, however, seemed to remain unchanged with age when expressed as a percent increase of plaque-forming cells from the basal value. The mean diameter of plaques, which reflects the average amount of GH secreted from a single cell, was not smaller in old rats under either the unstimulated or stimulated conditions. There was also no difference between the two age groups in the frequency distribution of the plaque size of functioning somatotropes. The stimulation by forskolin, a compound that directly activates membrane-bound adenylate cyclase and consequently provokes the cyclic adenosine-3',5'-monophosphate (cAMP) pathway for GH secretion in somatotropes, produced almost the same results as those by GHRH stimulation. It was concluded, therefore, that the impaired response of the pituitary gland to GHRH could be due mostly to a reduction in the density of functioning somatotropes rather than to impairments in steps of the GHRH-cAMP signal pathway in somatotropes .