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Biomedical subjects

V R Mukku

Publications and source records attributed to V R Mukku.

33 records · Page 2Linked to original sources
PubMed1984

Regulation of epidermal growth factor receptor levels by thyroid hormone.

The binding of iodinated epidermal growth factor (125I-EGF) to membrane preparations from the livers of euthyroid and hypothyroid rats was examined to determine if thyroid hormones regulate EGF receptors. Binding in membrane preparations from hypothyroid livers was only 30-40% compared to that of euthyroid controls. Treatment of hypothyroid animals with a single dose of L-T3 96 h prior to sacrifice restored EGF binding nearly to the control levels. Scatchard analysis of the binding data indicated that the decrease in EGF binding in hypothyroid membranes was due to a decrease in the number of the receptors. Affinity labeling/cross-linking of 125I-EGF to hepatic membranes with disuccinimidyl suberate followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed a prominent band of Mr = 170,000, which was decreased in hypothyroid samples to the same extent as EGF binding. EGF-stimulated receptor kinase activity in detergent extracts of hepatic membranes also revealed a major phosphorylated protein species of Mr = 170,000, which was also decreased in samples from hypothyroid animals to approximately the same degree as EGF binding. Binding, affinity labeling/cross-linking, and phosphorylation measurements thus indicate that the levels of hepatic EGF receptor are regulated by thyroid status. These results raise the possibility that some in vivo affects of thyroid hormones may be mediated by alterations in EGF receptor levels.

Animals↗
PubMed1984

The estrogenic activity of DDT: the in vitro induction of an estrogen-inducible protein by o,p'-DDT.

Induced protein is a commonly measured marker for estrogenic action. The induction of induced protein by o,p'-DDT was studied in an in vitro system. Nuclear levels of estrogen receptor translocated by o,p'-DDT correlated highly with induced protein induction, and the time course for induced protein induction was consistent with an estrogen receptor-mediated mechanism. While the maximum amount of induced protein produced by o,p'-DDT was less than after 17 beta-estradiol exposure, the induced protein formed by each compound was indistinguishable on nondenaturing and denaturing polyacrylamide gels. Also, it was shown that o,p'-DDT does not cause additional induction of induced protein over that seen with maximum levels of 17 beta-estradiol, further supporting the premise that these compounds share a common pathway in stimulating the synthesis of induced protein.

Animals↗
PubMed1984

Hormonal control of uterine growth: alterations in luminal epithelial deoxyribonucleic acid synthesis after intraluminal application of estrogen.

Administration of a single injection of estradiol (E2) causes a maximum increase in DNA synthesis in the uterine luminal epithelium approximately 24 h later. We previously reported that animals receiving a second injection of E2 15-18 h after the first show an apparent decrease in DNA synthesis measured in this cell type at 24 h. This apparent decrease in DNA synthesis is due to a shift in the time course of DNA synthesis rather than an absolute decrease in this parameter. In this report we demonstrate that this inhibitory effect of a second injection of E2 is also observed after intraluminal instillation of the hormone. This effect is dose dependent and appears to result from a shift in the time course of luminal epithelial DNA synthesis. The intraluminal instillation of E2 produces the same pattern of nuclear receptor localization as sc administration of the hormone. These results suggest that this inhibitory effect we previously described results primarily from a direct action of E2 on the luminal epithelium.

Animals↗
PubMed1983

Evidence for thyroid hormone receptors in uterine nuclei.

Nuclear preparations from the rat uterus contain specific, high affinity binding sites for T3, with the properties expected of a thyroid hormone receptor. The Kd value for the binding of T3 to these sites is 9.3 +/- 0.1 x 10(-10) M and the maximum number of binding sites is 0.11 +/- 0.02 pmoles T3 bound per mg of DNA. Competition experiments with Triac, D-T3, T4, and rT3 compared to L-T3 revealed relative affinities of 87%, 22%, 15%, and 1.6% respectively. T3 binding sites solubilized from uterine nuclear preparations by high salt extraction sediment at 3.6 S and are destroyed largely by trypsin treatment. Estradiol treatment of ovariectomized rats for 3 days did not alter the quantity of T3 binding sites expressed on the basis of DNA content. These results suggest that uterine nuclei contain a specific T3 receptor and raise the possibility that this hormone may have direct effects on the uterus.

Animals↗
PubMed1983

Effect of ovariectomy and estrogen treatment on uterine benzylamine oxidase and monoamine oxidase type A.

The activity of monoamine oxidase type A (MAO-A) of rat uteri is known to be modulated by sex steroids but no information is available with regard to benzylamine oxidase (BzAO). Thus, uterine MAO-A and BzAO activities were assayed in ovariectomized (3 weeks) and ovariectomized plus estrogen treated rats (17 beta-estradiol, 10 micrograms/kg/day, i.p. for three days). Compared with sham operated controls, MAO-A activity (total and specific) was decreased by ovariectomy and restored partially by estrogen treatment. In contrast, BzAO activity was not influenced selectively. Total BzAO activity followed changes in uterine weight such that the specific activity of BzAO, per mg tissue, was not statistically different between the three experimental groups. Although changes in the specific activity of BzAO were found on a protein and DNA basis, these changes reflect primarily alterations in protein and DNA contents and not BzAO activity. Since BzAO appears to be insensitive to direct modulation by sex steroids and may be located predominantly in uterine blood vessels, it is speculated that the enzyme may serve as a marker for hormonal influences on the vascularity and structure of the uterine vascular bed.

Animals↗
PubMed1982

Hormonal control of uterine growth: temporal relationships between estrogen administration and deoxyribonucleic acid synthesis.

Administration of a single injection of estradiol (E2) causes a maximum increase in DNA synthesis of all major uterine cell types approximately 24 h later. Animals given a second injection of E2 6-12 h after the first show an apparent increase in DNA synthesis in the luminal epithelium. Animals receiving a second injection of E2 15-18 h after the first show an apparent decrease in DNA synthesis at 24 h, which is most prominent in the luminal epithelium. This apparent decrease in DNA synthesis is most apparent if the second injection of E2 is given 18 h after the first, and is due to a shift of 10-12 h in the time course of DNA synthesis rather than to an absolute decrease in this parameter. This shift in the time course of uterine DNA synthesis is a dose-dependent phenomenon and displays a dose-response curve similar to that for the stimulation of DNA synthesis by a single injection of E2. A third injection of E2, 28 h after the initial hormone treatment, again causes a shift of 10-12 h in the time course of DNA synthesis relative to that in animals receiving two injections of hormone. These results suggest that nuclear levels of estrogen receptor, which initially increase after hormone administration, must decrease before the onset of uterine DNA synthesis.

Animals↗
PubMed1981

Hormonal control of uterine growth: the effect of hypothyroidism on estrogen-stimulated cell division.

The increase in mitotic indices of uterine luminal epithelium, stroma, and myometrium were determined as a function of time after the administration of a single dose of 17 beta-estradiol to euthyroid and hypothyroid rats. Hypothyroidism reduced the increase in the mitotic index 5-fold in the luminal epithelium, 6-fold in the stroma, and 9-fold in the myometrium. In addition to reducing mitotic indices, hypothyroidism also produced a shift of 12 h in the time course of estrogen-stimulated cell division of all uterine cell types relative to euthyroid animals. This shift in the time course of cell division was preceded by a shift in the time course of uterine DNA synthesis measured by tritiated thymidine incorporation. In contrast, hypothyroidism did not alter the magnitude or the time course of synthesis of 2-deoxyglucose-6-phosphate from 2-deoxyglucose after estrogenic stimulation. These results indicate that hypothyroidism decreases the ability of all major uterine cell types to undergo cell division in response to acute administration of estradiol, and also shifts the time course of the uterine growth response to the hormone.

Animals↗
PubMed1981

Stimulatory and inhibitory effects of estrogen and antiestrogen on uterine cell division.

Acute administration of 17 beta-estradiol or the antiestrogen nafoxidine to immature rats produces quantitatively similar responses in the uterine stroma and myometrium, although the responses to nafoxidine occur at slightly later times. Both the hormone and drug cause nuclear translocation of equivalent amounts of estrogen receptor in these two cell types, although receptor translocation is slower with nafoxidine, and nuclear receptor levels remain elevated for an extended time. Based upon labeling and mitotic indices, however, the response of the luminal epithelium to a maximum dose of nafoxidine is much lower than that produced by estradiol, although nafoxidine treatment causes massive hypertrophy of luminal epithelial cells and causes nuclear translocation of estrogen receptors in this cell type. If nafoxidine is administered 30 min after administration of estradiol, cell division in the luminal epithelium is inhibited. Furthermore, multiple injections of estradiol itself within a 24-h period decrease cell division in the luminal epithelium relative to controls receiving a single injection of the hormone. These results indicate that estradiol and the antiestrogen can have both inhibitory and stimulatory effects on the luminal epithelium and that cell division in different uterine cell types can be differentially affected.

Animals↗
PubMed1979

Enhancement of hormonal stimulation in intact cells. Potentiation of GTP-dependent activation of adenylate cyclase.

The ability of prostaglandin E1 (PGE1) and cholera toxin to increase cyclic AMP levels is potentiated 6-fold when normal rat kidney (NRK) cells are treated with picolinic acid or histidinol, or grown in isoleucine-deficient medium. The response to (-)-isoproterenol is increased 2-fold in NRK cells treated with picolinic acid but not in cells subjected to isoleucine deprivation. The increase in agonist responsiveness is time-dependent, reaches its maximum at 40 h, and is quickly reversed following removal of picolinic acid or addition of medium with normal amounts of isoleucine. The cholera toxin response is also increased about 7-fold in simian virus 40-transformed NRK cells and Moloney sarcoma virus-transformed NRK cells treated with picolinic acid. GTP-stimulated, but not fluoride-stimulated, adenylate cyclase activities are increased in membranes from NRK cells treated with picolinic acid or starved for isoleucine, indicating that the increased response is due, at least in part, to a specific potentiation of GTP-dependent functions of the adenylate cyclase system. The results demonstrate that GTP-dependent events in hormonal stimulation of adenylate cyclase can be altered in intact cells to modulate hormonal enhancement of cyclic AMP production.

Adenylyl Cyclases↗
PubMed1979

Evidence in intact cells for an involvement of GTP in the activation of adenylate cyclase.

Treatment of cultured normal rat kidney cells with virazole or mycophenolic acid which are inhibitors of IMP dehydrogenase decreases by 50 to 70% the ability of prostaglandin E1 or isoproterenol to elevate cAMP levels. Inhibition is maximal by 2 h. The response to cholera toxin is not significantly decreased. Basal cAMP is not affected. Under these conditions, GTP is decreased by 80%, ATP is only 10 to 15% decreased, and UTP and CTP are slightly increased. Normal GTP levels and the responses to prostaglandin E1 and isoproterenol are restored if guanosine, but not inosine, is added with the inhibitor. The response to isoproterenol is recovered within 5 min after removal of mycophenolic acid. Desensitization to prostaglandin E1 or isoproterenol stimulation occurs under conditions where GTP is 80% decreased. These results in intact cells provide direct evidence for a role for GTP in the activation of adenylate cyclase and support previous conclusions from studies with cell homogenates.

Adenosine Triphosphate↗
PubMed1978

Passive immunization with an antibody to the beta-subunit of ovine luteinizing hormone as a method of early abortion--a feasibility study in monkeys (Macaca radiata).

Antiserum to the beta-subunit of ovine luteinizing hormone (oLH-beta) raised in monkeys (Macaca radiata) has been tested by a variety of criteria both in vivo and in vitro to establish its ability to neutralize oLH, hLH, and human chorionic gonadotropin (hCG). Passive administration of this antiserum caused inhibition of ovulation and termination of pregnancy in recipient monkeys as indicated by premature vaginal bleeding and a significant reduction in serum progesterone and estrogen levels. The results suggest that antiserum raised in monkeys against oLH-beta can neutralize monkey LH as well as monkey CG.

Abortion, Induced↗