The Growth Hormone-Releasing Hormone-Cyclic Adenosine-3’,5’-Monophosphate Signal Pathway in Somatotropes Is Practically Intact during Aging

Abstract

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.

Effect of Somatostatin-28 on Growth Hormone Response to Growth Hormone-Releasing Hormone - Impact of Aging and Lifelong Dietary Restriction

“…increases with aging. Age, however, did not sig nificantly influence the responsiveness to GHRH, con firming our recent findings in male rats [1]. Using a simi lar RHPA in female Wistar/Tw rats, Takahashi [19], how ever, reported an age-related reduction in the sensitivity of pituitary cells to GHRH for GH release.…”

“…Furthermore. GHRH-receptor and the subsequent cyclic adenosine-3',5'-monophosphate signal transduction pathway, a major stimulatory pathway for GH secretion, remain virtually intact in indi vidual GH-secreting cells in elderly male F344 rats [1], However, the release of GH from the pituitary gland is competitively regulated by GHRH and somatostatin (SS) [6], In fact, the results of several studies suggest that the increased inhibitory tone of SS may be associated with a diminished secretion ofG H in aging animals [7][8][9][10], Two bioactive forms of SS are present in the hypothal amus, SS-14 and SS-28. The latter is a 14-amino acid Nterminal extension ofSS-14 [11], Sonntag et al [9] dem onstrated in an in vitro study that SS-28, which is more potent than SS-14 in inhibiting GH release from the pitu itary gland [11], is secreted from the hypothalamus in larger amounts in old rats compared with young rats.…”