ALTERATIONS MOLECULAR SYSTEM GH / IGF-I IN AGING. MECHANISM HIPOTÁLAMO-HIPOFISARIOS AND THEIR REVERSIBILITY.Author:
FERNÁNDEZ MÉNDEZ CAROLINA.
Year:
2004.
University:
COMPLUTENSE DE MADRID [
www.ucm.es].
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: HOSPITAL CARLOS III.
Summary: The rate of secretion of growth hormone (GH) decreases with aging both in humans and in rats, implying a decrease in plasma levels of growth factor similar to the insulin I (IGF-I). The rate of secretion of GH is physiologically regulated by. Neuroendocrine opposite action of at least two hypothalamic neuropeptides, GHRHy SS. GHRH stimulates gene expression and secretion of GH, while SS inhibits its secretion. Also, it has been described that ghrelina, a potent peptide acetylated synthesized in the stomach; hypothalamus and anterior pituitary gland induces secretion of GH through a new mechanism hipotálamo-hipofisario. In this work we analyzed the changes in hypothalamic these factors and their relationship to the alteration of GH on aging, to establish the sequence of events leading to the decline of the synthesis and release of GH happens with age, and study the reversibility of these changes in models in vitro and in vivo. We have demonstrated that aging, like other phases of development, regulates physiologically tod.oslos system components GH / IGF-I. With the aging of the rat there is a decrease in the expression of the gene GHRH enhipotálamo, less content and release in median eminence, with a primary charge of the event deficit RI happens with age, setting aside an increase in the tone somatostatinérgico as mechanism of the lesser of GH secretion. Furthermore, we have shown that the age produces a decrease in the expression of the receptor in the hypothalamus and pituitary secretagogues, indirectly suggesting the involvement of the GHS and GHRH in these alterations. Also, it was ruled an increase in IGF-I regulation negative exercises at hypothalamic during aging. We have also shown that cells somatotropas rat old in primary culture maintain the same characteristics in that. Alive, and that their ability to respond to stimuli as GHRH yghrelina not changed with age. In this model, the short treatment with GHRH reverses the lower gene expression of Pit-1, and the lesser of GH secretion, and in the model cocultivo we have studied the sensitivity SS, revealing the blockade on the action of GHRH and , secretagogues is not changed with age. In addition, this model treatment short ghrelina, completely reverses the lower GH secretion that occurs during aging. Finally, we demonstrated that chronic treatment with GHRP-6 increased serum levels of GH and reverses the lower concentration of IGF-I in serum that occurs during aging. Place an increase in IGF-I gene expression in liver. In addition,. SS absence of the chronic treatment with secretagogues completely reverses the lower synthesis and secretion of GH happens with age.
