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Biomedical subjects

M G Ervin

Publications and source records attributed to M G Ervin.

At least 73 records · Page 4Linked to original sources

Ovine fetal lung fluid response to atrial natriuretic factor.

The fetal lung is an important site of fluid production and is postulated to serve a regulatory role in fetal fluid balance. To assess the role of atrial natriuretic factor on fetal lung liquid production, we studied the effect of intravenous atrial natriuretic factor infusion on tracheal fluid production in fetal sheep with chronic vascular and tracheal catheters. Ovine fetuses (mean gestation = 130 days +/- 1 day) received successive 40-minute intravenous infusions of increasing doses of synthetic fragment 1-28 atrial natriuretic factor (5, 25, and 100 ng/min.kg-1). In response to the 25 ng/min.kg-1 infusion, fetal tracheal fluid production decreased from 1.2 +/- 0.3 ml/10 min to 0.6 +/- 0.2 ml/10 min (p less than 0.05), and remained suppressed during the 100 ng/min.kg-1 infusion (0.5 +/- 0.2 ml/10 min). There was a significant inverse correlation between tracheal fluid production and fetal plasma atrial natriuretic factor levels (r = -0.61, p less than 0.001). Basal tracheal fluid sodium and potassium concentrations (147 +/- 1 mEq/L and 5 +/- 1 mEq/L) and osmolality (291 +/- 3 mOsm) did not change during the atrial natriuretic factor infusion periods. The observation that atrial natriuretic factor acts to decrease fetal lung fluid production suggests that atrial natriuretic factor may be important in the fetal adaptive response to extrauterine life.

Animals↗

Stimuli for fetal swallowing: systemic factors.

Although the fetal gastrointestinal tract is believed to be a major site of amniotic fluid absorption, there is little information with regard to the acute regulation of fetal swallowing. A model for the study of ovine fetal swallowing was developed to incorporate electromyograms, an esophageal flow probe, and a computer data acquisition and analysis program. The fetal swallowing responses to two primary thirst stimuli, plasma hyperosmolality and angiotensin II, were studied. On alternate days, chronically prepared fetal lambs (131 +/- 2 days) received an intravenous infusion of angiotensin II (100 ng/kg per minute) or bolus injections (3 ml) of 0.15 and 3.97 mol/L saline solution. In response to the angiotensin II infusion, fetal systolic (49.3 to 64.7 mm Hg; p less than 0.05) and diastolic (31.1 to 40.5 mm Hg; p less than 0.05) blood pressures significantly increased. However, fetal swallowing did not change from basal rates of 0.85 swallows per minute and a net esophageal flow of 0.98 ml/min. In response to the injection of 3.97 mol/L saline solution, fetal plasma osmolality increased (292 to 306 mOsm; p less than 0.05) and subsequently decreased to 300 mOsm at 15 minutes after the injection. Within 1 minute after injection of the hypertonic saline solution, fetal swallowing activity (6.0 swallows per minute; p less than 0.05) and net esophageal flow (2.4 ml/min; p less than 0.05) significantly increased. Swallowing returned to basal values within 5 minutes after the injection. The data indicate that ovine fetal responses to osmolar thirst challenges are intact at 130 days' gestation. Fetal swallowing and thus amniotic fluid volume may be affected by fetal responses to in utero stimuli.

Angiotensin II↗

Developmental changes in adrenergic regulation of fetal arginine vasopressin secretion.

Fetal adaptation to the extrauterine environment is associated with profound alterations in pulmonary, renal, and cardiovascular functions. Coincident with these changes are a variety of endocrine responses including concomitant increases in plasma catecholamine and arginine vasopressin (AVP) levels. In view of the demonstrated interaction between the sympathoadrenal system and the neurohypophysis in adult mammals, we questioned whether increases in plasma catecholamine levels in the fetus affect fetal plasma AVP levels and whether catecholamine-AVP interactions change developmentally. Chronically catheterized fetal lambs at either 131 +/- 1 (preterm) or 142 +/- 1 days (term) received graded infusions of either epinephrine (E) or norepinephrine (NE) at rates of 0.04, 0.2, 0.75, 1.5, and 3.0 micrograms.min-1.kg-1 during successive 40-min infusion periods. Plasma AVP concentrations in term animals significantly increased (1.4 +/- 0.1 to 5.1 +/- 1.6 pg AVP/ml) in response to E infusion of 0.75 microgram.min-1.kg-1 or greater. The log-linear dose response curves for each animal were used to determine the minimum plasma E concentration required to stimulate AVP secretion or "threshold." The mean plasma E threshold for AVP secretion was significantly lower in term animals (1.4 +/- 0.4 ng/ml) than in preterm animals (6.6 +/- 0.9 ng/ml). Plasma E levels were positively correlated with plasma AVP levels (r = 0.90) above the threshold value in both groups. Changes in plasma AVP levels were observed in preterm or term animals in response to NE only at the highest infusion rate studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Vasopressin levels and pediatric head trauma.

The syndrome of inappropriate secretion of antidiuretic hormone is associated with head trauma; however, there are no reports concerning vasopressin levels in pediatric patients with head trauma. Urine vasopressin in eight children (mean +/- SEM, age 7.5 +/- 1.6 years, range 1 to 15 years) was measured by radioimmunoassay during their hospitalization for head trauma. Urine vasopressin values for ten healthy children (mean age 5.4 +/- 1.3 years) and for eight children hospitalized for systemic antibiotic treatment of infections (age 5.9 +/- 1.8 years) also were obtained. Urine vasopressin, urine and serum sodium concentration and osmolality, urea nitrogen, creatinine, and fluid intake were measured within 24 hours of admission and daily for the following two days. For the first three days following head trauma, mean urine vasopressin levels in pediatric patients with head trauma were increased (P less than .05) compared with those of healthy children. Despite fluid restriction to 85% of maintenance level, 25% of patients with head trauma exhibited the clinical syndrome of inappropriate secretion of antidiuretic hormone (hyponatremia, increased urinary sodium, diminished serum osmolality, and urine osmolality greater than serum osmolality). Urine osmolality greater than 800 mosm/kg was associated with markedly increased urine vasopressin levels (200 to 1,650 pg/mL); children with this finding may be at particular risk for the syndrome of inappropriate secretion of anti-diuretic hormone without restrictive water intake.

Adolescent↗

Ovine fetal lung fluid response to intravenous saline solution infusion: fetal atrial natriuretic factor effect.

The fetal lung, a significant source of in utero fluid production, has been postulated to serve a regulatory role in maintenance of fetal body fluid homeostasis. Whereas the fetus responds to intravascular saline solution infusions with increased urine output, the fetal lung fluid response to this stimulus is unclear. Tracheal fluid output was measured in four chronically catheterized ovine fetuses (mean gestation, 129 +/- 1 days) subjected to successive 40-minute intravenous 0.9% saline solution infusions at rates of 0.5 and 1 ml/min/per kilogram of body weight. Tracheal fluid output decreased significantly (1.7 +/- 0.1 to 1.1 +/- 0.1 ml/10 min, p less than 0.01) during the infusion and returned to basal levels during the recovery period. Lung fluid osmolality and electrolyte concentration did not change. Fetal plasma atrial natriuretic factor increased significantly in response to the saline solution infusion (364 +/- 90 to 790 +/- 286 pg/ml, p less than 0.05) and returned to basal levels during the recovery period. There was a significant inverse correlation between plasma atrial natriuretic factor levels and tracheal fluid output. These results suggest that increased fetal plasma atrial natriuretic factor decreases lung fluid production. Lung fluid does not appear to compensate for fetal body water excess. Rather, lung fluid production appears to promote intrauterine pulmonary growth and to facilitate the transition to the extrauterine environment.

Animals↗

Fetal plasma and renal responses to ruminal fluid.

Amniotic fluid homeostasis is dependent on a balance of fetal fluid production and absorption. The fetal gastrointestinal tract is believed to resorb 500 to 1000 ml of amniotic fluid per day during 7 to 10 bouts of swallowing activity. However, the impact of ruminal fluid on fetal plasma composition and fluid homeostasis is largely unknown. Seven ovine fetuses (120 +/- 1 day) received intraruminal infusions of 0.9% or 3% saline solution on alternate days. In response to successive 40-minute intraruminal infusions of 0.9% saline solution (0.5 and 1.0 ml/kg/min), there was no change from basal levels of fetal plasma osmolality (295.7 +/- 2.9 mosm), plasma arginine vasopressin (1.45 +/- 0.29 pg/ml), urine osmolality (150 +/- 8 mosm), or urine volume (0.49 +/- 0.10 ml/min). In response to the 3% saline solution infusion, significant increases were noted in fetal plasma osmolality (295.4 +/- 3.1 to 302.6 +/- 2.6 mosm), plasma arginine vasopressin (1.77 +/- 0.31 to 4.84 +/- 0.79 pg/ml), and urine osmolality (157 +/- 13 to 342 +/- 25 mosm), whereas fetal urine volume significantly decreased (0.35 +/- 0.05 to 0.15 +/- 0.06 ml/min). These results indicate that hypertonic, but not isotonic, saline solution infusion into the fetal gastrointestinal tract may affect fetal plasma composition and urine production. Under conditions of significant plasma to luminal osmotic gradients, fetal gastrointestinal water and electrolyte transfer may be more rapid than can be compensated by either fetal renal function or placental equilibration.

Animals↗

Maternal dehydration-rehydration: fetal plasma and urinary responses.

Pregnant women may be exposed to exercise, thermal, or gastrointestinal (hyperemesis) water loss, all of which commonly induce a greater than 10 mosmol increase in plasma osmolality. Although fetal osmolality is dependent on maternal osmolality, the impact of maternal dehydration and subsequent maternal rehydration on the fetus has not been explored. Five pregnant ewes with singleton fetuses (136 +/- 1 day) were water deprived for 36 h resulting in a significant increase in plasma osmolality (298 +/- 3.4 to 313 +/- 5.0 mosmol). In response to maternal dehydration, fetal plasma osmolality (297.0 +/- 4.1 to 309.3 +/- 4.1 mosmol), arginine vasopressin (AVP) levels (1.5 +/- 0.2 to 7.9 +/- 1.0 pg/ml), hematocrit (35.1 to 38.6%), and urine osmolality (161.3 +/- 10.7 to 348.9 +/- 21.9 mosmol) significantly increased. Subsequently, ewes were rehydrated over 4 h with intravenously infused 0.45% saline (20 ml.kg-1.h-1). In response to maternal rehydration, maternal and fetal plasma osmolality decreased to basal values (298.9 +/- 3.2 and 300.1 +/- 3.8 mosmol, respectively) and fetal glomerular filtration rate (1.72 +/- 0.30 to 3.08 +/- 0.66 ml/min) and urine volume significantly increased (0.33 +/- 0.02 to 0.71 +/- 0.13 ml/min). However, fetal hematocrit (37.4%), plasma AVP (3.1 +/- 0.9 pg/ml), and urine osmolality (255.4 +/- 28.8 mosmol) did not return to basal levels during the observation period. These results demonstrate fetal hyperosmolality, blood volume contraction, AVP secretion, and altered urine production in response to maternal dehydration. Despite maternal rehydration and normalization of maternal and fetal plasma osmolality, fetal endocrine and fluid responses are prolonged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ovine fetal and adult atrial natriuretic factor metabolism.

Studies were conducted to quantify ovine fetal and adult atrial natriuretic factor (ANF) metabolism. A total of 14 pregnant ewes with singleton fetuses were prepared with vascular catheters. In protocol 1, six fetuses (mean gestation, 131 +/- 1 days) received intravenous infusions of synthetic human ANF (hANF, 100 ng.min-1.kg-1) for 60 min. Mean basal fetal plasma ANF levels increased from 180 +/- 44 pg/ml to a steady-state level of 1,233 +/- 192 pg/ml. In protocol 2, five fetuses (mean gestation, 130 +/- 1 days) received successive 40-min infusions of hANF at 5, 25, and 100 ng.min-1.kg-1. Although basal fetal plasma ANF levels (522 +/- 135 pg/ml) were greater than those observed in protocol 1, fetal plasma ANF levels increased to 1,580 +/- 295 pg/ml at the highest infusion rate. In both protocols 1 and 2, basal fetal plasma ANF levels were three- to fourfold greater than maternal levels. The fetal plasma ANF clearance rates calculated from protocol 1 and from the 25- and 100-ng.min-1.kg-1 infusions from protocol 2 were similar (89 +/- 10, 120 +/- 31, and 116 +/- 38 ml.min-1.kg-1, respectively) and were combined to yield a mean estimated fetal plasma ANF clearance rate of 102 +/- 11 ml.min-1.kg-1. In protocol 3, adult plasma ANF levels increased from 137 +/- 36 to 4,142 +/- 776 pg/ml in response to ANF infusion at 200 ng.min-1.kg-1. The mean plasma ANF clearance rate calculated for the adult animals was 59 +/- 12 ml.min-1.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Arginine vasotocin and a novel oxytocin-vasotocin-like material in plasma of human newborns.

Plasma of human adults contains an oxytocin, vasotocin-like (OT-VT) immunoreactive material that is estrogen responsive in both males and females and the levels of which are elevated during pregnancy. Although OT-VT is immunoreactive with an antiserum raised against synthetic arginine vasotocin (AVT), the elution profile of OT-VT by high-performance liquid chromatography (HPLC) is distinct from AVT, arginine vasopressin (AVP) or oxytocin (OT). Because the fetus is also exposed to high estrogen levels during pregnancy and AVT has been reported to be present in human fetal pituitaries, cord blood samples from 16 vaginally delivered human newborn infants were examined for evidence of OT-VT and AVT. Analysis of an extracted pool of cord blood plasma by HPLC revealed 4 peaks (I-IV) of AVT-like immunoreactivity. Peaks II and IV coeluted with synthetic AVP and OT, respectively, and were attributable to cross-reaction of the AVT antiserum with these peptides. Peak I was identified as AVT on the basis of its coelution with synthetic AVT. Peak III eluted in a manner identical with OT-VT. These results indicate that human newborn plasma contains at least three neurohypophysial peptides, AVP, OT and AVT. Additionally, newborn plasma contains an AVT-like immunoreactive material that is distinct from AVT, AVP and OT, but is identical with a novel OT-VT material observed in plasma of estrogen-primed adults. The physiological significance of AVT and OT-VT in newborn plasma remains to be determined.

Arginine Vasopressin↗

Ovine fetal urine contribution to amniotic and allantoic compartments.

The ovine pregnancy has been extensively studied as a model for amniotic fluid metabolism potentially serving as a model for human oligohydramnios. However, it is recognized that the ovine pregnancy contains an allantoic fluid compartment not present in human pregnancies at term. Earlier studies in sheep suggested that the fetal urine contribution to allantoic fluid diminished at term, but without an explanation for maintenance of the significant volume of the allantoic cavity. In the present study we examined the relative fetal urine excretion of 3H-inulin into the allantoic and amniotic cavities in the near-term ovine pregnancy. Amniotic and allantoic volumes, as determined by technetium-labelled dextran and chromium-tagged erythrocyte dilution, were similar although there were significant differences in composition. The allantoic fluid compartment received an equal or greater proportion of fetal urine than did the amniotic fluid during the study period. These results indicate the importance of the allantoic fluid volume and composition in the study of ovine fluid dynamics.

Allantois↗

Fetal atrial natriuretic factor and arginine vasopressin responses to hyperosmolality and hypervolemia.

Atrial natriuretic factor (ANF) is a class of diuretic and natriuretic peptides secreted by mammalian cardiac atria. Although basal plasma ANF levels in the ovine fetus are elevated relative to the adult, fetal secretion of ANF increases in response to intravascular isotonic saline infusion. Recent in vitro and in vivo studies indicate that ANF secretion also may be stimulated by increased plasma osmolality and/or sodium concentration. The present studies were conducted to determine if volume expansion associated with increased plasma osmolality would further augment ANF secretion in the ovine fetus. In response to successive 30-min intravenous infusions of 3% saline at 0.5 and 1.0 ml/kg/min fetal plasma ANF significantly increased from a basal level of 98 +/- 31 pg/ml to a peak of 439 +/- 42 pg/ml (p less than 0.05). During a 30-min postinfusion recovery period, fetal plasma ANF significantly decreased from peak values to 224 +/- 10 pg/ml (p less than 0.05), although remaining above basal levels. Fetal plasma osmolality significantly increased from 300 +/- 2 mosmol to 325 +/- 3 mosmol (p less than 0.05) whereas fetal plasma arginine vasopressin increased from 1.9 +/- 0.4 to 10.9 +/- 7.0 pg/ml (p less than 0.05) at the conclusion of the 3% saline infusion. During the saline infusion a significant increase in fetal heart rate and decrease in fetal hematocrit were noted. Fetal blood pressure and maternal plasma ANF and arginine vasopressin concentrations remained unchanged. Despite the potential stimulatory effects of hyperosmolality, increased plasma arginine vasopressin, and intravascular volume expansion, the increase in fetal plasma ANF in the present study did not exceed that induced by isotonic saline alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Atrial natriuretic peptide in the sheep.

To study atrial natriuretic peptide (ANP) physiology in the chronically catheterized pregnant sheep model we developed a heterologous radioimmunoassay for ovine ANP using an antiserum raised against 1-28 human ANP. This antiserum (Tor I) is specific for the aminoterminus of the human ANP molecule and shows little cross reaction with any carboxyterminus ANP fragments. Ovine ANP immunoreactivity was characterized using this antiserum and a commercially available carboxyterminus ANP antiserum obtained from Peninsula Laboratories. Each antiserum detected 2 peaks of immunoreactivity in ovine atrial extracts chromatographed on a Biogel P-10 column. The minor peak migrated at a position close to 125I-human ANP whereas the major peak represented a larger molecular weight species of ANP. Examination of gel filtration eluates of ovine plasma extracts showed one immunoreactive ANP peak using the Tor I assay system and 2 peaks with the Peninsula Laboratories assay. Plasma immunoreactive ANP levels were determined in 9 sheep using both radioimmunoassay systems. Mean (+/- SEM) levels were similar using the Peninsula Laboratories and the Tor I assay systems (57 +/- 8 pg/ml versus 43 +/- 4 pg/ml, P greater than 0.05). Using the Tor I antiserum, fetal plasma immunoreactive ANP levels were found to be significantly higher than maternal levels (188 +/- 17 versus 48 +/- 8 pg/ml, P less than 0.01) whereas pregnant and nonpregnant adult sheep had similar plasma immunoreactive ANP levels (48 +/- 8 versus 43 +/- 4 pg/ml, P greater than 0.05). Disappearance curves of synthetic human ANP from the plasma of maternal and fetal sheep were assessed using both immunoassay systems and found to be similar.

Animals↗

Perinatal fluid and electrolyte regulation: role of arginine vasopressin.

Not many years ago, the fetus was perceived to exert little impact on amniotic fluid homeostasis. It is now clear that the fetus plays an integral role in modulating fluid flux between the maternal, fetal, and amniotic fluid compartments. Moreover, fetal AVP secretion and the associated renal and cardiovascular responses represent important aspects of the potential to adapt to changes in the intrauterine environment. Although the physiologic significance of the increased AVP secretion observed in response to labor and delivery remain speculative, AVP regulation also is an essential aspect of neonatal adaptation. Still, many questions remain regarding both the regulation of fetal and neonatal fluid dynamics and the ontogeny of AVP receptor systems.

Animals↗

Plasma atrial natriuretic peptide response to volume expansion in the ovine fetus.

Atrial natriuretic peptide is a potent diuretic and vasorelaxant peptide secreted from the cardiac atria of adult mammals in response to increased intravascular volume. In sheep, fetal plasma levels of atrial natriuretic peptide are significantly greater than maternal levels, but the factors that control fetal release of atrial natriuretic peptide have not been defined. The present studies were conducted to determine whether the fetus responds to increased intravascular volume by atrial natriuretic peptide secretion. The mean (+/- standard error of the mean) atrial natriuretic peptide of basal fetal plasma (115 +/- 24 pg/ml) in chronically catheterized ovine fetuses (131 +/- 1 days' gestation) was significantly greater than atrial natriuretic peptide levels of basal maternal plasma (56 +/- 12 pg/ml). In response to successive 30-minute intravenous infusions of 0.9% saline solution at 0.5 and 1.0 ml/kg/min, fetal plasma atrial natriuretic peptide significantly increased to a maximum of 409 +/- 72 pg/ml during the high-dose saline infusion and returned to 234 +/- 83 pg/ml during a 30-minute recovery period. The increase in fetal plasma atrial natriuretic peptide was significantly correlated with the volume of saline solution infused (r = 0.68). During the saline infusion, a significant increase in fetal blood volume and heart rate was noted. Fetal blood pressure, maternal plasma levels of atrial natriuretic peptide, and fetal and maternal plasma osmolality remained unchanged. Despite elevated basal levels of plasma atrial natriuretic peptide, the third-trimester ovine fetus responds to increases in intravascular volume with a further increase in atrial natriuretic peptide secretion.

Animals↗

Thresholds for physiological effects of plasma catecholamines in fetal sheep.

To clarify the physiological role for the marked increases in circulating norepinephrine (NE) and epinephrine (E) that occur at birth, we performed graded infusions of NE and E in preterm (131 days) and full-term (142 days) fetal sheep. A variety of hemodynamic, metabolic, and endocrine responses to stepwise increases in plasma catecholamine levels were analyzed by computer-based graphical analysis of the dose-response curves. We determined the "threshold" value or minimum plasma concentration necessary to produce discernible effects. We observed increases in systolic blood pressure, diastolic blood pressure, and dP/dt beginning at plasma concentrations of 500-800 pg/ml of NE or E. In contrast, increases in plasma free fatty acid and glucose levels were observed at E concentrations as low as 50-100 pg/ml. Full-term animals had generally lower thresholds and higher peak responses than preterm animals. Because these thresholds for infused NE and E are well within the range of plasma catecholamine values seen at birth, these results underscore the importance of circulating catecholamines in the events of neonatal adaptation.

Animals↗

Clonidine decreases plasma and cerebrospinal fluid arginine vasopressin but not oxytocin in humans.

To evaluate the alpha 2-noradrenergic regulation of arginine vasopressin (AVP) and oxytocin (OT) in normal humans, we measured the effect of the alpha 2-agonist clonidine on concentrations of these neuropeptides in both plasma and cerebrospinal fluid (CSF). Subjects underwent two lumbar puncture studies, one of which was performed 100 min after oral administration of 5 micrograms/kg clonidine. Plasma AVP and OT were measured at a single time point 10 min before lumbar puncture. Both plasma and CSF AVP were significantly lower in the clonidine condition than in the control (no drug) condition. Neither plasma nor CSF OT differed significantly between conditions. Our data confirm previous reports of alpha 2-noradrenergic inhibition of neurohypophyseal release of AVP into blood, and extend these findings to healthy human subjects. Our data also suggest that AVP appearance in CSF, presumably from extraneurohypophyseal vasopressinergic neurons, is regulated by an inhibitory alpha 2-noradrenergic mechanism.

Adult↗

Fetal arginine vasopressin under basal and hypoosmolal conditions.

Blood samples (4 ml) for plasma arginine vasopressin (AVP) measurements were obtained at 3- to 4-hour intervals under basal conditions for 1-2 days from 5 date-bred ewes with chronic maternal and fetal vascular catheters. In addition, 6 chronically catheterized ewes were infused with 2 liters of 0.45% NaCl over 30 min. Fetal and maternal blood samples were obtained before and after the infusion period for measurement of plasma osmolality and AVP concentrations. In the first study, maternal and fetal plasma AVP levels correlated significantly (p less than 0.01, by linear regression analysis) under basal conditions. In the second study, baseline mean (+/- SEM) plasma osmolality was similar for pregnant ewes and fetuses (303 +/- 3.1 and 302 +/- 2.4 mosm/kg, respectively). There was a significant (each, p less than 0.01 by paired t test) decrease from baseline in maternal and fetal osmolality during the 30 min after completion of the hypotonic saline (to 292 +/- 4.7 and 296 +/- 2.4 mosm/kg, respectively). Fetal plasma AVP levels decreased 17 +/- 6% by 30 min following the completion of water loading (1.7 +/- 0.07 to 1.4 +/- 0.16 microU/ml; p less than 0.05). Maternal plasma AVP levels decreased 16 +/- 4% by 30 min after completion of infusion (1.6 +/- 0.14 to 1.38 +/- 0.6 microU/ml; p less than 0.05). These results indicate that maternal and fetal plasma AVP levels correlate under basal conditions and that maternal water loading, which significantly decreases fetal plasma osmolality, significantly suppresses fetal plasma AVP concentrations.

Animals↗

Epidermal growth factor acts as a corticotropin-releasing factor in chronically catheterized fetal lambs.

Epidermal growth factor (EGF) has been reported to stimulate adrenocorticotropin hormone (ACTH), growth hormone and prolactin secretion from pituitary tissue in vitro, and in large doses evokes ACTH secretion in adult sheep in vivo. In order to assess a possible role for EGF in the pituitary hyperfunction characteristic of the in utero fetus, we measured changes in plasma immunoreactive ACTH concentrations after acute administration of saline, purified mouse EGF or synthetic ovine corticotropin releasing factor (CRF) to chronically catheterized fetal sheep. Both CRF and EGF were associated with increases in plasma immunoreactive ACTH concentrations. Peak values 60 min after 10-micrograms injections of either EGF or CRF increased from baseline ACTH values of 61 +/- 11 pg/ml to 191 +/- 37 and 178 +/- 25 pg/ml, respectively. Dose-response studies indicate that at low doses (less than 20 micrograms) EGF is as potent a stimulus for ACTH release as CRF. EGF infusion was not associated with detectable changes in circulating CRF, catecholamines, arginine vasopressin levels, or plasma growth hormone concentrations. We speculate that EGF may be important in the regulation of pituitary function in the developing mammalian fetus.

Adrenocorticotropic Hormone↗