SummaryProlactin levels were measured in cord blood by radioimmunoassay in 57 premature infants between 26 and 36 weeks of gestation. The level of prolactin was in the range of 20 to 600 ng/ ml. Twenty-three of the infants subsequently developed respiratory distress syndrome (RDS). The mean cord prolactin in the infants with RDS was 140 + 30.7 ng/ml, whereas in the healthy infants it was 276.4 + 26.4 ng/ml. Cord prolactin levels less than 140 ng/ml were associated with a high incidence of RDS: of 25 infants with prolactin levels of less than 140 ng/ml, 19(76%) had RDS. Of the 34 healthy infants, 28(82%) had prolactin levels above 140 ng/ml. The highest levels (500 ng/ml) of prolactin in the group of infants with RDS were in two infants of diabetic mothers. The data suggest that prolactin might have a role in lung maturation in the human fetus. SpeculationProlactin is the latest hormone to be added to the list of hormones affecting lung maturation. Three groups have now reported a significant correlation between low cord prolactin levels and respiratory distress syndrome. The relative importance and mode of action of prolactin is unclear at present. Prolactin is present in very high concentration in amniotic fluid, and prolactin receptors are present in lung preparations. Prolactin might act as a direct trigger of lecithin synthesis or in a "chain reaction" along the hypothalamic-pituitary-adrenal axis. It could also be only an indicator of the degree of lung maturation. However, it is rapidly becoming clear that prolactin has a major role not only in lactation but also in fat metabolism, ion transport, and probably lung maturation.Survival of the newborn infant depends primarily on its ability to establish effective ventilation. This ventilation is directly related to the presence of pulmonary surfactant in sufficient quantity to ensure alveolar stability (2). The precise mechanism that regulates fetal lung maturation is not clear at Dresent. Acceleration of -~ ~ U surfactant synthesis by corticosteroids and thyroxine has been demonstrated both in ex~erimental animals (6. 17) and human subjects (5, 13). ow eve;, studies by ~e s h e r ' k t a i (14) suggest that cortisol is not a natural trigger of surfactant synthesis.We have shown that administration of prolactin to fetal rabbits in utero leads within two days to a 67% increase in lung lecithin content (1 I), and we have suggested, therefore, that prolactin may be a physiological trigger of surfactant synthesis and lung maturation. Ballard et al. (3) have been unable to repeat our findings in rabbit fetuses. However, first Hauth et al. (12) then we (15) and Gluckrnan et al. (9,10) have confirmed independently an association between incidence of respiratory distress syndrome (RDS) and low cord prolactin levels in premature infants. In this paper, we present our observations and compare the results with the other reports. MATERIALS AND METHODSThe subjects of this study were 57 premature infants admitted to the neonatal intensive care units of Georgetown Medical C...
Prolactin and thyroxine levels were measured by radioimmunoassay in cord blood of 61 premature infants of 26–36 weeks gestation. 30 of the infants subsequently developed respiratory distress syndrome (RDS). The infants who developed RDS had a mean cord prolactin level of 174.5 ± 24.5 ng/ml and a mean cord thyroxine level of 5.9 ± 0.4 μg/dl. In the 31 healthy infants, the mean cord prolactin and thyroxine levels were significantly higher (226.3 ± 25.8 ng/ml and 7.1 ± 0.4 μg/dl, respectively). The correlation coefficient between prolactin and thyroxine was r = 0.56 in infants with RDS (p < 0.0008). Both prolactin and thyroxine correlated with gestational age in the RDS group (r = 0.71 and 0.47, respectively). Discriminant analysis shows that the correlation between prolactin and thyroxine is independent of gestational age (r2 = 0.32, p < 0.05). There was no correlation between the levels of prolactin and thyroxine in infants without RDS. In the healthy group, the cord prolactin levels were significantly higher (p < 0.01) in female (335.8 ± 47.7 ng/ml) than in male infants (209 ± 17.2 ng/ml). Premature infants who develop RDS have significantly lower thyroxine and prolactin levels in cord blood than infants who remain healthy.
a n d P a u l Hamosh. (Spon. b y Gordon B . A v e r y ) Georgetown U n i v e r s i t y Medical C e n t e r , d e p t s . of P e d i a t r i c s a n d Physiology a n d B i o p h y s i c s . Washington DC .We h a v e r e c e n t l y s h o w n t h a t a d m i n i s t r a t i o n of p r o l a c t i n ( 1 m g p e r f e t u s ) to r a b b i t f e t u s e s l e a d s to a n i n c r e a s e in t h e concentration of l u n g dipalmitoyllecithin ( Hamosh, J . Clin. I n v e s t . 59: 1002,1977 In t h e p r e s e n t s t u d y w e h a v e t e s t e d t h e r e l a t i o n s h i p between s e r u m prolactin a n d c o r t i s o l l e v e l s a n d lung m a t u r i t y in p r e m a t u r e i n f a n t s .Prolactin a n d c o r t i s o l l e v e l s w e r e m e a s u r e d b y radioimmunoassay i n 40 p r e m a t u r e i n f a n t s b e t w e e n 26 a n d 37 w e e k s of gestation. Mixed c o r d blood w a s collected a t d e l i v e r y , c e n t r i f u g e d a n d t h e s e r a k e p t a t -20% u n t i l analysis. Prolactin l e v e l s r a n g e d from 20 to 600 n g / m l c o r t i s o l l e v e l s m e a s u r e d 25 to 350 n g / m l . C o r d p r o l a c t i n l e v e l s l e s s t h a n 140 n g l m l w e r e a s s o c i a t e d with a h i g h i n c i d e n c e of r e s p i r a t o r y d i s t r e s s s y n d r o m e (RDS); of 18 i n f a n t s with p r o l a c t i n l e v e l s less t h a n 140 n g l m l 16 (89%) h a d RDS. Only 27% of t h e i n f a n t s with RDS h a d p r o l a c t i n l e v e l s a b o v e 140 n g l m l . Two of t h e h i g h e s t l e v e l s i n t h i s g r o u p w e r e from infants with d i a b e t i c m o t h e r s . T h e r e w a s n o c o r r e l a t i o n b e t w e e n c o r d s e r u m p r o l a c t i n a n d c o r t i s o l l e v e l s or b e t w e e n c o r t i s o l l e v e l s a n d t h e i n c i d e n c e of RSD. T h e data s u g g e s t t h a t p r o l a c t i n might b e a t r i g g e r of l u n g maturation i n t h e h u m a n f e t u s . A t o t a l of 26 l i t t e r s were s t u d i e d . F e t u s e s from s a l i n e -i n j e c t e d c o n t r o l and d i a b e t i c l i t t e r s were examined a t 27.5 and 29.5 days g e s t a t i o n a l age. Pressure-volume c u r v e s were performed and s u rf a c t a n t from a l v e o l a r lavage f l u i d was q u a n t i f i e d on a s u r f a c e balance.Blood s u g a r s of d i a b e t i c does ranged from 175-400 mg/d throughout pregnancy a s compared w i t h 80-120 mg/dl i n t h e cont r o l s . :! P e d i a t r i c : and Medi--c i n e , C o l l . of Phys. and S u r g . , Columbia U n i v e r s i t y , New York. Fed. Proc. 36:630, 1977). To s t u d y t h e c e l l u l a r b a s i s of t h i s phenomenon, we h a r v e s t e d e n d o t h e l i a l c e l l s by p e r f u s i n g hu man umbilical c o r d s , r a b b i t and pig lungs and c a l f a o r t a s w i t h m i x t u r e of 0.1% c o l l a g e n a s e , 0.1% t r y p s i n and 1.0% chicken seru i n Hank's S o l u t i o n , and propagated t h e c e l l s i n medium 199. CE a c t i v i...
The uptake and metabolism of 3H-ρalmitate, 14C-choline, 14C-proline and 3H-glucosamine were studied in lung slices prepared from rats aged 2–12 days. Palmitate incorporation increased from 18.2 ± 2.8 nmol/mg protein/h 2 days before birth to 40.0 ± 4.0 nmol/mg protein/h 3 days after birth, and decreased to 24.0 ± 2.3 nmol/mg protein/h at 12 days of age, it remained at the same level in the adult lung. At all ages tested, more than 75% of the palmitic acid taken up by the lung was in esterified form. Incorporation of palmitic acid into lecithin was highest 1 day after birth. Choline incorporation into lecithin increased eightfold between 2 days before and 1 day after birth (from 0.45 ± 0.12 to 3.75 ± 0.25 nmol/mg protein/h, respectively) and decreased 60% by 12 days of age. There was no difference between the incorporation rate at 12 days and that in the adult lung (1.52 ± 0.15 nmol/mg protein/h). Total lung phospholipid increased 220% between 2 days before birth and the day of birth, and changed little thereafter. Phosphatidyl choline made up 50–60% of lung phospholipids at all ages. Proline incorporation into lung protein was highest in the perinatal period (0.57–0.58 nmol/mg protein/h 2 days before and 1 day after birth) and decreased rapidly thereafter. Glucosamine incorporation was highest in the fetal lung (0.84 ± 0.05 nmol/mg protein/h) and decreased 67% 1 day after birth, the incorporation remained between 0.1 and 0.2 nmol/mg protein/h thereafter (from 3 days to adult age). The data presented show that in the rat lung the biosynthesis of structural components and of surfactant is highest during the immediate perinatal period.
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