Neuroendocrine aging: Its impact on somatotrophic function

Abstract

In this paper, two different aspects of growth hormone neuroregulation during aging were considered. Twenty-month-old male rats had decreased growth hormone-releasing hormone mRNA levels and a slight reduction of somatostatin mRNA levels in the hypothalamus when compared to 8-month-old counterparts. Short-term administration of biosynthetic human growth hormone (125 μg/rat twice daily, i.p.) to 8-month-old rats reduced hypothalamic growth hormone-releasing hormone mRNA and increased somatostatin mRNA levels. In old rats, growth hormone administration did not significantly change growth hormone-releasing hormone and somatostatin gene expression. Six old beagle dogs received short-term administration of growth hormone-releasing hormone alone or co-administered with clonidine, an α 2-adrenoceptor agonist, and the growth hormone secretory pattern was evaluated during a 6 h period by cluster analysis. In dogs given growth hormone-releasing hormone alone twice daily for 10 days, none of the GH secretory indices were modified except for the increase in the mean GH peak amplitude. By contrast, simultaneous administration of growth hormone-releasing hormone and clonidine, both given twice daily, significantly increased GH peak frequency and total peak area. Administration of clonidine (once daily) associated with growth hormone-releasing hormone (twice daily) further increased the GH secretory indices. In all, the data demonstrate that: (1) the feedback effects exerted by circulating growth hormone on growth hormone-releasing hormone and somatostatin neurons, while evident in adult rats, are not detectable in aged rats; (2) both a hypothalamic component (acted upon by clonidine) and a pituitary component (acted upon by growth hormone-releasing hormone) play a role in the defective growth hormone secretion in old dogs; (3) growth hormone hypofunction is not an irreversible event, since GH secretion may be restored by pharmacological means acting at both the pituitary and the hypothalamic level; (4) clonidine given only once daily is more effective than clonidine given twice daily, perhaps due to the property of this drug to down regulate hypothalamic α 2-adrenoceptors at high doses.