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Biomedical subjects

L Myatt

Publications and source records attributed to L Myatt.

At least 19 recordsLinked to original sources
PubMed1992

Changes in annexin (lipocortin) content in human amnion and chorion at parturition.

Arachidonic acid is mobilized from fetal membrane phospholipids at parturition leading to increased production of oxytocic prostaglandins which may initiate or maintain myometrial contractions. Phospholipid mobilization requires activation of phospholipase A2 or C, both of which require calcium for activity. The annexins (lipocortins) are a superfamily of proteins which bind to calcium and phospholipids and thereby may alter phospholipase activity through two mechanisms: modulation of intracellular free Ca2+ concentrations or regulation of the accessibility of phospholipids to hydrolyzing enzymes. Using Western immunoblotting with monospecific polyclonal antibodies, annexins I-VI were identified in human amnion and chorion/decidua at term in tissues obtained from patients in labor or not in labor. Each annexin was present in two distinct pools: a pool which only associated with the membrane in the presence of calcium (calcium-dependent pool) and a calcium-independent pool that remained membrane bound in the presence of calcium chelators. Annexin I was present as two species, resolving at 36 kDa and 68 kDa. The total concentration of annexin I in both amnion and chorion/decidua was significantly decreased with labor, while the total concentration of annexin V in chorion significantly increased with labor. The size of individual pools of annexins also changed with labor: the calcium-dependent pool of annexins I and II in both amnion and chorion significantly decreased; the calcium-dependent pool of annexin V increased in chorion; and calcium-independent pools of annexin I in amnion and annexins I, II, and V in chorion significantly decreased with labor. The decrease in total annexin I concentration with labor in amnion reflects a substantial decrease (80-90%) in the pool tightly bound to the membrane in a calcium-independent manner. This striking change distinguishes annexin I as a potential candidate inhibitor which is specifically downregulated at parturition, potentially leading to increased access of phospholipases to substrate phospholipids and increased prostaglandin production at labor.

Amnion↗
PubMed1992

The comparative effects of big endothelin-1, endothelin-1, and endothelin-3 in the human fetal-placental circulation.

OBJECTIVE: This study compared the effects of big endothelin-1, endothelin-1, and endothelin-3 and whether endothelin-converting enzyme was present in the human fetal-placental circulation. STUDY DESIGN: Single cotyledons of term placentas were dually perfused in vitro, and increases in fetal-placental perfusion pressure to bolus injections of big endothelin-1, endothelin-1, and endothelin-3 (8 x 10(-10) to 1 x 10(-7) mol/L) were recorded. Responses to big endothelin-1 (10(-7) mol/L) were measured in the same placenta before and after perfusion of the fetal-placental circulation with the neutral metalloprotease inhibitor phosphoramidon (10(-5) mol/L), which acts as an endothelin-converting enzyme inhibitor. All experiments were performed in at least five separate placentas. RESULTS: Significant concentration-dependent increases in fetal-placental perfusion pressure were seen with endothelin-1 (p < 0.0005), endothelin-3 (p < 0.0256), and big endothelin-1 (p < 0.0034, analysis of variance). Big endothelin-1 always elicited transient vasodilatation before constriction. Phosphoramidon significantly inhibited the vasoconstrictor effect of big endothelin-1 (p < 0.039, paired t test). CONCLUSION: The three endothelins tested are vasoconstrictors, and endothelin-converting enzyme is present in the fetal-placental circulation.

Blood Circulation↗
PubMed1992

Decrease in annexin I messenger ribonucleic acid expression in human amnion with labor.

OBJECTIVE: Annexins are a superfamily of proteins that are thought to inhibit phospholipase A2 activity and hence inhibit prostaglandin production. The purpose of this study was to test the hypothesis that annexin I concentration in human amnion is reduced with labor and that this reduction is mediated by a decrease in annexin I messenger ribonucleic acid expression. STUDY DESIGN: Amnion and choriodecidua were collected from term singleton pregnancies, eight after spontaneous vaginal delivery and eight from elective cesarean section without labor. Annexin I protein was quantitated by Western blotting. Ribonucleic acid was isolated from amnion, and then annexin I messenger ribonucleic acid was identified by Northern hybridization and quantitated by slot blotting. RESULTS: Annexin I (35 kd) was identified in amnion tissue. The concentration in the group undergoing labor (320 +/- 45 integrated optical density units, mean +/- SE) was significantly reduced (p < 0.05) compared with that in the group not undergoing labor (635 +/- 65 units). The size of the annexin I messenger ribonucleic acid was approximately 1.8 kb. The mean integrated optical density for the labor group (840 +/- 139 units, mean +/- SE) was significantly reduced (p < 0.05) compared with that of the nonlabor group (1912 +/- 464 units). CONCLUSION: There is a significant decrease in annexin I messenger ribonucleic acid expression in human amnion with labor, corresponding to a significant decrease in annexin I protein concentration. This may contribute to the increased phospholipase A2 activity, arachidonic acid mobilization, and prostaglandin production at labor in humans.

Amnion↗
PubMed1992

Attenuation of the vasoconstrictor effects of thromboxane and endothelin by nitric oxide in the human fetal-placental circulation.

OBJECTIVE: We hypothesized that the endothelial-derived relaxing factor nitric oxide may contribute to low resting vascular tone and may attenuate vasoconstrictor action in the human fetal-placental circulation. STUDY DESIGN: Isolated human placental cotyledons were dually perfused in vitro, and the effects of N-monomethyl-L-arginine and N-nitro-L-arginine (3 x 10(-4) mol/L), which are nonmetabolizable analogs of L-arginine, the substrate for nitric oxide synthase, on resting perfusion pressure and on the fetal-placental circulation preconstricted with U46619 (10(-8) mol/L) or endothelin-1 (10(-8) mol/L) were established. Responses before and after inhibition were compared by paired t test. The effects of glyceryl trinitrate (10(-6) mol/L), acetylcholine (10(-4) mol/L), the calcium ionophore A23187 (10(-6) mol/L), and histamine (10(-8) to 10(-4) mol/L) were also determined in the preconstricted fetal-placental circulation. RESULTS: Both N-monomethyl-L-arginine and N-nitro-L-arginine (3 x 10(-4) mol/L) increased resting perfusion pressure (p less than 0.06), and N-nitro-L-arginine promptly and significantly increased perfusion pressure in the fetal-placental circulation preconstricted with U46619 (p less than 0.0004) or endothelin-1 (p less than 0.06). Nitric oxide generated by addition of glyceryl trinitrate (10(-6) mol/L) attenuated the vasoconstrictor effects of U46619 (p less than 0.026) or endothelin-1 (p less than 0.01). Neither acetylcholine nor the calcium ionophore A23187 had an effect on the fetal-placental circulation, whereas bradykinin further increased perfusion pressure. Histamine only relaxed the preconstricted preparations at concentrations (10(-6) to 10(-4) mol/L) above those shown to release nitric oxide in other systems. CONCLUSION: The stimulus to nitric oxide generation in the fetal-placental circulation may be hydrodynamic. Nitric oxide appears to contribute to maintenance of basal vascular tone and to attenuate the actions of vasoconstrictors in this circulation.

Acetylcholine↗
PubMed1992

Endothelin transfer and endothelin effects on water transfer in human fetal membranes.

Although endothelin-1 is synthesized by human amnion, its physiologic role and its ability to be transferred to myometrium for oxytocic action remain unclear. We investigated the transfer of endothelin-1 itself and the effects of endothelin-1 on the transfer of tritiated water across human amnion or amnion/chorion/decidua in vitro with an Ussing chamber technique. Permeability coefficients (mean +/- standard error) for 3H2O across amnion/chorion/decidua in the fetal to maternal direction were 1.26 +/- 0.21 and 1.25 +/- 0.10 x 10(-4) cm/second (N = 6) and in the maternal to fetal direction 0.90 +/- 0.07 and 0.98 +/- 0.15 x 10(-4) cm/second (N = 5) in the absence or presence, respectively, of 10(-9) mol/L endothelin-1 in the fetal reservoir. Comparable values were found in either direction with 10(-9) mol/L endothelin-1 in the maternal reservoir. Apparent permeability coefficients for 125I endothelin-1 in the fetal to maternal direction were 3.34 +/- 0.79 and 2.43 +/- 0.68 x 10(-5) cm/second (N = 5) for amnion or amnion/chorion/decidua. However, appreciable trapping of 125I endothelin-1 by the fetal membranes was apparent. Endothelin-1 does not appear to affect water movement across the human fetal membranes, and only a small proportion of endothelin-1 itself is transferred across the membranes.

Biological Transport↗
PubMed1992

Human retinal vascular cells differ from umbilical cells in synthetic functions and their response to glucose.

Cell culture systems have commonly been used to study mechanisms implicated in the pathogenesis of diabetic retinopathy, but the great majority of cell preparations used have been either of nonhuman retinal origin or nonretinal human origin. Because of questions of species and organ specificity in the function of cells of vascular origin, in this study, cultured microvascular endothelial cells (HREC), pericytes (HRPC), and pigment epithelial cells from the postmortem human retina, and endothelial cells from human umbilical vein (HUVEC) were evaluated with respect to cell proliferation, and secretory products potentially important in diabetic retinopathy, i.e., prostaglandins (PG) and plasminogen activators (PA), normalized to DNA content/well, under both basal (5 mM) and high (25 mM) glucose conditions. Glucose (25 mM) reduced DNA content similarly in both types of endothelial cells, had a lesser effect on HRPC, and did not significantly alter the proliferation of pigment epithelial cells. Basal secretion of PGI2 (measured as 6-keto-PGF1 alpha) was in the order HRPC much greater than HREC greater than HUVEC, whereas PGE2 secretion was in the order HREC much greater than HRPC greater than HUVEC. Glucose (25 mM) stimulated PGI2 secretion by HRPC, but not by either type of endothelial cell, and enhanced PGE2 secretion by HREC, but not by HUVEC or HRPC. Release of plasminogen activator activity differed between HUVEC and HREC under basal conditions and addition of 25 mM glucose stimulated release only from HREC. Glucose (25 mM) stimulated PA secretion by HREC, but not by HUVEC. These findings provide evidence that human retinal pericytes are an important source of prostacyclin, and that there are differences between HREC and HUVEC with respect to secretory functions and their modulation by glucose, indicating regional specificity of these functions. Extrapolation to human retinal vascular cells from experiments using cells from heterologous vascular beds to draw inferences about the pathophysiology of diabetic retinopathy are not valid for these cellular functions.

Adult↗
PubMed1991

Endothelin-1-induced vasoconstriction is not mediated by thromboxane release and action in the human fetal-placental circulation.

The vasoconstrictor peptide endothelin-1 (8 x 10(-10) to 1 x 10(-8) mol/L) significantly increased fetal-placental perfusion pressure in vitro in a cumulative manner from 30 +/- 2 to 123 +/- 25 mm Hg (mean +/- SEM, n = 5, p less than 0.0005, analysis of variance). Accompanying this vasoconstriction was a corresponding reduction in fetal-placental perfusate flow rate. Measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in the fetal-placental perfusate revealed a significant reduction in their release (p less than 0.0096 and p less than 0.0004, analysis of variance, respectively) when corrected for flow rate. Neither the thromboxane synthesis inhibitor dazoxiben (10(-6) mol/L) nor the thromboxane receptor antagonist SQ29548 (10(-6) mol/L) was able to block the vasoconstrictor actions of endothelin-1. Therefore endothelin-1-induced vasoconstriction in the human fetal-placental circulation does not appear to be mediated by thromboxane release or action. The stimulus to eicosanoid release in the fetal-placental circulation may be hydrodynamic, i.e., flow or shear stress.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Transfer of aspirin across the perfused human placental cotyledon.

Pregnancy-induced hypertension is associated with a reduction in prostacyclin synthesis that is relative to normotensive pregnancy, whereas thromboxane A2 synthesis is unchanged or increased. The net effect is a decreased prostacyclin/thromboxane ratio that may result in the reduced fetal-placental blood flow seen in pregnancy-induced hypertension because thromboxane is known to constrict this circulation. Low-dose aspirin (acetylsalicylic acid), which is used to treat pregnancy-induced hypertension, selectively inhibits thromboxane synthesis and therefore may alter fetal-placental blood flow. We have investigated the transfer of acetylsalicylic acid in the perfused human placental cotyledon and its effects on fetal-placental perfusion pressure. Human placental cotyledons were perfused with tissue culture medium 199 plus 5% polyvinylpyrrolidone that was gassed with 95% oxygen/5% carbon dioxide at flow rates of 10 ml/min (maternal) and 4 ml/min (fetal). Acetylsalicylic acid (10(-5) mol/L) was added to the maternal circuit, and cotyledons were perfused for 1 hour with aliquots taken from a closed fetal circuit every 5 minutes. Acetylsalicylic acid was assayed by spectrofluorometry at 306/412 nm. Our data indicate an initial rapid transfer of acetylsalicylic acid during the first 5 minutes into the fetal-placental circulation, the concentration then decreased to a steady state at 0.4 x 10(-5) mol/L. Resting perfusion pressure of both maternal and fetal circulation did not change after the addition of acetylsalicylic acid to maternal perfusate and transfer to the fetal circulation.

Aspirin↗
PubMed1991

The action of nitric oxide in the perfused human fetal-placental circulation.

Nitric oxide is thought to be the endogenous endothelium-derived relaxing factor. We investigated the effects of compounds that either generate nitric oxide intracellularly or inhibit its action on the vasculature of the human placental villus. Addition to perfusion medium of methylene blue (10(5) mol/L), which is an inhibitor of activation of guanylate cyclase by nitric oxide, significantly increased perfusion pressure of the fetal-placental circulation over a range of flow rates (1 to 10 ml/min) compared with the perfusion pressures seen in the absence of methylene blue. This suggests basal release of nitric oxide may contribute to maintenance of resting vascular tone. Both glyceryl trinitrate (10(-9) to 5 x 10(6) mol/L) and S-nitroso-N-acetylpenicillamine (10(-8) to 10(-4) mol/L), which generate nitric oxide intracellularly, were able to significantly vasodilate the fetal-placental circulation preconstricted with the thromboxane mimetic U46619 (1 to 5 x 10(-8) mol/L) in a concentration-dependent manner. These compounds had no effect in the absence of the vasoconstrictor. Thus it appears that the placental villus tree has the ability to both generate and respond to nitric oxide.

Blood Flow Velocity↗
PubMed1990

Mechanisms of parturition: the transfer of prostaglandin E2 and 5-hydroxyeicosatetraenoic acid across fetal membranes.

Prostaglandin E2 production by amnion is thought to be an important event in the onset of human labor. It has been suggested that 5-hydroxyeicosatetraenoic acid, also produced in the amnion, may mediate prelabor contractions. For either of these compounds to play a paracrine role they need to cross the chorion, which has a high capacity to metabolize prostaglandins. With the use of an in vitro system we have shown that both prostaglandin E2 and 5-hydroxyeicosatetraenoic acid cross either amnion or intact amnion-chorion-decidua at a rate similar to that of an extracellular marker sucrose. Analysis by high performance liquid chromatography revealed that at physiologic concentrations neither prostaglandin E2 nor 5-hydroxyeicosatetraenoic acid were metabolized by amnion alone. Moreover, 100% of the 5-hydroxyeicosatetraenoic acid and 72% of the prostaglandin E2 remained in the active form after passage across intact amnion-chorion-decidua. There did not appear to be any difference in the rate of transfer or permeability of the membranes before or after spontaneous labor. We conclude that both 5-hydroxyeicosatetraenoic acid and prostaglandin E2 synthesised in the amnion can cross the membranes by diffusion through the extracellular space, remaining largely unmetabolized, and may play a role in the onset of human labor.

Biological Transport↗
PubMed1990

Production of prostaglandin E2 by human amnion in vitro in response to addition of media conditioned by microorganisms associated with chorioamnionitis and preterm labor.

To examine the potential role of bacterial infection in the cause of spontaneous preterm labor, human amnion cells in tissue culture were exposed to medium conditioned by culturing each of 21 microorganisms previously found in association with chorioamnionitis and preterm labor. At a final concentration of 0.1% bacterial conditioned medium, a significant stimulation of prostaglandin E2 production from amnion cells was observed for this range of microorganisms. Conditioned medium obtained from culturing Bacteroides fragilis caused a dose-related increase in prostaglandin production, final concentrations of 0.02% to 0.1% being stimulatory but greater concentrations (0.1% to 10%) causing a progressive inhibition of prostaglandin synthesis. A similar concentration-related response in which stimulation was followed by inhibition occurred on addition of increasing concentrations of phospholipase A2 to amnion cells. These data suggest that bacterial phospholipase may release arachidonic acid from amnion leading to prostaglandin E2 synthesis, but excessive addition of phospholipase and consequent increased arachidonic acid availability may give rise to substrate inhibition of cyclooxygenase enzyme and inhibit prostaglandin E2 synthesis. Overall it appears that a wide variety of microorganisms associated with preterm labor may secrete phospholipase, which liberates amnion arachidonic acid for conversion to the oxytocic agent prostaglandin E2.

Amnion↗
PubMed1990

Regulation of prostaglandin E2 synthesis in human amnion by protein kinase C.

A role for protein kinase C (PKC) in mediation of prostaglandin E2 synthesis in human amnion cells has been suggested. We have investigated the specificity of the stimulation of PGE2 synthesis by phorbol esters and employed putative PKC inhibitors to demonstrate the specificity of PKC stimulation. The three phorbol esters, tetradecanoyl phorbol-13-acetate, phorbol-12,13-dibutyrate and phorbol-12,13-didecanoate gave concentration-dependent (10(-10)-10(-7)M) increases in PGE2 synthesis when added to amnion cells in monolayer, however, no effect was seen with the structurally similar phorbols phorbol-12-13-diacetate, 4 alpha phorbol-12-13-didecanoate or phorbol base. The stimulatory effect of TPA (10(-8)M) on amnion PGE2 synthesis could be prevented by coincubation with the putative protein kinase C inhibitors 1-(5-isoquinoline sulphonyl) piperazine, 1-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine, sphingosine and chlopromazine at concentrations of 10(-6)-10(-4)M. Addition of the transcription inhibitor actinomycin D at 10(-6)-10(-5)M prevented TPA (10(-8)M)-induced PGE2 synthesis. However, paradoxically, a further increase in PGE2 synthesis was seen when 10(-9)-10(-7)M actinomycin D was added together with TPA. The phospholipase A2 inhibitor quinacrine was able to prevent the TPA-induced increase in PGE2 synthesis even in the presence of exogenous arachidonic acid suggesting that phospholipase A2 may be a target for PKC action.

Amnion↗
PubMed1990

Pathways of arachidonic acid metabolism in human amnion cells at term.

We have compared the metabolism of (3H) arachidonic acid by monolayers of human amnion, cells obtained prior to or following labor at term. Radiolabel was either added exogenously or previously incorporated into cellular phospholipid pools to compare metabolism of arachidonic acid from different substrate sources. Cells obtained both prior to and following labor synthesized metabolites co-chromatographing on HPLC with di- and mono-HETEs and also a metabolite with polarity corresponding to a epoxyeicosatrienoic acid. Both types of cells were able to synthesize PGE2 when (3H) arachidonic acid was added exogenously. However, only those cells obtained following labor synthesized PGE2 from (3H) arachidonic acid incorporated into intracellular pools. These findings suggest that the cyclooxygenase and PGE2 isomerase enzymes are present in amnion prior to delivery but that exogenous arachidonic acid would be required for PGE2 synthesis at that time as the enzymes do not appear to be linked to a source of endogenous arachidonic acid. At the time of parturition, there may be a switching on of an enzyme system to generate arachidonic acid from intracellular pools specifically for PGE2 synthesis or alternatively coupling of such a system to a cyclooxygenase-PGE2 isomerase system resulting in PGE2 synthesis. These findings raise intriguing new possibilities for the regulation of eicosanoid synthesis in amnion which may include membrane topography, substrate pool-enzyme linking and regulation of specific phospholipase enzymes.

Amnion↗
PubMed1987

Preterm labor: stimulation of arachidonic acid metabolism in human amnion cells by bacterial products.

There is a strong association between preterm labor and infection. Some potentially pathogenic bacteria have phospholipase activity, and it has been suggested that release of phospholipase from these organisms may increase prostaglandin E2 synthesis in amnion cells and hence initiate preterm labor. In this study we established monolayer amnion cell cultures from tissue collected at elective cesarean section at term before labor. Cells were prelabeled with tritiated arachidonic acid and then further incubated after addition of 2%, 5%, or 10% (vol/vol) filtered medium in which either group B beta-hemolytic streptococcus, Streptococcus viridans, Escherichia coli, Bacteroides fragilis, or Lactobacillus had been growing. Tritiated arachidonic acid and its metabolites released by the amnion cells in these or control incubates were extracted from culture medium and separated by high-performance liquid chromatography. Addition of conditioned medium from each of the organisms with the exception of Lactobacillus caused an increase in overall arachidonic acid metabolism. There was an increase in the ratio of cyclooxygenase to lipoxgenase metabolism and in prostaglandin E2 production in particular when compared to controls. The profile of arachidonic acid metabolism in amnion cells following addition of filtered bacterial medium resembled that obtained from amnion cells cultured following spontaneous labor. We suggest that abnormal bacterial colonization of the genital tract may lead to an increase in arachidonic acid metabolism in amnion cells with an increase in prostaglandin E2 production and the consequent initiation of preterm labor.

Amnion↗
PubMed1987

The effects of lipoxygenase metabolites of arachidonic acid on human myometrial contractility.

The effects of the lipoxygenase products of arachidonic acid, 5- and 12-hydroxyeicosatetraenoic acid (5- and 12-HETE) and leukotriene B4 (LTB4), on the spontaneous contractility of lower uterine segment human myometrial strips obtained prior to labour have been studied in vitro. 5-HETE gave a dose- dependent (10-500ng) increase in both the rate of contractions and overall contractility of myometrial strips while 12-HETE and LTB4 had no effect at the same concentrations. Prostaglandin F2 alpha (50ng) contracted all myometrial strips in a similar pattern to 5-HETE but was approximately 10 times more potent. The effect of 5-HETE may be direct or perhaps indirect via interaction with the cyclo-oxygenase pathway. The findings do not disprove the contention that the onset of parturition may be characterised by a switch in arachidonic acid metabolism in intra-uterine tissues from lipoxygenase to cyclo-oxygenase products.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1987

Oestrogen receptor in the granulosa cell during postnatal development of the rat ovary.

Numbers of granulosa cells obtained from follicles of immature rats increased from 1.6 X 10(5) cells/ovary on day 8 to 7.1 X 10(6) cells/ovary on day 40 of age, the day of vaginal opening and first pro-oestrus. Very high levels of cytosol oestrogen receptor were found on day 8 (175,000 sites/cell) but by day 19 20,000 sites/cell were found. Nuclear receptor concentrations were highest on day 12 (5400 +/- 1470 (S.D.)sites/cell) and again on day 21 (5400 +/- 2300 sites/cell). After day 21 both cytosol and nuclear oestrogen receptor concentrations fell and remained low until nuclear concentrations rose at day 40. Two consecutive daily injections of FSH/LH (5 i.u.) increased cell number over control in animals killed on day 22, gave no significant alteration in animals killed on day 26 or 28 but decreased numbers in animals aged 32 and 35 days. Only on day 22 was the increase in cell number associated with an increase in nuclear oestrogen receptor concentrations. Indeed on days 32 and 35 increased nuclear receptor concentrations were associated with a decreased cell number.

Animals↗
PubMed1986

Characterisation of non-activated and activated estrogen- and antiestrogen-receptor complexes by high performance ion exchange chromatography.

The ionic species of cytosol estrogen receptors from mature rat uteri have been compared by HPIEC on a SynChrom AX-1000 column when complexed with either [125I]iodoestradiol, [3H]estradiol or [3H]4-hydroxy tamoxifen. Three species of receptors (isoforms) each suppressible by excess competitor were fractionated at identical salt concentrations regardless of ligand employed. One species eluted in the column void volume (10 mM) and the others at congruent to 90 mM and congruent to 155 mM phosphate. Activation of receptor complexes by increasing time of incubation with ligand from 1 to 24 h at 4 degrees C or addition of 10 mM GTP increased the proportion of the congruent to 90 mM species for all 3 ligands. The addition of 10 mM molybdate to homogenization and HPIEC buffers resulted in only two species being resolved at 10 and 110 mM phosphate. These species were again identical regardless of ligand employed. Increasing concentrations of estradiol (1-40 nM) tamoxifen (20 nM-4 microM) and 4-hydroxy tamoxifen (2-400 nM) were able to compete for binding of [125I]iodoestradiol to each of the three ionic species. Binding to each species was inhibited equally by each concentration of competitor. There was no preferential or unique association of estrogen or antiestrogen with any of the ionic species and all ligands gave identical ionic species of non-activated and activated receptor complexes.

Animals↗