Search PubMed⌕ Search

Biomedical subjects

S C Brooks

Publications and source records attributed to S C Brooks.

At least 37 records · Page 2Linked to original sources
PubMed1998

Caffeine abstinence augments the systolic blood pressure response to adenosine in humans.

Blood pressure and heart rate responses to adenosine infusion (35, 70, and 140 microg/kg/min, intravenously) were studied in 7 healthy men after 6, 30, 78, 150, and 318 hours of abstinence from regular caffeine use. The finding that caffeine abstinence augmented the systolic pressor response (from -1 +/- 2 mm Hg at 6 hours to +9 +/- 2 mm Hg at 318 hours; p = 0.01) but not the tachycardic response to adenosine has implications for current clinical and research applications of this purine.

Adenosine↗
PubMed1998

Angiotensin AT1 receptor blockade abolishes the reflex sympatho-excitatory response to adenosine.

We tested the hypothesis that endogenous angiotensin II participates in the direct and reflex effects of adenosine on the sympathetic nervous system. Nine healthy men were studied after 1 wk of the angiotensin II type I receptor antagonist losartan (100 mg daily) or placebo, according to a double-blind randomized crossover design. Bilateral forearm blood flows, NE appearance rates, and total body NE spillover were determined before and during graded brachial arterial infusion of adenosine (0.5, 1.5, 5, and 15 microg/100 ml forearm tissue) and nitroprusside. Adenosine increased total body NE spillover (P < 0.05) whereas nitroprusside did not. Losartan lowered BP (P < 0.05), had no effect on total body NE spillover at rest, or forearm vasodilation during either infusion, but reduced the systemic noradrenergic response to adenosine from 1.0+/-0.4 nmol/min on the placebo day to 0.2+/-0.3 nmol/min (P < 0.01), and forearm NE appearance rate in response to adenosine was lower in the infused, as compared with the contralateral arm (P = 0.04). The sympatho-excitatory reflex elicited by adenosine is mediated through pathways involving the angiotensin II type I receptor. Interactions between adenosine and angiotensin II may assume importance during ischemia or congestive heart failure and could contribute to the benefit of converting enzyme inhibition in these conditions.

Adenosine↗
PubMed1998

Polyoma middle T antigen in HL-60 cells accelerates hematopoietic myeloid and monocytic cell differentiation.

Expression of the polyoma virus middle T antigen in HL-60 cells accelerates their differentiation in response to both monocytic and granulocytic differentiation-inducing agents. Middle T-expressing cells treated with the granulocytic inducer retinoic acid or the monocytic inducer 1,25-dihydroxy vitamin D3 differentiated 24 h earlier than parental, mock-electroporated, or vector control cell lines. The rapid onset of differentiation correlated with an increase in the cellular level of the middle T protein as well as two known retinoic-acid-inducible markers in HL-60 cells: the paxillin and transglutaminase gene products. The accelerated functional differentiation response and expression of retinoic-acid-inducible markers indicate that middle T played a causal role in differentiation. Thus, expression of the polyoma middle T antigen in HL-60 cells enhanced a variety of molecular changes associated with cellular differentiation.

Antigens, Polyomavirus Transforming↗
PubMed1998

Changes in the structure of the ligand or substitutions to AF2 residues in the estrogen receptor make independent contributions to coactivator sensitivity by SRC-1.

The estrogen receptor (ER) is a ligand-inducible transcription factor which depends, in part, upon the C-terminal activation function (AF2) in order to regulate the expression of target genes. AF2 residues fold into an amphipathic alpha-helix on helix 12 of the ER, with hydrophobic and acidic faces. It is believed that AF2 mediates the gene regulatory activities of ligand-activated ER by interacting with coactivator proteins. We have analyzed the contribution of acidic AF2 residues to the process of ER coactivation by the steroid receptor coactivator, SRC-1. In HeLa cells, SRC-1 coexpression was found to restore transcriptional potency to otherwise inert complexes of wild type ER and 4-hydroxyestratrien-17beta-ol. SRC-1 coexpression also enhanced transcriptional activity of reporter genes induced by an ER mutant with neutral replacements to acidic AF2 residues, in response to E2 or 4-hydroxyestratrien-17beta-ol. By contrast, ER complexes from ICI164,384-treated HeLa cells were both transcriptionally inactive and coactivator insensitive. It is concluded that changes to the structure of the ligand or substitutions to acidic residues in the AF2 region of the receptor contribute independently to the control of coactivator sensitivity in ER.

Amino Acid Sequence↗
PubMed1998

Neural and hypotensive effects of angiotensin II receptor blockade.

Angiotensin II participates in the neural regulation of the heart and circulation at both central and peripheral sites. To explore the role of endogenous angiotensin II in blood pressure regulation, we conducted a randomized double-blind crossover trial in nine young healthy men (aged 33+/-3 [mean+/-SE] years) studied in the absence of salt restriction, comparing the effect of 1 week treatment with the angiotensin II receptor antagonist losartan (100 mg daily) against placebo with respect to the following variables, recorded during supine rest: intra-arterial blood pressure (BP), heart rate (HR), forearm vascular resistance and norepinephrine appearance rate, total body norepinephrine spillover, variability of BP and HR (spectral analysis), and baroreflex sensitivity for HR (gain of the transfer function from systolic BP to HR). Blood pressure was 119+/-7/66+/-4 mm Hg (systolic BP/diastolic BP) after 1 week of placebo and 112+/-6/61+/-3 mm Hg after 1 week of losartan (P<.05). Forearm vascular resistance tended to fall, from 42.3+/-6.9 U on placebo to 32.8+/-5.0 U with losartan treatment (P=.07). Losartan had no effect on HR (60+/-3 on placebo versus 59+/-2 beats per minute with losartan), total body norepinephrine spillover (3.0+/-0.8 versus 3.3+/-1.2 nmol/min), forearm norepinephrine appearance rate (3.8+/-1.1 versus 5.3+/-1.1 pmol/100 mL forearm tissue per minute), power in the high- or low-frequency components of the HR variability and BP variability spectra or on baroreflex sensitivity for HR. Endogenous angiotensin II contributes to the maintenance of supine BP in normal subjects, studied in the absence of sodium restriction. The fall in BP caused by losartan is accompanied by a resetting of the baroreflex regulation of HR and sympathetic outflow, but baroreflex sensitivity for heart rate is not altered. Therefore, the reduction in BP observed after short-term angiotensin type 1 receptor antagonism may be achieved through a direct effect on vascular tone rather than through a primary reduction in sympathetic outflow.

Adult↗
PubMed1997

Induction of the estrogen specific mitogenic response of MCF-7 cells by selected analogues of estradiol-17 beta: a 3D QSAR study.

Analogues of estradiol-17 beta (E2) have been evaluated for estrogen receptor (ER) binding affinity and mitogenic potential in the human breast cancer cell line MCF-7. These 42 compounds represent subtle modifications of the natural estrogen structure through the placement of hydroxyl, amino, nitro, or iodo groups around the ring system in addition to, or as replacement of, the 3- and 17 beta-hydroxyls of E2. The mitogenic activity of the analogues was found to be related to ER binding only to a limited extent. In order to elucidate structural features that are uniquely responsible for receptor binding affinity or mitogen potential of estrogens, the three-dimensional quantitative structure-activity (QSAR) method Comparative Molecular Field Analysis (CoMFA) was employed. Separate CoMFA models for receptor binding and cell growth stimulation were optimized through the use of various alignment rules and region step size. Whereas the CoMFA contour plots did outline the shared structural requirements for the two measured biological properties, specific topological features in this set of estrogens were delineated that distinguish mitogenic potential from ER binding ability. In particular, steric interference zones which affected growth extend in a band from above the A-ring to position 4 and below, whereas the ER binding steric interference zones are limited to isolated polyhedra in the 1, 2 and 4 positions and the alpha face of the B-ring. In addition, electronegative features located around the A-, B-, or C-rings contribute to receptor affinity. However, growth is dependent only on electronegative and electropositive properties near the 3-position. In a final QSAR model for the mitogenic response, the value of ER binding was included along with structural features as a descriptor in CoMFA. The resulting 3D-QSAR has the most predictive potential of the models in this study and can be considered a prototype model for the general evaluation of a steroidal estrogen's growth stimulating ability in MCF-7 cells. For example, the location of D-ring contours illustrate the model's preference for 17 beta-hydroxy steroids over the less mitogenic 17 alpha- and 16 alpha-hydroxy compounds. In addition, the enhanced mitogenic effect of steric bulk in the 11 alpha-position is also evident. The QSAR studies in this report illustrate the fact that while ER binding may be a required factor of the estrogen dependent growth response in MCF-7 cells, particular structural characteristics, in addition to those responsible for tight receptor binding, must be present to induce an optimal mitogenic response. Therefore, this report demonstrates that the CoMFA QSAR method can be utilized to characterize structural features of test compounds that account for different types of estrogenic responses.

Breast Neoplasms↗
PubMed1997

An RXR-selective analog attenuates the RAR alpha-selective analog-induced differentiation and non-G1-restricted growth arrest of NB4 cells.

NB4, a human acute promyelocytic leukemia cell line expressing the promyelocyte-retinoic acid receptor alpha (PML-RAR alpha) hybrid protein was treated with RAR- and retinoid X receptor (RXR)-selective analogs to determine their effects on cell proliferation, retinoblastoma (RB) tumor-suppressor protein phosphorylation, and differentiation. An RAR- or just RAR alpha-selective analog alone induced similar cell population growth arrest, cell cycle arrest without restriction to G1, hypophosphorylation of RB, and myelomonocytic cell surface differentiation marker expression (CD11b). In addition, an RAR alpha antagonist could inhibit the effects of the RAR alpha agonist completely. The RAR alpha-selective analog-elicited response was attenuated by simultaneous addition of various RXR-selective analogs. In contrast, each of the RXR-selective analogs was unable to induce any of the cellular responses analyzed. The growth arrest of NB4 cells is not G1-restricted and occurs at all points in the cell cycle. Cells growth arrested by treatment with an RAR alpha-selective analog show primarily hypophosphorylated RB. When these cells are sorted into G1 or S + G2/M subpopulations by flow cytometry, hypophosphorylated RB protein was in G1 as well as S + G2/M cells. This suggests that the hypophosphorylated RB protein may be mediating the growth arrest of NB4 cells at all points in the cell cycle. These results are consistent with an involvement of PML-RAR alpha and/or RAR alpha in the transduction of the retinoid signal in NB4 cells.

Cell Cycle↗
PubMed1997

Neutral mutations to three acidic AF2 residues in the mouse estrogen receptor confer agonist activity to A-ring isomers of estradiol.

The ability of the estrogen receptor (ER) to function as a ligand-mediated transcription factor involves the activation function-2 (AF2) in the hormone binding domain (HBD). Although several types of ligand bind to the ER, AF2 functions selectively, as it is activated by estradiol (E2) but not by antiestrogens. The mechanism used by AF2 to interpret the chemical and structural information encoded in the bound ligand, and to transfer this information to other transcriptional regulatory proteins on the promoters of estrogen-regulated genes, is unknown at present. To address this issue, we have examined the activities of two mouse ERs with mutations in the AF2 region. One incorporated changes in three acidic residues (pJ3MOR, D542N/E546Q/D549N) on the polar face of the putative AF2 alpha-helix, whereas the other contained alterations in two hydrophobic amino acids (pJ3MOR, L543D/L544A) on the non-polar face. Transcriptional activity was measured with chloramphenicol acetyltransferase (CAT) reporter genes including a minimal (JA12) or a complex (pS2tkCAT) promoter. In transient cotransfection assays using COS-1 cells, it was found that A-ring isomers of E2, which are inactive or behave as antagonists with the wild-type ER, acted as agonists when the neutral AF2 mutant ER and the pS2tkCAT promoter were tested. On the other hand, when the mutant ER with changes in key hydrophobic residues was used with this same promoter, the estrogen antagonist, ICI 164,384, acted as an agonist. The findings in this report establish a role for acidic AF2 amino acids, and confirm the contributions made by hydrophobic residues, in the interpretation of ligand identity and in the transmission of this information to the transcriptional regulatory apparatus. Critical residues on both sides of the AF2 alpha-helix are, therefore, likely to be involved in distinguishing between ligands with either extensive or subtle alterations in structure, and in mediating this information to the regulatory proteins on estrogen-responsive genes.

Animals↗
PubMed1996

Myeloid differentiation and retinoblastoma phosphorylation changes in HL-60 cells induced by retinoic acid receptor- and retinoid X receptor-selective retinoic acid analogs.

The ability of subtypes of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) singly and in combination to elicit myeloid differentiation, G1/0-specific growth arrest, and retinoblastoma (RB) tumor suppressor protein dephosphorylation was determined in the human myeloblastic leukemia cell line HL-60 using subtype-selective retinoic acid (RA) analogs. RA analogs that selectively bind only to RARs (Am580 and/or TTNPB) or to RXRs (Ro 25-6603, SR11237, and/or SR11234) did not elicit the above-mentioned three cellular responses. In contrast, simultaneous treatment with both an RAR-selective ligand (Am580 or TTNPB) and an RXR-selective ligand (Ro 25-6603, SR11237, or SR11234) induced all three cellular processes. An RAR alpha-selective ligand used with an RXR-selective ligand generated the same responses as did all-trans RA or 9-cis RA, which affect both families of receptors, suggesting an important role for RAR alpha among RAR subtypes in eliciting cellular response. Consistent with this finding, the RAR alpha antagonist, Ro 41-5253, reduced the level of the cellular responses elicited by treatment with an RAR alpha-selective ligand plus RXR-selective ligand. The coupling of the shift of RB to its hypophosphorylated form with G1/0 arrest and differentiation in response to ligands is consistent with a possible role of RB as a downstream target or effector of RAR alpha and RXR in combination.

Benzoates↗
PubMed1996

Characterization of the estrogen receptor transfected MCF10A breast cell line 139B6.

There has been increasing evidence which suggests that abnormal expression of the estrogen receptor (ER) protein in nonmalignant breast tissue may be important in the carcinogenic process. To examine the effects of ER expression in immortalized nonmalignant mammary epithelial cells, an expression vector containing human ER cDNA was transfected into the ER negative human breast cells, MCF10A. Characterization of a clone stably expressing ER, 139B6, provided evidence for the regulated synthesis of a functional ER capable of binding estradiol-17 beta (E2) and undergoing processing. Expression of the ER gene did not enable E2 to stimulate endogenous genes [progesterone receptor (PgR), pS2, cathepsin D and TGF alpha] which normally respond to estrogens in breast cancer cells. The ER in 139B6 cells was, however, capable of inducing expression of an ERE-regulated reporter gene, indicating its ability to interact with transcriptional machinery. Furthermore, cultures in log growth displayed a slight increase in doubling time in the presence of E2. These results indicate that ER expression alone is not sufficient to induce a transformed phenotype. Thus, the 139B6 cell line should provide a new model for determining what additional changes lead to increased growth potential in response to E2 and for exploring how E2 itself may help bring about changes leading to progression of preneoplastic breast epithelial cells.

Actins↗
PubMed1996

Crystal structure, receptor binding, and gene regulation of 2- and 4-nitroestradiols.

Crystal structures of 2-nitroestradiol and 4-nitroestradiol showed two different molecular conformations for each compound. The crystal structure of 4-nitroestradiol, as well as that of 4-nitroestrone-3-methyl ether, displayed a nitro group in which the oxygens were perpendicular to the aromatic ring and were this nonconjugating. On the other hand, the nitro-oxygens in 2-nitroestradiol were periplanar, with the aromatic ring permitting conjugating. This latter structure bound to estrogen receptor with 1/1000th the affinity of estradiol and was inefficient in gene stimulation. 4-Nitroestradiol possessed a relative binding affinity 40-fold greater than that of the 2-nitro derivative and actively induced responsive genes at a concentration of 10(-8) M. Whereas binding affinity can be explained primarily by polar groups and skeletal structure, gene induction may be linked to electronic induction in ring A that causes a requisite electronegative isopotential around the molecule. This electronegative characteristic also produces conformational changes in the alicyclic backbone of the estrogen, specially ring B, which could interfere with the molecular fit of the nitroestradiols with estrogen receptor.

Cell Line↗
PubMed1995

A molecular modeling analysis of diethylstilbestrol conformations and their similarity to estradiol-17 beta.

Crystallographic and computer modeling studies throughout the last 25 years have shown the structure of diethylstilbestrol (DES) to exist in two symmetrical or one asymmetrical conformation. As a result of specific comparisons to estradiol-17 beta (E2), the asymmetrical DES conformer has been suggested as the geometry possessing estrogenic activity. In the present study, a more complete set of DES conformations has been elucidated through the use of computer modeling. All previously defined DES geometries were found within this new set of ten structural forms. Differences between the molecular mechanics heat of formation energies of the ten conformers, as well as the transition energies separating them from each other, were found to be less than 1 kcal/mol. Additionally, a computer-based molecular alignment method was employed to quantitatively compare the steric and electrostatic molecular features of each DES conformer relative to E2. All ten DES structures were found to have shape relationships similar to E2. Thus, a model for the estrogen action of DES is presented whereby this stilbene can favorably interact with the estrogen receptor regardless of the conformation or orientation of the initial ligand-receptor association.

Chemical Phenomena↗
PubMed1995

Induction of tissue plasminogen activator mRNA and activity by structurally altered estrogens.

The effect of structure of the estrogen ligand on the accumulation of tPA mRNA and the activity of extracellular fibrinolytic enzyme has been examined in cultures of MCF-7 cells. Estradiol(E2)-stimulated fibrinolytic activity was preceded by an increase in actinomycin D sensitive tPA mRNA synthesis which peaked at 18 h. Ten A- and D-ring structural analogs of E2 affected tPA mRNA accumulation and extracellular fibrinolytic activity. Only in the case of two A-ring isomers (2- and 4-hydroxyestratrien-17 beta-ol) was the decreased effect of the ligand's structural change on tPA mRNA accumulation and fibrinolysis not explained by a comparable decline in affinity of the ligand for estrogen receptor. Both of these analogs functioned as antiestrogens. The stimulatory capacity of androstanediols on the tPA gene required that the 3-hydroxyl group be positioned in the beta-configuration. Absence of the 17 beta-hydroxy group was beneficial to the maximum accumulation of tPA mRNA. As has been reported for other estrogen responsive genes (progesterone receptor, cathepsin D and pS2), regulation by estrogens is not related directly to the affinity of the ligand for ER, but this activity may be determined by the location of the electronegative isopotential above the A-ring of estrogenic ligands.

Dactinomycin↗
PubMed1995

Relationship between estrogen structure and conformational changes in estrogen receptor/DNA complexes.

The effect of estrogen structure on the conformation of the complex formed with estrogen receptor (ER) and the consensus estrogen response element (EREc) has been examined with gel mobility shift assay. Proteins in MCF-7 cell extracts formed three distinct complexes with ERE. Only the slowest moving complex contained ER as indicated by binding with anti-ER antibodies H222 and D547. This ER-ERE complex displayed increased electrophoretic mobility when formed in the presence of estradiol (E2) and bound radiolabeled 16 alpha-iodoestradiol. The antiestrogen ICI 164,384 decreased the mobility of the ER-ERE complex and blocked the effect of E2. The results reported here indicate that the position and location of hydroxyl groups on the estratriene nucleus is an important factor in determining the mobility of ER-EREc (or a variant ERE) in gel shift assays. The ability of E2 analogs to cause conformational changes detectable as altered mobility was not directly related either to their binding affinity for ER or to their ability to activate E2 responsive genes. Although several dihydroxyestrogens (estradiol-16 alpha, 1- and 2-hydroxyestratrien-17 beta-ol) caused an increase in the mobility of the ER-EREc, other ligands (estradiol-17 alpha, 4-hydroxyestratriene-17 beta-ol, 3-hydroxy estratriene, estratrien-17 beta-ol and 5-androsten-3 beta, 17 beta-diol) with a capacity for activating at least some E2 responsive genes in MCF-7 cells had little or no effect. On the basis of these and previously published results, it can be concluded that specific structure features of estrogens are responsible for conformational changes of ER-ERE complexes detectable in gel-shift assays. Furthermore, the identified structural characteristics of the ligand which are required for gel-shift are not the same as those previously reported to be essential for stimulation of transcriptional activity of ER.

Base Sequence↗
PubMed1994

Effect of A-ring isomers of estradiol-17 beta on gene products in MCF-7 cells.

Two-dimensional polyacrylamide gel-electrophoresis analysis of in vitro translation products from extracted cellular mRNAs was utilized to examine the effect of A-ring isomers of estradiol (E2) on the synthesis of proteins involved in the response of MCF-7 cells to estrogens. An 8 h pulse with 10(-8) M E2 showed 11 polypeptides of interest, 9 displayed a transient increase in mRNA accumulation and 2 showed a temporary decreased level in the presence of this hormone. A distinct set of 2 mRNAs displayed increased amounts only after a 24 h E2 pulse. Position of the A-ring hydroxyl group on the estratrien-17 beta-ol moiety had a discriminatory effect on the mRNAs for the 11 polypeptides responsive to E2. The accumulation of three mRNAs (A, C, and E) were increased by the 3 A-ring isomers (1-, 2-, and 4-hydroxyestratrien-17 beta-ol) to a degree comparable to that brought about by E2. One mRNA (H) was decreased by all estrogens. The pattern of responses depicted in the remaining 7 polypeptides was different depending on the position of the A-ring hydroxyl group of the estrogen. Subtle changes in the structure of E2 appear to attenuate the ability of this natural ligand to regulate certain estrogen responsive genes and not others. This phenomenon may be related to the interaction of TAF-2 in ligand bound receptor with the various regulators in the promoter region of specific estrogen responsive genes.

Breast Neoplasms↗
PubMed1994

Molecular modeling of steroidal estrogens: novel conformations and their role in biological activity.

Since the structure and conformation of many estrogenic ligands cannot be described with X-ray crystallographic studies, molecular modeling techniques must be used to generate their 3-dimensional structures. The potential of three molecular modeling methods to simulate the X-ray crystallographic geometry of estradiol-17 beta and various analogs (estratrien-1,17 beta-diol, estratrien-2,17 beta-diol, estratrien-3,11 alpha,17 beta-triol, estratrien-3,11 beta,17 beta-triol, 9 beta-estratrien-3,17 beta-diol-11-one) have been compared. MMP2 molecular mechanics as well as the MOPAC semi-empirical molecular orbital methods, AM1 and PM3, were examined in these studies of estrogens with unique ring distortions. Whereas all three methods were able to simulate reasonable estrogen structures, the MMP2 method was found to reproduce the X-ray geometry of estrogens better than the MOPAC methods. The contribution of crystal packing distortions on the X-ray structures in these comparisons is discussed. Additionally, a molecular modeling dynamics method for the systematic conformational searching of steroidal estrogens is presented. For each estrogen examined, conformational searching produced at least one unique steroid conformation in addition to the X-ray crystallographic geometry. The MMP2 potential energy of predicted conformations and transition barriers of these estrogens has been shown to be less than the free energy of receptor binding. Thus, it is conceivable that estrogen ligands which can exist in a number of conformations may be converted to a preferred geometry by binding within the specific site of receptor. Furthermore, it is suggested that conformational flexibility of estrogens may be an important property of specific ligands for the estrogen receptor.

Crystallography, X-Ray↗
PubMed1994

Skeletal conformations and receptor binding of some 9,11-modified estradiols.

The effect of the modification of the 9-11 positions on the skeletal conformation of estradiol (E2) has been analyzed by X-ray crystallography and MM2 molecular mechanics. The 11 beta-hydroxyl and 11-keto analogs of E2 maintained ring conformations which were similar to the natural hormone (E2). Introduction of a double bond at position 9-11 induced a flattening of the entire steroid molecule. An 11 alpha-hydroxyl group brought about significant changes in the alicyclic rings of E2. 9 beta-Estradiol and 11-keto-9 beta-estradiol formed ring conformations which were significantly bent from E2 (below the plane of the A-ring). Examination of the affinity of these C-ring analogs of E2 for the human estrogen receptor has shown extreme variations. A hydroxyl group placed either alpha or beta at the 11-position yielded ligands with vastly different and reduced affinities for the receptor. The low affinity of 11 alpha-hydroxyestradiol (1/300th of E2) may be due to the drastic structural change induced in the alicyclic portion of the molecule, as well as, to the steric or electrostatic effects of the alpha-hydroxyl group upon the receptor protein. An 11 beta-hydroxyl group diminished the receptor binding to 1/60th that of E2 without alicyclic ring distortions, whereas a 9-11 unsaturation reduced the binding to 1/5th although this steroid displayed a flattening of rings B, C, and D. The 11-keto function, which had little effect on the conformation of the estrogen nucleus, reduced the affinity of this ligand to 1/1000th that of E2. The negative bend at the C-ring of 11-keto-9 beta-estradiol and 9 beta-estradiol prevented these ligands from binding receptor. Some of the observed receptor interactions were related to structural alterations in the estrogen ring system induced by modifications on the 9-11 region.

Crystallography, X-Ray↗