Growth Hormone (GH) but not IGF-I-Secretion is Stimulated in Aged Rats by Chronic Hexarelin and GHRP-6 administration

The present studies were designed to investigate in aged rats (22-24 months old) the effectiveness and specificity of acute hexarelin (HEXA) administration on the release of growth hormone (GH), the minimal dose of the peptide that produces the maximal GH secretion and the effects of long term treatment with HEXA or growth hormone releasing peptide (GHRP-6) on plasma levels of GH and IGF-1. To select the appropriate anesthetic to obtain serial blood samples, the GH releasing activity of HEXA (30 µg/kg i.v.) was tested in young rats anesthetized with tribromoethanol and ketamine-xylazine, and the results were compared with those obtained from conscious freely moving rats. When compared to the changes found in conscious rats, the GH-response to HEXA was increased by ketamine-xylazine anesthesia, while it was decreased by tribromoethanol. Therefore, all subsequent experiments were performed in conscious freely moving rats. To determine the minimal effective dose of HEXA and GHRP-6 in aged animals, different doses (5, 10, 20, 40, and 80 µg/kg) of either HEXA or GHRP-6 were administered subcutaneously to young and aged rats. It was found that 20 µg/kg bw of HEXA or GHRP-6 was the minimal dose producing the maximal GH response. Plasma PRL and LH determinations in the animals injected with the minimal dose showed that HEXA and GHRP-6 stimulate the GH release specifically. Based on the results obtained in the latter experiments, young and aged rats were chronically treated with s.c. injections of 20 µg/kg twice a day for 15 or 30 days. At the end of the experiments, animals were acutely tested with s.c. injection of the same dose (20 µg/kg). It was found that both young and aged animals released GH in response to the repeated administration of GH releasing peptides after 15 days of treatment. However, after 30 days of treatment plasma GH did not change when young and aged HEXA treated animals were acutely tested with such peptide, but increased significantly in the GHRP-6 treated animals when they were acutely tested with GHRP-6. In response to the long term treatment with the GH-releasing peptides, plasma IGF-I levels increased in young animals when they were acutely tested with the corresponding peptide. However, plasma IGF-I levels in aged rats were not modified by the acute administration of either HEXA or GHRP-6 after 15 or 30 days of treatment. This study showed that: 1. HEXA and GHRP-6 stimulated GH release in aged rats and the magnitude of GH responses was similar to that in young rats; 2. the minimal dose of HEXA and GHRP-6 resulting in maximal GH response was 20 g/kg and such dose of HEXA specifically stimulated GH secretion in aged rats; 3. fifteen but not 30 days treatment of aged rats with such small dose of HEXA resulted in a similar GH response to subsequent stimulation with the same peptide; 4. plasma IGF-I responses to an acute administration of HEXA or GHRP-6 in rats chronically treated with the same peptide vanished with aging.