Abstract
The pattern of long-term GHRH administration capable of stimulating GH release without depleting pituitary GH content has been investigated using two experimental approaches. In experiment 1, recently weaned male lambs were treated for 3 weeks as follows: Group A) control; B) subcutaneous (sc) continuous infusion of GHRH (1200 mg/day) using a slow release pellet; C) the same as B plus 1 daily sc injection of long acting somatostatin (SS) (octreotide, 20 mg); D) 3 daily sc GHRH (250 mg) injections; E) 2 daily sc injections of GHRH (250 mg) and 2 of natural SS treated using sc osmotic minipumps (900 mg/day) alone or combined with a daily sc injection of octreotide (20 mg) for 4 weeks. Basal plasma GH levels were increased after chronic pulsatile GHRH treatment but not after any kind of continuous GHRH administration. This increment was maintained during the 3 weeks of experimentation and appeared accompanied by a pituitary GH content similar to controls. A marked GH response to the iv GHRH challenge was observed in controls and in lambs receiving both types of continuous sc GHRH infusions, whereas pulsatile sc GHRH-treated animals did not respond to the iv GHRH challenge in the first and second weeks of the study but did so in the third week of treatment. These data demonstrate that long-term pulsatile GHRH administration is capable of stimulating GH release in growing male lambs, without producing pituitary desensitization.
Resumen
Se estudia el efecto del patrón de administración a largo plazo de GHRH sobre la liberación de GH sin vaciar la hipófisis de esta hormona en corderos macho recién destetados. En el experimento 1 los animales se tratan durante 3 semanas como sigue: Grupo A) control; B) infusión continua subcutánea (sc) de GHRH (1200 μg/day) utilizando un pellet de liberación lenta; C) como el grupo B más 1 inyección sc diaria de somatostatina (Ss) de larga duración (octreotide, 20 μg); D) 3 inyecciones sc diarias de GHRH (250 μg); E) 2 inyecciones sc diarias de GHRH (250 μg) y 2 de SS natural (250 μg). En el experimento 2, los corderos se tratan de forma continua con GHRH usando minibombas osmóticas sc (900 μg/día) solas o combinadas con una inyección sc diaria de octreotide (20 μg) durante 4 semanas. Los niveles plasmáticos basales de GH aumentan después del tratamiento crónico con GHRH de forma pulsátil, pero no tras ninguna forma de administración continua de GHRH. Este aumento se mantiene durante las 3 semanas de experimentación y aparece acompañado de un contenido hipofisario de GH similar a los animales controles. Se observa una marcada respuesta de GH al bolo iv de GHRH en los corderos controles y los que recibieron los dos tipos de infusión contínua de GHRH, mientras que los animales tratados con GHRH sc de forma pulsátil, no responden a la inyeción iv de GHRH en la primera y segunda semanas de estudio, pero sí en la tercera semana de tratamiento. Estos datos demuestran que la administración a largo plazo de GHRH de forma pulsátil es capaz de estimular la liberación de GH en corderos macho en crecimiento, sin producir desensibilización hipofisaria.
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Pérez-Romero, A., De Lama, M.A.R., Granados, B. et al. Growth hormone response to long-term GH-RH administration in lambs. J. Physiol. Biochem. 56, 107–115 (2000). https://doi.org/10.1007/BF03179906
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DOI: https://doi.org/10.1007/BF03179906