Pediatr. Res. 15: 850-852 (1981) bromoergocriptine lecithin fetus lung Effects of Bromocriptine Administration to Pregnant Rabbits upon Fetal Lung Maturation GUSTAVO A. GIUSSI,'2" GUSTAVO BALLEJO, RAUL BUSTOS, AND ROBERTO CALDEYRO-BARCIA Latin American Center of Perinatology and Human Development, Pan American Health Organization/ World Health Organization. Montevideo, Uruguay Summary If endogenous prolactin secretion is important in normal devel- opment of fetal lung surfactant, the inhibition of its secretion should be associatedwith delayed maturation of fetal lung. We therefore studied the effect of bromoergocriptine adminis- tration to pregnant rabbits upon lecithin content of fetal lung washes. The does were treated since the 27th day of gestation with either Mesilate of 2-Bromo-a-ergocriptine (C32H.,0BrN~05. CH3S03H) (Bromocriptine) (Parlodel, Sandoz) (1 mg/kg/day) or solvent twice daily until delivery. The newborns were killed immediately by intraperitoneal ad- ministration of sodium penthobarbital and tracheostomized; then lung washes were performed. The extracted lipids were plated and run on heat-activated thin layers of silica gel H. Lecithin was eluted, and phosphorus deter- mination was performed. The level of lecithin phosphorus in the lung washes of the fetuses whose mothers received Bromocriptine was x = 2.24 + 0.39 pg/g dry lung weight, whereas that of fetuses of control does was x = 6.93 + 2.64 pg/g dry lung weight ( P < 0.001). The mean body weight of the fetuses from treated mothers was 38.22 + 6.39 g whereas that of fetuses from control rabbits was 47.63 + 6.94 g ( P < 0.001). The mother's body weight gain from days 26 to 30 in Bromo- criptine-treated rabbits was 156.11 + 99.4 g, whereas that of controls was 374.38 f 166.21 g (P < 0.01). Speculation Prolactin could be involved in the normal biochemical develop ment of the lung and also be necessary for a normal weight gain of mother and fetuses during the last stage of gestation. Biochemical maturation of the fetal lung as revealed by an increase in lecithin production occurs towards the end of gestation. This process is influenced by the administration of hormones such as glucocorticoids (7, 8), thyroxine (24), estrogens (16), and prolactin (14). Also, it has been shown that insulin (19), epidermal growth factor (4). /3-adrenergic agents (25), and cholinergic drugs (5) could affect lung maturation. Recently, it has been shown that there is a relationship between cord prolactin levels and respiratory distress syndrome incidence (e.g., low cord prolactin is associated with high incidence of this syndrome) (1 1, 12, 15,21,22). This observation would suggest that endogenous prolactin could be involved in the process of lung maturation. In this study, we postulated that if endogenous prolactin secre- tion is important in normal development of fetal lung surfactant, the inhibition of its secretion should be associated with delayed maturation of fetal lung. We therefore studied the effect of bromoergocriptine adminis- tration to pregnant rabbits upon lecithin content of fetal lung washes. MATERIALS AND METHODS Time dated pregnant Californian rabbits (eight controls and nine bromocriptine treated) were used in this study. They were mated between 10 AM and 2 PM, and this day was taken as day 0 of gestation. The rabbits were fed ad libitum with water and rabbit food. The does were treated since the 27th day of gestation with either Bromocriptine (Parlodel, Sandoz) (I mg/kg/day) or solvent twice daily until delivery. Delivery was performed by hysterotomy on day 30 of gestation. The newborns were killed immediately by intraperitoneal ad- ministration of sodium penthobarbital before amniotic sac rupture and weighed. They were exsanguinated by cutting the abdominal aorta, and tracheotomy was performed in five of them. Once tracheostomized, lung washes were performed as previously de- scribed (3). Briefly, each pair of lungs was gently lavaged with 2 ml of 0.9% saline solution (20°C) five times. The washings were pooled by litter groups. After the lavages, the lungs were dried in a desiccator at 100°C until their weight was constant. The alveolar washes were stirred with an equal volume of methanol and lipids extracted with two volumes of chloroform (10). The extracted lipids were plated and run on heat-activated thin layers of silica gel H containing 5% ammonium sulphate. The plates were developed using chloroform-methanol-acetic acid- Hz0 (390- 150-48-24 p/p). After development of the chromatograms, the plates were charred at 280°C for 10 min to visualize compounds. Lecithin was eluted, and phosphorus determination was performed by the method of Bartlett (2). The statistical analysis was done by the t test. RESULTS The lecithin phosphorus concentrations in lung washes of both groups are shown in Figure 1. The level of lecithin phosphorus in the lung washes of the fetuses whose mothers received Bromocrip- tine was R = 2.24 -+ 0.39 pg/g dry lung weight, whereas that of fetuses of control does was X = 6.93 -t 2.64 pg/g dry lung weight. The difference was statistically significant (P < 0.001). It was also observed that Bromocriptine administration caused a reduction in body weight of the fetuses and in the weight gain of the does (Table 1). The mean body weight of the fetuses from treated mothers was 38.22 -t 6.39 g whereas that of fetuses from control rabbits was 47.63 + 6.94 g. The t test showed that the difference was statistically significant (P < 0.001). The mother body weight gain from days 26 to 30 was signifi- cantly lower in the treated animals. The mean body weight gain