SummaryThe possibility that caffeine, a central nervous system stimulant used in neonatal apnea, may produce acute or chronic changes in growth hormone (GH), thyroxine (T4) and thyrotropin (TSH) was studied in the newborn rat. Five-day-old rats were separated into three groups: control (0) group receiving saline, Group I (low dose caffeine) receiving 5 mg/kg and Group I1 (high dose caffeine) receiving 50 mg/kg. Acute effects were studied at 2, 4, and 24 h after injection. Chronic effects were studied 24 h after the last of 10 daily injections. GH, T4, and TSH were measured by radioimmunoassay and caffeine by high pressure liquid chromatograph. GH was increased at all times and all doses after a single injection of caffeine. After chronic therapy, the increase in GH was small, suggesting depletion of pituitary reserve. A high dose of caffeine had a biphasic effect on T4 with an increase at 4 h and a decrease at 24 h. Thyrotropin-releasing hormone (TRH)-induced TSH release at 24 h was not influenced by caffeine administration. Chronic caffeine therapy stimulated both T4 and TSH; however, TRH-stimulated TSH release was decreased, suggesting that chronic therapy may blunt pituitary TSH response. AbbreviationsGH, growth hormone PDE, phosphodiesterase T3, triiodothyronine T4, thyroxine TRH, thyrotropin releasing hormone TSH, thyrotropinBesides the stimulant effect of the methylxanthines on the central nervous system and on cardiac inotropy and chronotropy, these compounds exert a variety of hormonal and metabolic effects. The administration of two methylxanthines, caffeine and theophylline, to adult rats results in decreased GH, TSH, TQ and thyroxine T4 serum levels (29). But in in vitro isolated organ preparations, caffeine increases T4 (3) and TSH (28) ) did not find any modification in basal GH after aminophylline, whereas, Ensinck et al. (17) described a decrease in GH serum level. After a low dose of oral caffeine given to adult healthy men, neither GH, TSH nor Tg were modified (30). Because caffeine is currently used in the premature neonate for the treatment of apnea, we evaluated the changes in GH, T4, and TSH after caffeine in the newborn rat. MATERIALS AND METHODSFive-day-old male Sprague-Dawley rats were obtained from the Canadian Breeding Farm, St. Constant, Quebec. Two sets of experiments were respectively designed to evaluate the acute and the chronic effects of caffeine. Each set used three groups: a control group, which received saline; a low dose caffeine group, which received 5 mg/kg of caffeine dissolved in saline; and a high dose caffeine group, which received 50 mg/kg. Caffeine (37) or saline was injected intraperitoneally in a volume of 0.05 ml/rat. Each group consisted of 30-35 rats. In the acute experiment, the animals were sacrificed at various time intervals after a single injection of saline or caffeine: 2, 4, and 24 h. In the chronic experiment, animals were injected daily for a 10 day period. They were sacrificed 24 h after the last injection. The rat pups were kept with their suckling mot...

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The effect of dehydroepiandrosterone (DHA) and LRH on estrogen and progesterone production by cultured placental cells has been investigated. Placental monolayer cultures were established by trypsin dispersion of term placental villi and were maintained for 5 days in culture medium containing either no steroid or 10(-7) - 10(-5)M DHA, DHA sulfate (DHAS), or 16 alpha-hydroxy-DHA (16 alpha-OH DHA), in all cases with and without the addition of 2 X 10(-7) or 2 X 10(-6)M LRH. The cultures were changed every 24 h, and the media collected were analyzed for estrogen and progesterone by RIA. 17 beta-Estradiol production was dependent on the presence of DHA or DHAS in the medium and increased in proportion to the concentration of precursor added. Similarly, estriol was produced in proportion to the amount of 16 alpha-OH DHA added to the medium. At the same time, high concentrations (10(-5) M) of DHA and DHAS, but not 16 alpha-OH DHA, markedly suppressed progesterone production. LRH had an inhibitory effect on both progesterone and estrogen output by the cultures. These studies suggest that not only the fetus, through its increasing adrenal production of DHA and DHAS toward term, but the placenta itself, through its production of LRH, could modulate placental steroid synthesis.