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Biomedical subjects

R P Ekins

Publications and source records attributed to R P Ekins.

At least 19 recordsLinked to original sources
PubMed1992

Maternal hypothyroxinemia and brain development: I. A hypothetical control system governing fetal exposure to maternal thyroid hormones.

Maternal hypothyroxinemia consequent on endemic iodine deficiency is associated with an increased incidence of neurological disorders in the offspring. Such correlations were originally postulated as reflecting direct effects of elemental iodine on fetal brain development during early pregnancy, it being generally believed that maternal thyroid hormones do not cross the placenta in significant amount in consequence of the presence of elevated concentrations of TBG in maternal blood. However TBG possesses the capacity to enhance T4 transport to particular target organs during pregnancy. This realization led us to hypothesize a) that maternal T4 is transported to the fetus, and is of crucial importance to early fetal development, and b) that TBG forms part of a control system specifically designed to maintain at an optimal level the T4 environment to which the developing fetus is exposed. Subsequent studies in rats demonstrated that maternal T4 traverses the placenta in significant amounts prior to the development of the fetal thyroid. Other studies have led us to suggest that one or more isoforms of HCG may be implicated in a feed-back system interacting with the hypothalamic/pituitary system governing maternal thyroid hormone secretion. Though our experimental work has primarily focused on the effects of thyroid hormones on the fetal brain, we believe it to be likely that fetal exposure to maternal hormones is under placental control, and that other components of this putative system are worthy of study.

Animals↗
PubMed1992

Maternal hypothyroxinemia and brain development: II. Biochemical, metabolic and behavioural correlates.

Using a rat model, we have investigated the influence of maternal hypothyroxinemia throughout pregnancy on brain development in young and adult progeny. Although no consistent change was observed in whole brain total protein concentration, the subcellular distribution of protein was adversely affected. Isolation of glycoprotein from developing brain by concanavalin A-affinity chromatography and subsequent resolution by gel electrophoresis revealed the selective compromise of particular glycoprotein species. Furthermore, both control and experimental progeny expressed unique glycoprotein species which either persisted over the period studied or were transient. Calcineurin, a regulator of neurite elongation, was compromised in young progeny, as were a number of lysosomal enzymes (beta-D-glucosidase and aryl sulphatase). In adult progeny, the content of cerebroside sulphate (a major myelin galactolipid) was reduced in midbrain and paleocortex, and brain region-specific compromise was observed for acetylcholine metabolic enzymes. These changes were associated with alterations in behavioural output. We conclude that the availability of maternal thyroxine to the fetus may be a critical determinant for normal brain development and function.

Animals↗
PubMed1979

Correction for the presence of cross-reactants in saturation assays: application to thyroxine cross-reactivity in 3,3',5'-(reverse)-triiodothyronine radioimmunoassay.

Cross-reaction of anti-3,3',5'-triiodothyronine (rT3) antisera with thyroxine has proved problematical in the development of radioimmunoassays for rT3. Results of experimental work with two antisera with differing specificities are presented which illustrate certain aspects of cross-reacting assay systems. The mathematical theory of a single binding-site, two ligand assay is discussed and extended by use of a multiple binding-site computer model to a two binding-site, two ligand system. It is suggested that for the practical evaluation of the nature and extent of cross-reaction, a family of response curves for the hormone should be drawn, each curve representing the addition of a fixed mass of the cross-reactant to a set of standard incubation mixtures. Such curves will reveal whether the antiserum is (a) specific, implying that assay results require no correction, (b) behaves as a single binding site system, in which case measurement of the relative potency of the two ligands at the point on the response curve generated by the serum sample will enable an algebraic correction to be made, given that the T4 concentration is known or (c) behaves as a multiple binding-site system where correction necessitates the use of a nomogram.

Binding Sites, Antibody↗
PubMed1979

The association of actin with a thyroid lysosomal fraction.

A lysosome-enriched fraction was prepared from bovine thyroid tissue using sucrose gradient centrifugation. An inhibitor of DNAase I was found to co-sediment and co-purify with the lysosomal fraction. This inhibitory activity is blocked by heavy meromyosin in the absence of ATP, and a component of 42000 molecular weight can be isolated by affinity chromatography on DNAase I linked to Sepharose. These results are consistent with the presence of an actin-like protein in a lysosome-enriched preparation from bovine thyroid tissue. Also, an increase in the level of membrane-associated actin is observed in response to thyrotropin stimulation of the thyroid tissue

Actins↗
PubMed1978

Effect of TRH and dopamine on cyclic AMP levels in enriched mammotroph and thyrotroph cells.

Populations of normal anterior pituitary cells enriched in thyrotrophs or mammotrophs prepared by velocity sedimentation were used to investigate the effect of modulators of TSH and prolactin secretion on cyclic AMP accumulation. In both thyrotroph-enriched and mammotroph-enriched fractions, IBMX increased cyclic AMP accumulation. In the presence of IBMX, TRH invoked an increase in cyclic AMP suggesting that TRH modulates cyclic AMP accumulation in both of these cell types from normal pituitary glands. In the mammotroph-rich fraction, dopamine inhibited the increase in cyclic AMP induced by TRH. In contrast however, in the thyrotroph-enriched fraction dopamine lowered neither cyclic AMP concentration nor TSH secretion. Thus the inhibiting effect of dopamine on cyclic AMP appears to be specific for prolactin-secreting cells.

1-Methyl-3-isobutylxanthine↗
PubMed1978

Characterization of thyrotropin binding to specific receptors in human fat tissue.

Specific receptors for thyrotropin were found to exist in membranes from whole human subcutaneous fat tissue. The characteristics of the interaction of 125I-labelled thyrotropin with such receptors were determined and compared with the stable, high-affinity thyrotropin receptor shown previously to exist in guinea pig fat membranes. Specific binding was readily detectable using low concentrations of membranes (up to 80 microgram/ml), though specific binding was reduced at higher membrane concentrations. Increasing concentrations of unlabelled thyrotropin reduced fractional binding, revealing saturation of a population of mixed affinity sites (highest Ka of the order of 0.3 X 10(9) M-1). Little cross-reactivity was observed with other lipolytic or structurally related hormones, though some cross-reactivity was observed in the presence of human chorionic gonadotropin. Association was temperature-dependent and rapid at 37 degrees C, though prolonged incubation revealed some instability of binding at this temperature. Binding was reversible with a high dissociation rate constant, and was particularly sensitive to the presence of low concentrations of sodium or calcium ions. Using membranes prepared from isolated human fat cells, binding of thyrotropin was equally sensitive to the addition of cations.

Adipose Tissue↗
PubMed1977

Studies on the control and dynamics of thyrotropin secretion from isolated adenohypophyseal cells.

Thyrotropin (TSH) secretion from isolated anterior pituitary cells has been studied using the technique of cell column perifusion. The consistency in secretory rate and temporal profiles of TSH output in response to stimulation illustrated that the system is suitable for studying the kinetics of stimulation and inhibition of secretion. During perfusion TSH release was stimulated in response to a variety of secretogogues, namely TRH, raised potassium concentrations and phosphodiesterase inhibitors. The onset and termination of the secretory responses were rapid and displayed a temporally biphasic pattern of secretion. Dose-related increases in TSH output in response to TRH and consistent responses to repetitive pulses of TRH (5.5 X 10-10 M) during a 4 h period were demonstrated. Studies on the dynamics of thyroid hormone feedback on TRH-stimulated TSH secretion indicated that inhibition was manifest within 1 h and reached a maximum after 2 1/2 h during continual exposure to thyroid hormones. Isobutylmethylxanthine (IBMX) potentiated the effect of raised K+ as well as that of TRH on TSH secretion, suggesting an as yet unidentified relationship between Ca2+ and cyclic AMP.

Animals↗
PubMed1976

Maternal thyroid function, iodine deficiency and fetal development.

In an area of New Guinea where there is dietary iodine deficiency, measurements of thyroid function have been made on women of child-bearing age, several of whom were pregnant at the time. The outcome of these pregnancies, and also of those occurring in the four preceding years, were examined in relation to indices of thyroid function. More stillbirths, infant deaths and endemic cretins occurred among the offspring of women who showed biochemical evidence of iodine deficiency, without clinical evidence of hypothyroidism. This situation differs from that of untreated myxoedema or congenital hypothyroidism in women, which is usually associated with altered menstrual function, infertility or repeated abortion. Mechanisms that may account for these differences and the possible implications are discussed.

Child, Preschool↗