Age-related changes in GH secretion were studied in the dog. In preliminary experiments, administration of GH-relasing hormone (GHRH-40, 2 \g=m\g/kg,iv) or the \g=a\2-adrenoceptor agonist clonidine (4 \g=m\g/kg,iv) elicited significantly higher plasma GH rises in 3 to 4 years old than in 10 to 14 years old beagle dogs. The pulsatile patterns of GH secretion in both young and old dogs under baseline conditions and after prolonged fasting or clonidine administration were studied. Samples were taken every 10 min from 09.00 to 15.00 h from five young and five old dogs of both sexes. Under baseline conditions, GH peak frequency, total peak area, and integrated GH secretion were significantly lower in old than in young dogs. In old dogs, 5-day complete fasting or 14\ x=r eq-\ day clonidine administration (75 \g=m\g/dog,po, twice daily) increased the frequency and amplitude of spontaneous GH bursts, the total peak area, and the integrated GH secretion. After either stimulus, the GH secretory pattern was quantitatively and qualitatively indistinguishable from that of young dogs under baseline conditions. Similarly, the foregoing indices were significantly increased in young dogs by either stimulus, except for the inability of clonidine to affect peak frequency. These data demonstrate that the defective GH secretion in old dogs is not irreversible, since it is normalized when old dogs are exposed to central nervous system-directed stimuli.Among the several causes proposed for the geria¬ tric changes in structure and function, one is cessa¬ tion of endogenous growth hormone secretion, which occurs in about half of the elderly popula¬ tion (1). There are some similarities between the al¬ terations in ageing and those that occur in GHdeficient patients. In both, there are shrinkage of lean body mass, expansion of adipose mass, dim¬ inution of renal function, and decreased rates of cell division (1). In addition, both kinds of subjects have reduced bone mass and density, dental defi¬ cits, and a decrease in calcium absorption. Consist¬ ent with this proposition, one third of a large group of old subjects (55-80 years) had very low levels of somatomedin-C (2), the GH-related peptide that mediates most of the biological effects of GH (3).If defective GH secretion is one of the pacema¬ kers of ageing, it is of interest to study the mechan¬ isms underlying reduced GH secretion in aged hu¬ mans and animals (2,4-6), with the ultimate goal being to develop suitable pharmacological means for counteracting the age-related phenomena. The present studies were performed in the dog, a species with many aspects of GH regulation resem¬ bling those in humans (7,8).After an initial assessment of the ability of old and young dogs to respond to acute challenges with GH-releasing hormone (GHRH) or clonidine, an a-adrenergic agonist (9), dogs were fasted for a long period or given clonidine, two known stimuli for GH secretion in this species (10)(11)(12), and the ability of these stimuli to alter the secretory pat¬ tern of GH was evaluated over a...

No abstract

It is known that in adult rats, GH by itself and by promoting secretion of the somatomedins acts at the level of the hypothalamus to trigger release of somatostatin and decrease output of GH-releasing hormone (GHRH), thereby inhibiting further secretion of GH. To assess whether these mechanisms are already operative in the early postnatal period, we have evaluated the effect of short-term administration of GH in 10-day-old rats. Twice-daily s.c. administration of 25 micrograms human GH/rat, from days 5 to 9 of life, significantly reduced pituitary content of GH, decreased hypothalamic levels of GHRH mRNA and abolished the in-vivo GH response to a challenge dose of GHRH (20 ng/100 g body weight, s.c.). GHRH (20 ng/100 g body weight, twice daily, s.c.) given concomitantly with the GH treatment, completely counteracted the inhibitory effect of the latter on pituitary content of GH and restored to normal the in-vivo GH response to the GHRH challenge. These data indicate that impaired secretion of GHRH is involved in the inhibitory effect elicited by GH treatment in infant rats. However, concomitant involvement of hypothalamic somatostatin as a result of GH treatment cannot be ruled out. In fact, pituitaries from rats pretreated with GH responded in the same manner as pituitaries from control rats to the GHRH challenge in vitro.