Novel mechanisms of growth hormone regulation: growth hormone-releasing peptides and ghrelin

Growth hormone secretion is classically modulated by two hypothalamic hormones, growth hormone-releasing hormone and somatostatin. A third pathway was proposed in the last decade, which involves the growth hormone secretagogues. Ghrelin is a novel acylated peptide which is produced mainly by the stomach. It is also synthesized in the hypothalamus and is present in several other tissues. This endogenous growth hormone secretagogue was discovered by reverse pharmacology when a group of synthetic growth hormone-releasing compounds was initially produced, leading to the isolation of an orphan receptor and, finally, to its endogenous ligand. Ghrelin binds to an active receptor to increase growth hormone release and food intake. It is still not known how hypothalamic and circulating ghrelin is involved in the control of growth hormone release. Endogenous ghrelin might act to amplify the basic pattern of growth hormone secretion, optimizing somatotroph responsiveness to growth hormone-releasing hormone. It may activate multiple interdependent intracellular pathways at the somatotroph, involving protein kinase C, protein kinase A and extracellular calcium systems. However, since ghrelin has a greater ability to release growth hormone in vivo, its main site of action is the hypothalamus. In the current review we summarize the available data on the: a) discovery of this peptide, b) mechanisms of action of growth hormone secretagogues and ghrelin and possible physiological role on growth hormone modulation, and c) regulation of growth hormone release in man after intravenous administration of these peptides.

Síndrome de Turner: estado actual / Turner's syndrome: update

An up to date discusion concerning the Turner's syndrome is done in the present article

Growth acceleration in children with chronic renal failure treated with growth-hormone-releasing hormone (GHRH)

Growth retardation is a prominent clinical manifestation in children with chronic renal failure (CRF). Nine children with CRF (3 on conservative treatment; 3 on dialysis and 3 after renal transplantation) aged 1.6 to 14.0 (x+ SE: 8.1 + 1.4) years, were treated with twice daily subcutaneous injections of 26 + 2.4 mug/Kg/day growth-hormone-releasing-hormone [GHRH (1-29) NH2 Serono (Geref)] during 3 to 6 months. Mean serum urea and creatinine remained stable, although 2 patients on conservative treatment showed a moderate increase in serum creatinine. At the start of the study, heigth SDS was - 2.2 + 0.2 (x + SE), growth velocity was 4.5 + 1.0 cm/year (-2.3 + 0.6 DS for chronological age) and growth hormone (GH) response to acute GHRH test (1 mug/Kg IV) was 62 + 17.5 ng/ml. Five patients increased height velocity from 3.8 + 0.7 to 8.0 + 1.2 cm/year (paired t test, p < 0.05). The peak GH response to GHRH was significantly higher in the group of growth non-responders than in the responders (p<0.05). In conclusion, 5 out of 9 short children with CRF, 3 on conservative treatment, 1 on dialysis and 1 post renal transplantation, showed improved growth in response to GHRH therapy. No consistent effect on renal function was detected. GHRH may be an alternative therapy to increase grwth velocity in patients with CRF.

Consideraciones terapeúticas sobre la absorción de hormona de crecimiento humano / Therapeutic considerations on human growth hormone absorption

Se estudia la absorción de hormona de crecimiento humano (HGH) en 11 pacientes hipofisarios, con edades entre 10 y 18 años (XñDE 14,9 ñ2,6 años). A todos los pacientes se les administró a las 8 a.m. 4 unidades internacionales de HGH (crescormón) y se obtuvieron muestras de sangre para medir la hormona de crecimiento a los -30 y 0 minutos y a las 2,4,6,8,10,24 y 48 horas de administrado el medicamento. En esta prueba se evaluó inicialmente la vía intramuscular y un mes después la vía subcutánea. Al analizar los resultados no se encontraron diferencias significativas al comparar en cada momento del estudio los valores encontrados en las diferentes vías utilizadas ni al evaluar el incremento mayor alcanzado entre ambas vías. Además, se señala que ya a las 24 horas de administrada la HGH se encuentran valores plasmáticos similares a las cifras basales. Basados en nuestro resultados consideramos adecuado administrar la HGH diariamente, así como preferimos utilizar la vía intramuscular