The present study was undertaken to establish the developmental pattern of urinary endothelin-1 (ET-1) excretion and to define its possible role in mediating pathophysiological changes related to perinatal asphyxia/infection and dopamine treatment. Urinary ET-1 levels were measured by radioimmunoassay in 7 full-term neonates (mean gestational age 39.3 weeks) on days 1, 3 and 5, and in 9 pre-term neonates (mean gestational age 30.8 weeks) on days 1, 3, 5, 7 and weekly thereafter for 5 consecutive weeks. The results were compared with those of three age-groups of 30 normal children (4-8 years, 9-12 years and 13-18 years); each group consisted of 10 children. The influence of severe cardiopulmonary distress (n = 16, mean gestational age 33.9 weeks, post-natal age 3.3 days) and dopamine administration in a dose of 2 micrograms/min per kg (n = 10, mean gestational and post-natal ages 32.1 weeks and 5.6 days, respectively) were also studied. In full-term infants, ET-1 concentration fell from 34.3 +/- 1.8 pmol/l on day 1 to 21.5 +/- 1.5 pmol/l on day 5 (P < 0.01). In premature infants its absolute value and its post-natal fall were similar in the 1st week and no further change occurred in weeks 2-5; it stabilized at levels between 17.1 +/- 2.2 and 16.7 +/- 1.7 pmol/l. These concentrations tended to be lower than those of 25.5 +/- 1.3, 23.0 +/- 1.0 and 26.2 +/- 0.7 pmol/l measured in three groups of older children.(ABSTRACT TRUNCATED AT 250 WORDS)
The secretion and release of prolactin from the anterior pituitary is under the tonic inhibitory control of endogenous dopamine produced in the central nervous system. Exogenous dopamine inhibits prolactin secretion by reaching the pituitary via the portal circulation, and the hypolactotropic effect of dopamine infusion has been documented in all age groups in humans. However, the maturation of lactotroph sensitivity to dopaminergic inhibition has not been studied. Therefore, we followed the changes in serum prolactin concentrations before, during, and after dopamine infusion in 19 sick preterm infants with a mean gestational age of 30.6 ± 0.6 weeks during the first 3 days of life, and examined the relationship of the hypolactotropic effect of dopamine to gestational age and birth weight in this patient population. As expected, dopamine therapy resulted in a decrease in mean serum prolactin from 89.4 ± 9.5 to 58.6 ± 9.1 µg/l (p < 0.05) with a return of the serum prolactin concentration to the pretreatment level 2–6 h after discontinuation of drug administration (98.3 ± 11.7 µg/l, p < 0.05). However, simple regression analysis of the individual data revealed that the magnitude of the dopamine-induced decrease in serum prolactin was significantly influenced by gestational age (p = 0.006) and birthweight (p = 0.037). Thus, our findings provide evidence for the maturation of pituitary lactotroph sensitivity to dopaminergic inhibition in the preterm human neonate.
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