Delbert A. Fisher

Acute release of thyrotropin in the newborn

Measurements of serum thyrotropin (TSH) concentrations were conducted in maternal and fetal blood during labor and delivery and the early postnatal and neonatal periods. Mean TSH concentration was significantly higher in cord blood (9.5 muU/ml) than maternal blood (3.9 muU/ml), a finding suggesting a fetal-maternal TSH gradient at term. Serum TSH concentration in the newborn increased rapidly to mean levels of 60 muU/ml at 10 min and 86 muU/ml at 30 min of age. Between 30 min and 3-4 hr serum levels decreased rapidly, then fell more gradually to a mean concentration of 13 muU/ml at 48 hr. The half-time of the decrease in serum TSH concentration between 30 and 90 min was 77 min, a value slightly greater than the half-time of disappearance of radioiodinated TSH measured in adults. This indicates that the early high rate of TSH secretion in the newborn ceases by 30 min, and that the rapid rise and fall in serum TSH concentrations may represent release of stored pituitary TSH. A more chronic TSH hypersecretion persisted throughout the first 24-48 hr of extrauterine life. Measurements of serum PBI concentrations were conducted in a separate group of maternal and cord blood samples and in the newborn infants during the first 48 hr of extrauterine life to relate the TSH and serum hormonal iodine concentration changes. Serum protein-bound iodine (PBI) concentrations were similar in maternal and cord blood, increased significantly by 4 hr of age in the newborn, and peaked at about 24 hr, presumably in response to the TSH hypersecretion. The pattern of TSH hypersecretion was similar in infants delivered vaginally and by caesarean section. Maternal serum TSH concentrations were stable throughout the perinatal period. Warming the infants at 99-103 degrees F during the first 3 hr of life did not prevent the early, acute release of thyrotropin. Cooling of warm infants at room temperature (72-78 degrees F) between 3 and 4 hr resulted in a decrease in mean rectal temperature of 3.3 degrees F and produced a significant increment in serum TSH concentration. These data suggest that the mechanism of the early, acute release of thyrotropin in the newborn may involve a potent stimulus other than cooling. However, the increase in serum TSH stimulated by delayed (3-4 hr) cooling indicates that neonatal hyperthyroxinemia is, at least, augmented by extrauterine cooling. Thus, cold exposure is capable of increasing TSH secretion in humans.

Plasma catecholamine concentrations in infants at birth and during the first 48 hours of life

A radioenzymatic assay was used to measure plasma concentrations of the catecholamines, norepinephrine, and epinephrine in the perinatal period. Samples were obtained at birth from the umbilical artery and vein of infants born by vaginal and by cesarean section delivery; from peripheral venous samples of normal infants during the first 48 hours of life; and from peripheral venous samples of mothers prior to delivery. Concentrations of NE and E were elevated in umbilical samples, with umbilical artery levels exceeding umbilical venous concentrations. Umbilical plasma CAT concentrations were similar in vaginal and cesarean section delivered infants. Plasma concentrations of NE consistently predominated over E in all samples from neonates. Plasma CAT concentrations rapidly fell from cord levels within 15 minutes of delivery and remained at a lower plateau during the first three hours of life. By 12 hours of age plasma CAT concentrations fell to the levels of supine adult resting concentrations. Maternal plasma CAT concentration prior to delivery demonstrated a predominance of E over NE. These elevations of plasma CAT in the early neonatal period may play a rola in nonshivering heat production as well as in cardiovascular alterations associated with birth.

Comparison between epidermal growth factor, transforming growth factor-α and EGF receptor levels in regions of adult rat brain

Examination of adult rat brain regions by specific radioimmunoassays revealed a widespread distribution of transforming growth factor-alpha (TGF-alpha), but not epidermal growth factor (EGF), the peptide that had previously been reported to be present in rodent brain. Polyadenylated RNA samples from the different regions of rat brain were analyzed by Northern blot to identify mRNA species encoding precursor proteins for EGF (preproEGF), TGF-alpha (preproTGF-alpha), and the EGF/TGF-alpha receptor. The results indicate that TGF-alpha is the most abundant ligand for the EGF/TGF-alpha receptor in most parts of the brain analyzed. Message for preproEGF was only detectable after prolonged autoradiographic exposure; levels of preproEGF mRNA were between two and three orders of magnitude lower in brain than those expressed in control tissue (kidney), and one to two orders of magnitude lower than preproTGF-alpha mRNA levels in all brain regions. These results were confirmed by analysis of mRNA by RT/PCR, and support the hypothesis that expression of preproEGF mRNA in the brain is limited to smaller discrete areas, whereas preproTGF-alpha gene expression is almost ubiquitous.

Possible mechanisms of high blood levels of vasopressinduring the neonatal period

who was old enough to be given the Bender-Gestalt test showed highly significant errors suggestive of perceptuomotor difficulties. No association could be found between IQ scores, respiratory distress syndrome, or hyperbilirubinemia. No inordinate delay in the placement of the venous catheter was observed in those with IQ < 90, nor was there any difference in the mean caloric intake of children with IQ < 90 when compared to the caloric intake of Group A as a whole. In Group B, the mean IQ of patients was 99.3, with their control children having a mean IQ of 99.1.

Oxytocin Concentrations during the Neonatal Period

Plasma oxytocin levels in the umbilical artery (UA) exceeded umbilical venous levels in newborn infants delivered by cesarean section (without maternal labor) (p less than 0.05) and following labor (NS). There was an initial rapid decrease in oxytocin concentration from UA levels to those in peripheral venous blood by 30 min of page. Plasma oxytocin levels for breast-fed and formula-fed infants remained elevated over adult basal levels (1.7 +/- 0.3 mu U/ml) throughout the 4-day study period. Mean oxytocin concentration measured in breast milk from 10 mothers 2-4 days following vaginal delivery was 10.0 +/- mu U/ml. The stimulus for fetal and neonatal oxytocin secretion remains obscure, but continues beyond the period of birth.

Epidermal Growth Factor in Synaptosomal Fractions of Mouse Cerebral Cortex

Abstract: Using a specific and sensitive epidermal growth factor radioimmunoassay (EGF‐RIA) we measured EGF concentrations in whole brain, cerebral cortex, and cerebral cortical synaptosomal (pinched‐off presynaptic nerve terminals) fractions of 26‐day‐old mouse brain. The relative EGF concentration in synaptosomal fractions was significantly greater than the growth factor concentrations in whole brain or cerebral cortex. Intracerebral injection, in an amount of EGF, several‐fold greater than whole brain EGF content, did not appreciably increase synaptosomal EGF concentration, suggesting that no artifact was involved. The high synaptosomal EGF content suggests a neurotransmitter or a neuromodulator role for EGF in the CNS.

Immunoelectron microscopy of epidermal growth factor in mouse kidney

We recently have reported the immunolocalization of epidermal growth factor (EGF) in mouse kidney by light microscopy. In the present study, we have investigated the ultrastructural localization of EGF by the preembedding immunoperoxidase method for electron microscopy. EGF immunoreactivity was present on the apical plasma membrane of the cells of the thick ascending limb of Henle and the distal convoluted tubule. The macula densa, by contrast, lacked immunoreactivity. Based on functional evidence, a possible regulatory role for EGF in the membrane transport in the distal nephron has been suggested.

Sex differences in lung and adrenal neurosympathetic development in rabbits.

To assess the possible mechanism for the increased incidence and severity of the respiratory distress syndrome (RDS) in male versus female infants, we studied neurosympathetic development in the lung and adrenal glands in male and female fetal and newborn rabbits. Tissue levels of catecholamines, norepinephrine (NE), epinephrine (E), and dopamine (DA) were measured using a sensitive radioenzymatic assay. Beta adrenergic receptor development in the lung was studied using the tritiated radioligand dihydroalprenolol. Neurosympathetic innervation of the lung was assessed by measuring tissue NE levels, which increased gradually from 27-day fetuses to 8-day-old newborns. Sex differences were not significant. Lung beta-receptor number was significantly elevated in females as compared with males at each gestational age and throughout the neonatal period (p less than 0.005). Adrenal gland content of E, NE, and DA increased exponentially with advancing developmental age (each p less than 0.005). Adrenal E was significantly (p less than 0.01 elevated in female as compared with male fetuses, as was the proportion of E. Adrenal NE and DA were similar in male and female fetuses. Sex differences were not significant in the newborn animals. The significant relative delay in adrenal medullary and lung beta-receptor matration may relate to the male susceptibility to neonatal morbidity and neonatal RDS.

Human nerve growth factor: Lack of immunocrossreactivity with mouse nerve growth factor

Abstract Human β-nerve growth factor (hNGF) was purified from term human placenta. The biological potency of hNGF in the chick dorsal root ganglion assay did not differ significantly from that of mouse NGF (mNGF). Molecular weight determinations of mNGF and hMGF were also similar. No immunological crossreactivity was noted between hNGF, at a concentration of 100 μg/ml, and mNGF in a radioimmunoassay for mNGF using 6 different antisera to mNGF. hNGF shares several properties with mNGF but is immunological distinct. The results of studies in man using antisera to mNGF should be interpreted with caution.

Differential hormonal response of epidermal growth factor concentration in the developing mouse: Synergism of triiodothyronine and dexamethasone in epidermal maturation

The hormonal regulation of epidermal growth factor concentration in neonatal mouse skin and submandibular gland is examined by radioimmunoassay. The results show triiodothyronine but not dexamethasone effects an unequivocal elevation in skin EGF content. In contrast, the neonatal submandibular gland is hormonally unresponsive during this period. Combined therapy with T3 and dexamethasone produces precocious incisor eruption compared to the effect of either hormone alone. The mechanism of this synergistic acceleration of an EGF-related developmental event is unknown.