Effects of Neonatal Administration of Octreotide, a Long-Lasting Somatostatin Analogue, on Growth Hormone Regulation in the Adult Rat

Abstract

The pulsatile pattern of GH secretion slowly develop in the postnatal period concomitantly with the dual network of GHRH and somatostatin (SRIH) hypothalamic neurons. We investigated whether an early postnatal treatment with a long acting SRIH analogue, octreotide, could affect maturation and subsequent operation of those networks in the adult rat. Octreotide administration (5 mu g/rat SC) every other day during the first 10 days of life resulted in growth retardation in the adult. In parallel, the amplitude of plasma GH secretory episodes in free moving unanesthetized animals was markedly reduced. The numbers of arcuate GHRH mRNA-containing and periventricular SRIH-mRNA containing neurons were not affected by the treatment. GHRH mRNA levels per neuron however was decreased by 30%, and median eminence GHRH stores by 50%. SRIH expression in the arcuate nucleus was also diminished, as was the number of 125I-SRIH labeled neurons in that nucleus. The effects of octreotide were compared to the hyposomatotropinemia induced by administration of monosodium glutamate (MSG), every other day during the first 10 days of life. Growth retardation and inhibition of GH secretory episodes in adult rats neonatally treated with MSG were slightly more pronounced than after octreotide. In contrast to octreotide, MSG induced a massive loss of GHRH neurons and a concomitant decrease in 125I-SRIH binding. Somatostatin did not protect GHRH neurons against the neurotoxic action of MSG since octreotide treatment did not further affect any of the parameters impaired by MSG. In conclusion, these experiments demonstrate that neonatally injected octreotide cannot counteract the toxic effect of MSG on arcuate neurons. However, a neonatal treatment with the SRIH agonist affects permanently growth rate and GH pulsatility. This effect is mediated in the hypothalamus by permanently impairing the neural networks that control GH secretion.