The present study was conducted in order to characterize the secretory pattern of GH in the Shiba goat, a native Japanese miniature goat, and to examine the effects of castration and KP102, a GH secretagogue, on this pattern. Blood samples were taken from an indwelling jugular catheter every 15 min for 24 h, and plasma GH was measured by radioimmunoassay. In intact males, GH was secreted in a pulsatile manner with very regular 5-h periodicity, which consisted of a distinctive GH pulse and a trough of virtually no GH secretion. Postpubertal castration increased the height and decreased the width of GH pulses, though it did not affect the interpulse interval and area under the curve. Modification of the shape of each GH pulse by testicular androgen might play a role in the expression of GH action in the male. KP102 (10 microg/kg, i.v.) immediately induced a robust GH pulse, which was followed by a spontaneous GH pulse of normal characteristics at regular intervals, suggesting that the clock generating GH pulses was reset by KP102. From these observations, we concluded that the Shiba goat is a very suitable experimental model for elucidating the mechanisms underlying GH pulse generation, and in particular, the involvement of androgen and GH secretagogues.

No abstract

ABSTRACT. Growth hormone (GH) is secreted in a pulsatile manner, but the underlying mechanisms of GH pulse generation remain to be resolved. In the present study, we investigated the relationship between GH pulses in the peripheral circulation and GH-releasing hormone (GHRH) and somatostatin (SRIF) profiles in the cerebrospinal fluid (CSF) of male goats. The effects of an intracerebrovent ricular (icv) injection of neuropeptide Y (NPY), galanin and ghrelin were also analyzed. Blood and CSF samples were collected every 15 min for 8 hr from the jugular vein and third ventricle, respectively. GH pulsatility in the goat was found to consist of distinct large pulses of 5 hr periodicity and small pulses of 1 hr periodicity. GHRH and SRIF in the CSF fluctuated in a pulsatile manner with 1 hr periodicity, and most of the descending phase of SRIF pulses were associated with the initiation of GH pulses. Icv injections of NPY, galanin and ghrelin stimulated GHRH release without affecting SRIF release. In addition, NPY suppressed, and galanin and ghrelin induced large GH pulses, although ghrelin was much more effective than galanin. These results suggest that an hourly fall in SRIF is involved in generating intrinsic circhoral rhythm of GH pulsatility. The mechanisms underlying the generation of large GH pulses of 5 hr periodicity remain unknown, while direct action of NPY and/or ghrelin on the pituitary might be involved. KEY WORDS: ghrelin, growth hormone, growth hormone-releasing hormone, NPY, somatostatin.J. Vet. Med. Sci. 66(9): 1071-1078, 2004 Growth hormone (GH) is secreted in a pulsatile manner in all mammalian species studied to date, and this pulsatility plays an important role in the regulation of somatic growth and metabolism [7,10,15,20]. Knowledge of the exact mechanisms underlying the generation of GH pulses is, therefore, of physiological and pathophysiological importance. It is generally accepted that GH pulses are governed by two hypothalamic peptides, GH-releasing hormone (GHRH) and somatostatin (SRIF), which are stimulatory and inhibitory for GH secretion, respectively [15,29,34,41]. Most studies on the neuroendocrine regulation of GH pulsatility have been performed in male rats, in which GH secretion is characterized by a strikingly regular ultradian rhythm with large secretory bursts of every 3-4 hr [15,41]. In the rat, indirect studies such as passive immunizations against GHRH and SRIF suggested that GH pulses depend on GHRH discharge in combination with a decrease in SRIF secretion [29,41]. However, the secretory profiles of GHRH and SRIF under physiological conditions in this species remain to be elucidated because of the technical difficulties involved in collecting pituitary portal blood from unanesthetized animals. On the other hand, direct measurement of GHRH and SRIF in the portal blood from conscious animals has been reported in the sheep [4,12,44]. According to these studies, GH pulsatility in the sheep seemed less regular and the secretory patterns of GHRH and SRIF seemed more complex than ...