Urinary Excretion Of Epidermal Growth Factor Research Articles

Urinary excretion of epidermal growth factor and transforming growth factor-alpha in breast-fed and formula-fed infants.

Urinary epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) concentrations were determined by radioimmunoassay in a longitudinal study analyzing 348 24-h urine specimens of 32 infants (16 breast-fed, 16 formula-fed) during the first 16 weeks of life. EGF excretion showed a statistically significant increase from 6.0 +/- 2.5 to 14.1 +/- 4.9 micrograms/g creatinine (mean +/- 1 SD) during the investigation period. TGF-alpha levels were fairly constant throughout this period. Comparing breast-fed infants, with more than 100-fold higher ingestion of EGF and TGF-alpha, with formula-fed infants, no significant differences in urinary EGF and TGF-alpha excretion were observed. These results do not rule out a systemic effect of EGF and TGF-alpha after intestinal absorption in breast-fed infants. The results suggest, however, that urinary EGF and TGF-alpha originate mainly from sources other than intestinal absorption.

Trauma, especially of the submandibular glands, causes release of epidermal growth factor into bloodstream in mice

Submandibular glands in mice were traumatized by handling and then removed. Immunoreactive epidermal growth factor (EGF) in serum increased after 5 min and continued to increase, reaching at 1 h a peak of 50-fold normal in males and twice normal in females. If after traumatization the glands were repositioned with their blood supply intact, maximal increase of serum EGF at 1 h was 190-fold control values in males and 2-fold in females. In male mice, incision of abdominal wall skin led to a 15-fold increase of EGF in the serum; this rise was absent 3 days after sialoadenoectomy. After traumatization, repositioned submandibular glands lost 80% of their EGF; after the abdominal wall incision, only 30%. Following removal of submandibular glands, decrease of EGF level in serum was very slow: to 60% of the initial value after 3 days and to 40% after 10 days. By the HPLC characteristics, immunoreactive EGF in control serum and at its peak were indistinguishable. Urinary excretion of EGF was significantly elevated only when its serum level was 190-fold normal. We conclude that traumatized submandibular glands discharge into circulation a large part of their stored EGF. A similar but much less pronounced process takes place after abdominal skin incision. The presence of EGF in serum after its slow decline in sialoadenoectomized mice shows that a fraction of circulating EGF may recirculate prolonging its apparent half-life.

Depressed Urinary Excretion of Epidermal Growth Factor in Psoriasis

Epidermal growth factor (EGF) may have a modulatory role in renal growth and function. The aim of the present study was to evaluate whether urinary excretion of EGF is altered in psoriatic patients with or without arterial hypertension. The glomerular filtration rate was similar in psoriatics as compared with age- and sex-matched controls, whereas urinary EGF (microgram/g creatinine) was significantly reduced in psoriatics: normotensive subjects, 29.52 +/- 3.51 (psoriatics) versus 44.31 +/- 1.20 (controls, p less than 0.05); hypertensive subjects, 19.67 +/- 3.96 (psoriatics) versus 30.11 +/- 1.52 (controls, p less than 0.05). The urinary EGF excretion was lower in males than in females, save for hypertensive psoriatics. Urinary EGF correlated inversely with age and directly with urinary kallikrein excretion. Urinary kallikrein activity was reduced and microalbuminuria increased in hypertensive psoriatics. These alterations might suggest that initial deterioration of renal function is present in psoriasis.

Renal synthesis of epidermal growth factor is unchanged by vitamin D deficiency

In mammalian kidney, epidermal growth factor (EGF) is produced as a small internal domain of an abundant high molecular weight peptide associated with the luminal membrane of the thick ascending limb of Henle's loop and distal convoluted tubule. At present, there is no evidence to indicate a mitogenic function for the EGF-containing molecule in kidney; consideration of its molecular structure suggests the possibility of a membrane-associated physiologic role. In this study, we examine regulation of renal EGF synthesis during induction of vitamin D deficiency in mice. Despite evidence of marked hyperparathyroidism, urinary excretion of EGF was equivalent in control (2.54 +/- 0.72 micrograms/mg creatinine) and vitamin D deficient (2.13 +/- 0.97 micrograms/mg creatinine) animals. Similarly, EGF mRNA levels in kidney were comparable in the two groups. These data indicate that parathyroid hormone has no effect on renal EGF regulation, although it is known to stimulate calcium reabsorption in distal nephron segments.

Epidermal growth factor in serum, urine, submandibular glands and kidneys of diabetic mice

Levels of epidermal growth factor (EGF) in serum were significantly decreased in streptozotocin (STZ)-diabetic mice (446±168 pg/ml) after 1 week and 423±52 after 4 weeks vs 766±162 pg/ml in controls, P.002 and < .001. respectively) and in genetically diabetic ob/ob mice (455±285 vs 962±453 pg/ml in nondiabetic ob/+ controls, P.043). The urinary excretion of EGF was significantly increased in STZ mice (104±53 vs 51±23 ng/h, P.013) but unchanged in ob/ob mice (33±9 vs 45±16 ng/h, P.134). However, when expressed per mg creatinine it was decreased in both cases: in STZ mice to 680±250 ng/mg at 1 week and 684±211 at 4 weeks vs 1250±303 ng/mg in controls (P<.01); and in the ob/ob mice to 552±117 vs 1237±300 ng/mg in ob/+ controls (P<.01). EGF content of the submandibular glands of STZ mice remained unchanged at 1 week (13.1±2.9 vs 11.0±1.8 μg/mg protein, P. 170) but dropped by 4 weeks (4.7±1.2 μg/mg, P<.001); in the ob/ob mice it was less than 20% that of controls (2.1±0.8 vs 12.2±3.6 μg/mg protein). In kidneys, the EGF content was not altered in either ob/ob (524±50 vs 571±33 pg/mg protein) or STZ mice (652±183 vs 665±80 pg/mg). The preproEGF mRNA level in STZ-treated mice was reduced after 4 weeks in submandibular glands but not in kidneys. The results show that diabetes affects EGF production, utilization and/or excretion in mice and that kidneys are spared from suppressionof EGF synthesis that is pronounced in the submandibular glands.

Effect of salivarectomy on the growth of gastrointestinal mucosa and urinary secretion of epidermal growth factor in rats

The effect of salivary epidermal growth factor (EGF) on the growth and metabolism of gastrointestinal mucosa was examined by comparing DNA synthesis, DNA and RNA content, and weight of mucosa of salivarectomized and sham operated male rats. DNA synthesis of gastric mucosa was suppressed at 2 days after salivarectomy. Both weight and DNA content of oxyntic mucosa in the salivarectomized group were significantly lower than that of the sham operated group. Although salivarectomy suppressed DNA synthesis of jejunal mucosa, the difference was not significant statistically. The effect of salivarectomy on colonic mucosa was least in the gastrointestinal tract. Such a result suggested that the gradient-oriented antitrophic effect was brought about by salivarectomy. Urinary EGF excretion after salivarectomy was examined by radioreceptor assay. Although the antitrophic effect of salivarectomy on oxyntic mucosa was highest on day 2, no significant difference of urinary EGF concentration was detected on day 2. From these results it is suggested that the effect of salivarectomy on the gastrointestinal tract was not due to the change of EGF in systemic circulation but due to the change of luminal EGF.

Reduced renal prepro-epidermal growth factor mRNA and decreased EGF excretion in ARF

Levels of prepro epidermal growth factor (EGF) mRNA in renal cortical tissue and urinary EGF excretion have been determined during cisplatin and ischemia-induced acute renal failure in the rat. Northern analysis of polyadenylated RNAs of kidney cortical tissue showed diminished renal preproEGF mRNA in rats injected with cisplatin (5 mg/kg). The decrease in preproEGF mRNA occurred as early as 12 hours in the kidney and persisted for at least three days after cisplatin injection. The submandibular gland, a major site of EGF synthesis, contained normal levels of preproEGF mRNA. Transplatin, a non-nephrotoxic isomer of cisplatin, did not reduce renal preproEGF mRNA levels. Northern analysis of polyadenylated RNAs of kidney cortical tissue 24 hours after a 50 minute period of renal pedicle clamping also showed reduced preproEGF mRNA levels. By contrast, cisplatin increased renal c-fos mRNA. Urinary EGF excretion was also reduced after cisplatin and ischemia and the decrease in EGF excretion correlated significantly with the degree of renal failure. The data show that nephrotoxic and ischemic renal cell injury reduces preproEGF mRNA and urinary EGF excretion. Reduced preproEGF mRNA and diminished EGF excretion may be important in the functional and regenerative responses to renal injury.

The Effect of Growth Hormone on Urinary Epidermal Growth Factor Excretion in Growth Hormone Deficient Children

Article The Effect of Growth Hormone on Urinary Epidermal Growth Factor Excretion in Growth Hormone Deficient Children was published on July 1, 1989 in the journal Journal of Pediatric Endocrinology and Metabolism (volume 3, issue 3).

Human urinary epidermal growth factor excretion: age, sex, and race dependence.

We measured the urinary excretion of immunoreactive epidermal growth factor (IR-EGF) in random urine specimens obtained from 358 ambulatory patients and normal subjects, aged 18-90 yr, with a homologous EGF RIA. We also measured IR-EGF excretion in 24-h urine collections from 40 additional normal subjects, aged either 20-29 or 60-69 yr, to detect possible artifacts introduced in the analysis of random urine specimens by the age-related decline in the glomerular filtration rate. Urinary IR-EGF excretion decreased in a linear fashion with increasing age. Women excreted more IR-EGF than men, and whites excreted more IR-EGF than blacks of the same age and sex, but the rate of decline with increasing age was similar for all groups. These findings may provide additional insight into the role of EGF in human renal physiology.

Urinary epidermal growth factor excretion and breast cancer risk

The amount of urinary epidermal growth factor (EGF) excreted was determined in 350 normal women of whom 37 subsequently developed breast cancer. These were a group of women selected on a case-control basis from 5000 volunteers who had participated in a prospective epidemiological study. Urinary EGF excretion was not correlated with known risk factors such as age at menarche or menopause, age at first or last full-term child or parity. Neither was it associated with day or length of menstrual cycle, breast mammographic parenchymal pattern or the blood concentration of prolactin, dehydroepiandrosterone or its sulphate ester. Univariate analysis indicated that the amount of urinary EGF was significantly correlated with urinary creatinine ( P < 0.001), age ( P < 0.001), urinary androsterone ( P < 0.02) or aetiocholanolone ( P < 0.02), height ( P < 0.05) and weight ( P < 0.05). However, multivariate analysis showed that the amount of urinary EGF was correlated only with creatinine excretion ( P < 0.001) and age ( P < 0.001) and that the significance of the other correlations were probably due to the confounding influence of creatinine.

ROLE OF GROWTH HORMONE ON PLASMA EPIDERMAL GROWTH FACTOR CONCENTRATIONS

Epidermal growth factor (EGF) is known to accelerate proliferation and differentiation of multiple cell types. We previously reported that growth hormone deficient (GHD) children have decreased urinary EGF excretion compared to normal children and the excretion of EGF increases with growth hormone (GH) administration. We developed a heterologous, double antibody radioimmunoassay (RIA) based on mEGF to estimate plasma concentrations of EGF in humans. The detection limit of the assay was 0.10 ng/ml. Using this method, mean concentration of EGF in plasma from adults was 4.8±1.7 ng/ml and the mean concentration in normal children was 8.4±0.3 ng/ml. Plasma and urinary EGF in GHD children before and during treatment (0.08 U GH/kg t.i.w.) are shown in the table below: These data suggest that the plasma concentrations of EGF do not change with GH treatment of GHD children despite increases in urinary excretion. We conclude that the increased urinary excretion of EGF could reflect increased urinary clearance of this factor rather than increased production.

INCREASED EPIDERMAL GROWTH FACTOR CONCENTRATIONS IN DONAHUE'S SYNDROME (LEPRECHAUNISM)

Epidermal growth factor (EGF) is a well characterized polypeptide factor known to be important in growth and proliferation of multiple cell types. We have described a patient (Lep Ark I) with Donahue's syndrome whose phenotypic characteristics, i.e., severe acanthosis nigricans, hirsutism, pachyderma, precocious development of teeth and breast buds, and gut hypertrophy are consistent with hypersecretion or hyperfunction of epidermal growth factor. We previously demonstrated that this patient has increased secretion of epidermal growth factor in her urine (151.9±59.4 ug EGF/gm cr compared to 26.7±4.3 ug/gm in control children) but were unable to quantify plasma concentrations at that time. We have now developed a heterologus, double antibody radioimmunoassay (RIA) based on mEGF to estimate plasma levels of EGF in human plasma. Dilutions of the patient's plasma displace 125I-EGF in a linear fashion producing a line parallel to that of the EGF standards. Mean plasma concentration levels of EGF in normal adults by this method are 4.8±1.7 (N=5) and in children 8.4±0.3 (N=5). In contrast, the mean plasma concentration of EGF in Lep Ark I is 20.2±3.3 ng/ml (N=4). Reported blood levels of EGF in humans have ranged from 273±46 pg/ml to 1.89±0.5 ng/ml. Our mean plasma concentrations for children were higher than those previously reported but were less than half the value found in Lep Ark-I. We conclude that the elevated urinary excretion of EGF in Lep Ark-I reflects hyper-secretion in this patient, thus providing a disease state for this important growth factor.

Urinary excretion of epidermal growth factor in the newborn

Urinary epidermal growth factor (EGF) excretion was studied serially in 36 newborn infants, from 26 to 40 weeks gestation, from birth to three months of age. All infants excreted EGF from birth. Excretion was significantly higher in term infants than in preterm infants at birth; in term infants excretion rose steadily in early infancy and there was a similar but delayed rise in EGF excretion by preterm infants. Urinary EGF excretion appears to be related to age from conception and birth does not influence it. There was no correlation between urinary EGF excretion and the rapid maturation of the lungs and skin which occurs in preterm infants in the early neonatal period.

Epidermal growth factor in human urine from birth to puberty.

The highest concentrations of epidermal growth factor (EGF) are found in urine, but the physiological role of urinary EGF is unknown. We studied human urinary EGF excretion, by measuring its concentration with a specific homologous RIA, in 265 healthy children from birth until age 16 yr. The absolute concentrations varied widely between individuals. Mean values were approximately 10 ng/ml in 1- to 30-day-old infants; 2.5-fold higher values were found in infants aged 2 to 12 months. During the second year there was a further rise to about 70 ng/ml, and urinary EGF excretion was in the same range in older subjects. The EGF/creatinine concentration ratio was less variable. The mean ratio increased 6-fold from birth to the second year of life. Thereafter, the EGF/creatinine ratio decreased gradually to one-third of the peak level at puberty. No sex difference was found.

1283 ROLE OF EPIDERMAL GROWTH FACTOR IN THE PHENOTYPIC EXPRESSION OF LEPRECHAUNISM

Epidermal growth factor (EGF) is a polypeptide hormone important in growth and differentiation of multiple cell types. It has a wide range of biological activities including precocious eruption of teeth, gut mucosa hyperplasia, and proliferation of epidermal cells in mice. Despite multiple known biological functions and presence in several body fluids, no disease state has been identified in which there is either a deficiency or excess of EGF. Leprechaunism (L) has many of the characteristics expected in EGF hypersecretion, i.e., severe acanthosis nigricans, hirsutism, pachyderma, precocious breast development and hypertrophy of gut and genitals. We have measured urinary EGF excretion in an 8-year-old patient with L over several years and found a mean concentration to be 151.9±50.4μg/gm cr. In comparison we have measured urinary EGF concentrations in normal children and children with various disease states. EGF excretion was linear with creatinine excretion and not influenced by age. The mean EGF excretion is 26.7±4.3μg/gm cr in control children as compared to 29.6±1.1 and 39.8±1.6μg/gm cr in normal adult males and females respectively. Blood EGF levels in our patient were increased above normal. Measurement of other gut hormones were normal. We conclude that many of the phenotypic manifestations of L are secondary to excessive EGF, thus providing a disease for this well characterized but otherwise orphan hormone.

Epidermal Growth Factor (EGF) in normal children, children with constitutional short stature, and children with growth hormone deficiency

Urinary EGF was measured using a human placental membrane radioreceptor assay. This assay does not cross-react with insulin growth factor I (IGF I), somatomedin A, fibroblast, or nerve growth factors. Urinary excretion of EGF was measured in normal children (NL), in children with constitutional short stature (Con SS), untreated growth hormone deficient children (GH defic), and in growth hormone deficient children after growth hormone therapy (GH defic post Rx). EGF excretion did not differ in NL, GH defic post Rx, or Con SS children. However, it was significantly less in GH defic compared to GH defic post Rx (p<.02), NL (p<.05), and Con SS (p<.02) children. Our finding of diminished EGF excretion in untreated hGH deficiency and an EGF response to hGH therapy is the first demonstration of an alteration in EGF in association with a pathologic disorder in the human. We speculate that EGF may be implicated in hGH biologic activity.