European Journal of Anatomy

Official Journal of The Spanish Society of Anatomy
Cover Volume 13 - Number 2
Eur J Anat, 13 (2): 83-90 (2009)

Antagonism between Ghrelin / GH secretagogues and somatostatin in arcuate and periventricular nuclei in prepubertal female rats

Garcia-Martinez E., Rojas J.P., Canete Ma.D., Bernai G., Canete R., Jimenez-Reina L.

Departamento de Ciencias Morfológicas, Facultad de Medicina, Universidad de Córdoba, 14004 Córdoba, Spain; Departamento de Pediatría, Unidad de Endocrinología Pediátrica, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain

ABSTRACT Combined growth hormone-releasing hormone (GHRH) and growth hormone secretogogues (GHS) have been used alone or in combination with somatostatin (SRIF) to study the pituitary growth hormone (GH) reserve in adults with GH deficiency, but not in children, owing to the possible adverse effects of these treatments. The study aimed to assess the response of the arcuate and periventricular hypothalamic nuclei, using Fos protein as a marker of neuron activity, and to compare that response with the GH response to different stimuli in the presence or absence of SRIF in prepubertal female rats. Rats received the following intraperitoneal stimuli: GHRH (1?g/kg), GHRP-6 (1 ?g/kg), ghrelin (1 ?g/kg), and GHRH combined with either GHRP-6 or ghrelin, with or without SRIF pretreatment 90 minutes prior to stimulus. The animals were decapitated at different intervals; trunk blood was obtained for the measurement of GH levels using a radioimmunoassay technique, and hypothalamic sections were processed for immunochemical determination of Fos protein expression. In the arcuate nucleus, except for GHRP-6 all stimuli increased Fos protein activity in the absence of SRIF pretreatment; the same effect was achieved by pretreatment with SRIF, although this pretreatment prevented the increase in neuronal activity following all stimuli, except that with GHRH + GHRP-6. In the periventricular nucleus, stimulus with GHRH, GHRP-6, ghrelin and GHRH+ghrelin caused a decline in Fos protein expression in the absence of SRIF, whereas SRIF pretreatment prompted a decrease in Fos protein expression that was counteracted by GHRP6 and GHRH + ghrelin. Peak serum GH values were recorded 15 minutes after the administration of GHRH+ghrelin and GHRH + GHRP-6. SRIH pretreatment inhibited GH release, with a subsequent «escape» and lack of response to stimulation which lasted at least 30 minutes, except following the administration of GHRH. The results suggest that all these actions may be due to functional antagonism between ghrelin/ GH secretagogues and somatostatin.

Keywords: ghrelin, growth hormone, growth hormone releasing factor, growth hormone secretagogue, histidyl dextro tryptophylalanyltryptophyl dextro phenylalanyllysinamide, protein fos, somatostatin, animal experiment, arcuate nucleus, article, drug activity, electroencephalogram, female, hormone blood level, nonhuman, protein expression, rat, thalamus midline nucleus

European Journal of anatomy
ISSN 2340-311X (Online)