EFFECTS OF NEONATAL ADMINISTRATION OF OCTREOTIDE, A LONG-LASTING SOMATOSTATIN ANALOG, ON GROWTH-HORMONE REGULATION IN THE ADULT-RAT

The pulsatile pattern of GH secretion slowly develop in the postnatal period concomitantly with the dual network of GHRH and somatostatin (S RIH) hypothalamic neurons. We investigated whether an early postnatal treatment with a long acting SRIH analogue, octreotide, could affect m aturation 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 G HRH mRNA-containing and periventricular SRIH-mRNA containing neurons w ere not affected by the treatment. GHRH mRNA levels per neuron however was decreased by 30%, and median eminence GHRH stores by 50%. SRIH ex pression in the arcuate nucleus was also diminished, as was the number of I-125-SRIH labeled neurons in that nucleus. The effects of octreot ide were compared to the hyposomatotropinemia induced by administratio n of monosodium glutamate (MSG), every other day during the first 10 d ays of life. Growth retardation and inhibition of GH secretory episode s in adult rats neonatally treated with MSG were slightly more pronoun ced than after octreotide. In contrast to octreotide, MSG induced a ma ssive loss of GHRH neurons and a concomitant decrease in I-125-SRIH bi nding. Somatostatin did not protect GHRH neurons against the neurotoxi c action of MSG since octreotide treatment did not further affect any of the parameters impaired by MSG. In conclusion, these experiments de monstrate that neonatally injected octreotide cannot counteract the to xic effect of MSG on arcuate neurons. However, a neonatal treatment wi th 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.