Biomedical subjects

J Lakshmanan

Publications and source records attributed to J Lakshmanan.

At least 55 records · Page 3Linked to original sources

PubMed1986

Neonatal hyperthyroidism impairs epinephrine-provoked secretion of nerve growth factor and epidermal growth factor in mouse saliva.

We examined long-term effects of neonatal hyperthyroidism on salivary secretions of nerve growth factor and epidermal growth factor in male and female mice at the age of 31 days. Hyperthyroidism was induced by thyroxine (T4) injections (0.4 microgram/g body weight/day) during days 0-6. Littermate control mice were treated with vehicle. T4 treatment did not alter the amounts of protein secreted into saliva but hormone administration induced alteration in the types of protein secreted. T4 treatment decreased the contents of both nerve growth factor and epidermal growth factor secreted into the saliva. A Sephadex G-200 column chromatographic profile revealed the presence of two distinct nerve growth factor immunoreactive peaks, while epidermal growth factor immunoreactivity predominantly eluted as a single low molecular weight form. T4 treatment did not alter the molecular nature of their secretion, but the treatment decreased their contents. These results indicate an impairment in salivary secretion of nerve growth factor and epidermal growth factor long after T4 treatment has been discontinued.

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PubMed1986

Neonatal hyperthyroidism in mice has different effects on epidermal growth factor levels in submandibular gland, urine, and blood.

We examined long-term effects of neonatal hyperthyroidism in female mice by measuring the epidermal growth factor levels in the submandibular gland, urine, and serum at the age of 31 days. Hyperthyroxinemia was induced by thyroxine injections (0.4 microgram/g/day) on days 0-6. Littermate controls received the alkaline saline vehicle. The treatment accelerated incisor eruption and eyelid opening. It also retarded growth. The elevation of plasma thyroxine concentration which normally occurs during wk 2 to reach a peak around day 15 was abolished. Submandibular gland epidermal growth factor levels on day 31 were markedly subnormal, indicating maturational delay. In contrast, epidermal growth factor levels were unaffected in urine and supranormal in serum. These differences in response suggest that the regulatory mechanisms governing epidermal growth factor levels in tissues and fluids may acquire thyroid hormone dependence at different stages.

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PubMed1986

Neonatal hyperthyroidism causes impairment in submandibular gland-nerve growth factor (SMG-NGF) ontogeny in mice.

The effect of neonatal hyperthyroidism on submandibular gland (SMG) nerve growth factor (NGF) concentrations was studied in female Swiss-Webster mice. For this purpose, newborn female pups were treated with thyroxine (T4, 0.4 microgram/g body weight/day) from birth through day 6, while their littermate pups were treated with similar volumes of vehicle. Animals were sacrificed on days 7, 15, 21, 31 and 71. Somatic growth (body weight and nose to rump length), serum T4 and T3 concentrations, and SMG and serum-NGF concentrations were measured. The data indicate that neonatal hyperthyroidism a) causes inhibition of somatic growth; b) induces alterations in normal ontogenic patterns of serum T4 and T3; c) impairs the developmental rise in SMG-NGF concentration and d) transiently increases serum-NGF levels.

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PubMed1986

Reduced urinary epidermal growth factor levels in Snell dwarf mutant mice.

Because of findings implicating thyroid and growth hormones in the regulation of urinary EGF concentration, we determined urine and kidney EGF concentrations and relative kidney weights in both sexes of 8 weeks old dwarf mutant mice of the Snell strain and their normal littermates. Both male and female dwarfs had subnormal urine and kidney EGF concentrations. A female greater than male sex difference in both concentrations was present in the normal mice, but not in the dwarfs. The male greater than female sex difference in relative kidney weight, which has been demonstrated in normal mice of the Swiss-Webster strain, was not present in the normal or dwarf Snell mice.

Aging↗

PubMed1986

Sexual dimorphism and testosterone effects on liver epidermal growth factor receptors in mice.

A sexual dimorphism (M greater than F) for liver EGF receptor binding capacity has been observed in developing mice. To assess the aetiology of this sexual dimorphism we studied the effect of exogenous testosterone administration on liver EGF receptors in adult mice. In control animals the maximal binding capacity of liver EGF receptors in females was 57% of that in males. The affinity konstant (Ka) was 1.59 X 10(9) l/mol in females compared with 3.11 X 10(9) in males. Treatment with testosterone every second day for 14 days resulted in an increase in the binding capacity with 17% in males and 80% in females making the maximal binding capacity in females equal to that in untreated males. Receptor Ka was unchanged by treatment in males, but Ka in treated females was increased to the level of males (2.96 X 10(9) l/mol). These results indicate that the sexual dimorphism of hepatic EGF receptors involves receptor affinity and capacity; both are increased by testosterone in females.

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PubMed1986

Autoimmune sympathectomy in fetal rabbits.

An autoimmune model for in utero immunosympathectomy of fetal rabbits was developed. Non-pregnant, female rabbits were injected with purified nerve growth factor and then bred after confirmation of high titers of anti-nerve growth factor antiserum. Fetuses were delivered and sacrificed at 27 and 31 days gestation and tissue norepinephrine concentration was used as an index of sympathetic innervation. There were significant reductions in tissue norepinephrine at both gestational ages. At 31 days there was a 32% reduction in lung norepinephrine concentration, 46% in the heart and 60% in brown adipose tissue. Corresponding reductions at 27 days were 68% for lung, 44% for heart and 49% for brown adipose tissue. Adrenal catecholamine content was unaffected but para-aortic gland catecholamines were slightly increased. Pulmonary beta adrenergic receptors showed a 30% up regulation in response to dennervation. Carcass weight was reduced 15% to 11% in the dennervated animals. These results demonstrate that dependence of organ sympathetic innervation on nerve growth factor can be demonstrated as early as 27 days gestation. This is a useful model to study the timing and dependence of organ sympathetic innervation on nerve growth factor and the factors which regulate this dependence.

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PubMed1985

Epidermal growth factor measurements in mouse plasma: method, ontogeny, and sex difference.

A highly sensitive mouse plasma (serum) epidermal growth factor (EGF) radioimmunoassay was utilized to determine EGF levels in mouse plasma and submandibular gland (SMG) at different ages. Plasma and serum levels were not different. Inferior vena caval blood was used because even at the age of 12 days EGF levels were markedly higher in neck blood. At 2 wk serum EGF levels were 60% of adult female levels. After a temporary decrease, mean EGF concentrations reached adult values at 31 and 60 days in the female but not yet in the male. In adults male serum EGF levels were twofold higher than female levels. This difference is parallel to but much smaller than the sex difference in SMG-EGF. SMG-EGF showed a very different ontogeny. Moreover, no correlation was present in the adults between the SMG and serum EGF concentrations. Testosterone treatment of adult females doubled their serum EGF levels, but the stimulated values were still below the mean of the male levels. The present observed plasma (serum) EGF levels in the mouse are 20-40% of previously reported values, probably because of the absence of EGF contamination from hair (urine) and milk.

Age Factors↗

PubMed1985

Epidermal growth factor binding to neonatal mouse skin explants and membrane preparations--effect of triiodothyronine.

Daily treatment of newborn Swiss-Webster mice with triiodothyronine (T3, 500 ng/day) increased epidermal growth factor (EGF) content in whole skin (epidermis + dermis). Separation of the epidermis using 0.01 M dithiothreitol followed by processing for radioimmunoassay measurement reveals levels of EGF 2-to 3-fold higher in epidermis than in whole skin. In vitro flotation of circular skin sections from control and T3 treated neonatal mice in medium containing [I125]EGF showed increased uptake of label following 5 days of in vivo T3 treatment. Mouse skin membrane preparations exhibit saturable, specific binding of [I125]EGF. T3 treatment for 5 days in vivo significantly increased EGF binding capacity in skin membrane preparations but did not alter EGF receptor affinity (Kd 4.5 nM). Protein, RNA, and DNA concentrations were significantly increased in whole neonatal mouse skin following T3 administration. These results suggest one mechanism by which thyroid hormones increase skin EGF concentration is augmentation of skin EGF receptor binding.

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PubMed1985

Epidermal growth factor in mouse ocular tissue: effects of thyroxine and exogenous epidermal growth factor.

Using a specific and sensitive epidermal growth factor (EGF) radioimmunoassay, we identified radioimmunoassayable EGF both in developing and adult mouse ocular tissues. In neonatal animals ocular EGF concentrations increase during the first 4-9 days and then decline between 9 and 15 days. Thyroxine (T4) administration (0.4 micrograms/g body weight/day from day 0) increased local EGF concentrations in eye and skin of 7-day-old neonatal mouse pups. However, this treatment did not affect submandibular gland EGF concentrations during the 1st wk of life. Both EGF and T4 are known to accelerate eye opening in the neonatal mouse. Exogenous EGF administration (2 micrograms/g body weight/day) during the first 8 days of life elicited precocious eyelid opening as expected but did not alter the serum T4 concentration, suggesting that EGF does not mediate eye opening by T4 dependent mechanism(s). Tissue EGF measurements revealed that the exogenous EGF was localized in skin and eye; however, other tissues including lung, liver, heart and submandibular gland also contained exogenous EGF. Kidney-EGF concentrations did not rise while brain-EGF levels were significantly decreased after exogenous EGF, suggesting that different EGF uptake and regulatory mechanism(s) exist in different tissues during the neonatal period. T4 administration (0.4 micrograms/g body weight/day) for 10 days to adult mice also increased ocular-EGF concentrations. However, this increase was abolished by sialoadenectomy, suggesting in contrast to the newborn, that submandibular gland is an important source of ocular-EGF in adult mice. These studies indicate that ocular EGF in the mouse is thyroxine responsive only during the neonatal period.

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PubMed1985

Urine and kidney epidermal growth factor: ontogeny and sex difference in the mouse.

We have explored the physiology of urinary epidermal growth factor (EGF) in the mouse by studying its ontogeny, and the effects of testosterone therapy on immunoreactive EGF (IR-EGF) concentrations in urine, kidney, serum and submandibular gland (SMG). Urine IR-EGF (U-EGF) increased about 100-fold relative to urea concentration and about 1000-fold relative to urine volume from the 1st day of life to adulthood. Most of this increase occurred between days 6 and 18, which is the known period of steep rise in plasma thyroid hormone concentration in the mouse. A small F greater than M sex difference was present in the adult. This difference was opposite in direction to the large M greater than F sex difference in adult SMG-EGF concentration. On day 26 (age of appearance of morphological sex difference in SMG) the sex difference was not yet present in urine, although in SMG it was even larger than in the adult. Kidney EGF concentration was low relative to U-EGF: 1 ml of adult urine contained approximately as much IR-EGF as 100 pairs of adult kidneys. In the adult, but not on day 26, there was a sex difference in kidney EGF concentration parallel to the sex difference in urine: female levels were about 30% higher than male levels. Ten days of testosterone treatment of adult female mice evoked an increase in IR-EGF concentration which was 1.7-fold for serum and 5-fold for SMG. In contrast, this treatment did not increase kidney or urine IR-EGF concentrations although kidney weight increased 1.3-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1985

Epidermal growth factor in mouse milk during early lactation: lack of dependency on submandibular glands.

Using a specific and sensitive radioimmunoassay, we found epidermal growth factor (EGF) in mouse milk during early lactation in normal and sialoadenectomized mice. Levels of EGF peaked around the 6th day postpartum and decreased thereafter up to day 12. Sephadex G-50 column chromatography of milk from normal and sialoadenectomized mice showed a single immunoreactive component comigrating with purified 6045 dalton EGF from the mouse submandibular gland. The concentrations of EGF were similar in milk collected from the breast and the stomach of the offspring immediately after feeding. The molecular profiles, concentrations, and ontogeny of EGF in milk of control and sialoadenectomized mice were also similar, suggesting that the submandibular gland is not the major source of EGF in mouse breast milk.

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PubMed1985

Nerve growth factor in mouse milk during early lactation: lack of dependency on submandibular salivary glands.

Using a specific and sensitive nerve growth factor radioimmunoassay we show measurable quantities of beta nerve growth factor in mouse milk during the period of early lactation. Partial purification by cationic exchange resin yielded a preparation which exhibited biological activity in a PC-12 cell bioassay system. Submandibular-sublingual sialoadenectomy had no influence on the breast milk NGF concentrations. These results support the presence of bioactive NGF in mouse milk during early lactation, but do not clarify the source.

Animals↗

PubMed1985

Epidermal growth factor in mouse urine: non-blood origin, and increase by sialoadenectomy and T4 therapy.

To study the origin and regulation of urinary epidermal growth factor (U-EGF), we measured EGF in adult female mouse plasma, urine and kidney tissue. We also studied the effects of excision of the submandibular salivary gland (SMG) and, after SMG excision and sham operation, 10-day therapies with T4 (0.4 microgram/g daily), testosterone propionate (TP, 12.5 micrograms/g every 48 h), and SMG extract (25 micrograms EGF daily). We measured EGF with a specific liquid phase radioimmunoassay. The mean apparent urinary clearance was 150-fold higher for EGF than for urea. U-EGF was increased 24 h after the last sc injection of SMG extract. SMG excision caused a 2.2-fold increase in U-EGF and in apparent EGF clearance. T4 brought about a 1.5 to 1.75-fold increase in U-EGF while TP was without effect. Kidney EGF (K-EGF) responded to T4 and TP like U-EGF, but SMG excision and extract were without effect on K-EGF. We conclude that 1) the immunoassayable EGF in blood plasma and SMG-EGF do not appear to be major sources of U-EGF but plasma EGF may be a minor source, 2) kidney tissue appears not to be a major source of U-EGF, 3) production of U-EGF is activated by SMG excision, 4) T4 increases both U- and K-EGF while testosterone has no effect.

Animals↗

PubMed1985

Acquisition of urine, kidney and submandibular gland epidermal growth factor responsiveness to thyroxine administration in neonatal mice.

Thyroxine (T4) administration to newborn mice on days 0-6 produced no measurable changes of submandibular gland (SMG) or kidney epidermal growth factor (EGF) concentrations on day 7, compared with vehicle-treated control pups. By contrast, this regimen caused a large increase in urine EGF levels. The effects of three T4 injection regimens (on days 0-6, 7-14 and 0-14) were then studied on day 15. The 0-14 and 7-14 day-regimens elicited large increments in urine, SMG and kidney EGF concentration, the 0-14 day-regimen having the greatest effect. The 0-6 day-regimen had no effect on SMG and kidney EGF concentrations on day 15 but did increase urine EGF. In summary, urine EGF responsiveness to T4 is present during the first week of life, but SMG and kidney EGF responsiveness develops only in the second week. Administration of T4 appears to accelerate the normal ontogeny of urine, kidney and SMG EGF.

Aging↗

PubMed1984

Structure-activity relation of thyroid hormone analogues and tissue epidermal growth factor concentrations in neonatal and adult mice.

We have shown a positive correlation between the epidermal growth factor concentration in neonatal mouse skin and prior treatment with thyroxine (T4) or triiodothyronine (T3). The results of the present study indicate similar activity of other levorotatory iodothyronine analogues and suggest the following scale of decreasing potency: T3, triiodothyroacetic acid, triiodothyropropionic acid, T4, reverse T3, and diiodothyronine. Metabolically inactive analogues (reverse T3, diiodothyronine) have no effect on skin EGF levels. A similar response pattern was observed in the adult, female mouse submandibular gland, except that T4 seemed relatively more effective.

Animals↗

PubMed1984

Acquisition of submandibular gland nerve growth factor (SMG-NGF) responsiveness to thyroxine administration in neonatal mice.

The growth of the submandibular gland (SMG) was studied in newborn mice from birth to 15 days of age. Progressive changes in wet weight were observed to accompany changes in biochemical constituents such as RNA, protein, and lipid. Thyroxine (T4) administration from days 0-6 produced changes in SMG growth and SMG accumulation of RNA, protein, and lipid components relative to control pups treated with a similar volume of vehicle. This hormone regimen produced no measurable changes in SMG nerve growth factor (SMG-NGF) concentration. T4 responsiveness also was studied from days 0-15. Three patterns of T4 injection (from days 0-6, 7-14, and 0-14) were found to elicit a differential response in the three biochemical constituents measured, but treatment from days 7-14 and 0-14 elicited precocious increments in SMG-NGF concentrations on day 15. The effect of T4 injection from birth was more effective in augmenting SMG-NGF concentration than hormone treatment initiated from days 7-14. A persistent T4 effect on SMG-NGF also was observed on day 21 following hormone treatment from days 7-14 or 0-14. In summary, the acquisition of SMG-NGF responsiveness to T4 appears to develop during the neonatal period. The administration of T4 during this period also precociously stimulates the mechanisms that govern the normal ontogeny of SMG-NGF at the time of weaning.

Age Factors↗

PubMed1984

Thyroid hormone effects on skin and hepatic epidermal growth factor concentrations in neonatal and adult mice.

Tissue concentrations of mouse epidermal growth factor (skin, submandibular gland and liver) are compared in control and thyroxine-treated neonatal and adult animals. The results identify an early onset thyroid-induced augmentation of EGF levels in neonatal skin with continuation of hormone responsiveness into adult life. Hepatic EGF levels are shown to be low and, unlike skin and submandibular gland, are not augmented by T4. The significance of hormonal modulation of nonsalivary growth factor concentrations is discussed.

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PubMed1984

Epidermal growth factor in neonatal mouse urine: maturative effect of thyroxine.

Using a specific and sensitive epidermal growth factor (EGF) radioimmunoassay, we have shown measurable quantities of EGF in mouse urine during the neonatal period. Sephadex G-50 column chromatography demonstrated the presence of a single immunoreactive component at the position defined by standard EGF (mol wt 6045). Comparison of urine urea nitrogen and urine EGF levels in neonatal and adult mice showed adult values to be 3- and 16-fold higher, respectively. Kidney weights relative to body weight were similar in newborn and adult animals while kidney EGF concentration per mg protein was 2.5-fold higher in the adult. The relative submandibular gland (SMG) weight was slightly higher in adult female mice than in the newborn, whereas SMG-EGF concentration was 15,000-fold higher in the adult than in the newborn. Thyroxine administration to neonatal mice from day 0 to day 6 increased urine EGF concentration 7-fold compared to control pups. Though the hormone treatment elicited a significant increase in relative SMG weight, its EGF concentration like that of the kidneys remained unchanged. The results suggest that urine EGF is subject to thyroid hormone modulation in newborn animals and that the changes in urine EGF concentration are independent of changes in SMG and renal EGF levels.

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