Sixteen Weeks of Hexarelin Therapy in Aged Dogs: Effects on the Somatotropic Axis, Muscle Morphology, and Bone Metabolism

Hexarelin (HEXA; 500 \hg/kg/die, s.c.) was administered for 16 weeks to six old beagle dogs. The treatment consisted of three on-drug periods spaced by two off-drug periods. During each on period, the growth hormone (GH) peak response to HEXA initially increased and then dropped to pretreatment values. Each time, a wash-out interval restored the same pattern ofGH responsiveness. HEXA significantly augmented the indices of spontaneous pulsatUity ofGH, but plasma insulin-like growth factor I levels did not change during treatment. HEXA apparently reduced bone resorption since it significantly decreased the urinary concentration of lysylpyridinoline, a bone matrix component. Bone formation apparently was not offected since unchanged levels of alkaline phosphatase were recorded. In three of six old dogs, HEXA induced an improvement of some morphological and biochemical muscular indices, evaluated in muscle specimens that, instead, remained unchanged in a group of young untreated controls. These findings indicate that HEXA effectively releases GH and primes the pituitary of old dogs, and strengthen the view that in aging, GH secretion may be restored by pharmacological means. It would also appear that HEXA-induced GH release improves some indices of body composition in old dogs. A REDUCED function of the somatotropic axis is a char-•** • acteristic feature of normal aging. In most individuals of different animal species and humans, circulating concen