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J A Holt

Publications and source records attributed to J A Holt.

At least 19 recordsLinked to original sources
PubMed1999

The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis.

betaarrestins mediate the desensitization of the beta2-adrenergic receptor (beta2AR) and many other G protein-coupled receptors (GPCRs). Additionally, betaarrestins initiate the endocytosis of these receptors via clathrin coated-pits and interact directly with clathrin. Consequently, it has been proposed that betaarrestins serve as clathrin adaptors for the GPCR family by linking these receptors to clathrin lattices. AP-2, the heterotetrameric clathrin adaptor protein, has been demonstrated to mediate the internalization of many types of plasma membrane proteins other than GPCRs. AP-2 interacts with the clathrin heavy chain and cytoplasmic domains of receptors such as those for epidermal growth factor and transferrin. In the present study we demonstrate the formation of an agonist-induced multimeric complex containing a GPCR, betaarrestin 2, and the beta2-adaptin subunit of AP-2. beta2-Adaptin binds betaarrestin 2 in a yeast two-hybrid assay and coimmunoprecipitates with betaarrestins and beta2AR in an agonist-dependent manner in HEK-293 cells. Moreover, beta2-adaptin translocates from the cytosol to the plasma membrane in response to the beta2AR agonist isoproterenol and colocalizes with beta2AR in clathrin-coated pits. Finally, expression of betaarrestin 2 minigene constructs containing the beta2-adaptin interacting region inhibits beta2AR endocytosis. These findings point to a role for AP-2 in GPCR endocytosis, and they suggest that AP-2 functions as a clathrin adaptor for the endocytosis of diverse classes of membrane receptors.

Adaptor Protein Complex alpha Subunits↗
PubMed1998

Transmembrane protein insertion orientation in yeast depends on the charge difference across transmembrane segments, their total hydrophobicity, and its distribution.

The determinants of transmembrane protein insertion orientation at the endoplasmic reticulum have been investigated in Saccharomyces cerevisiae using variants of a Type III (naturally exofacial N terminus (Nexo)) transmembrane fusion protein derived from the N terminus of Ste2p, the alpha-factor receptor. Small positive and negative charges adjacent to the transmembrane segment had equal and opposite effects on orientation, and this effect was independent of N- or C-terminal location, consistent with a purely electrostatic interaction with response mechanisms. A 3:1 bias toward Nexo insertion, observed in the absence of a charge difference, was shown to reflect the Nexo bias conferred by longer transmembrane segments. Orientation correlated best with total hydrophobicity rather than length, but it was also strongly affected by the distribution of hydrophobicity within the transmembrane segment. The most hydrophobic terminus was preferentially translocated. Insertion orientation thus depends on integration of responses to at least three parameters: charge difference across a transmembrane segment, its total hydrophobicity, and its hydrophobicity gradient. Relative signal strengths were estimated, and consequences for topology prediction are discussed. Responses to transmembrane sequence may depend on protein-translocon interactions, but responses to charge difference may be mediated by the electrostatic field provided by anionic phospholipids.

Amino Acid Sequence↗
PubMed1997

Regulation of expression of the steroidogenic acute regulatory protein (StAR) gene: a central role for steroidogenic factor 1.

Steroidogenic acute regulatory protein (StAR) plays a critical role in regulating the rate-limiting step in steroid hormone synthesis, cholesterol side-chain cleavage. StAR gene expression is transcriptionally controlled in the gonads by gonadotropic hormones via a cAMP second message. We have begun to analyze factors responsible for the transcriptional activation of the StAR gene. The human StAR gene promoter has at least two cis elements that govern basal and cAMP-regulated gene expression. One of these elements (the distal element) is a consensus binding sequence for the orphan nuclear receptor transcription factor, steroidogenic factor 1 (SF-1); the other (the proximal element) is a related motif. The human StAR promoter is not active in BeWo choriocarcinoma cells, but is functional and cAMP-responsive in murine Y1 adrenal cortical tumor cells. Cotransfection of a plasmid expressing SF-1 allows a StAR promoter construct to function in BeWo cells. Other orphan nuclear transcription factors do not support StAR promoter function in BeWo cell hosts. Deletion or mutation of the distal and proximal cis elements individually substantially reduces SF-1-supported StAR promoter activity. The distal site binds SF-1 with high affinity, whereas the proximal site binds SF-1 with lower affinities. These findings demonstrate a requirement for SF-1 for human StAR gene expression.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Estrogen-mediated mitochondrial cholesterol transport and metabolism to pregnenolone in the rabbit luteinized ovary.

We investigated the mechanisms of luteotropic actions of estradiol on steroidogenesis. To this end, we examined, in vitro, the metabolism of cholesterol from endogenous or exogenous sources for pregnenolone production in rabbit luteinized ovarian cell mitochondria isolated from pseudopregnant animals in various states of stimulation by estradiol. We found that estradiol-mediated regulation of mitochondrial cholesterol metabolism for pregnenolone production differs from the mechanisms of regulation reported for steroidogenic protein/polypeptide hormones in the following respects: 1) in the estradiol-sensitive, luteinized-ovary, rabbit model, temporary blockage of cytochrome P-450 cholesterol side-chain cleavage enzyme by aminoglutethimide treatment in vivo has no effect on mitochondrial pregnenolone production in vitro after the aminoglutethimide is removed, indicating no additional capacity for upstream cholesterol storage; 2) preincubating mitochondria at 37 degrees C fails to increase subsequent pregnenolone synthesis in response to the addition of isocitrate; and 3) exogenously added cholesterol does not readily enter the steroidogenic pool of cholesterol unless the endogenous cholesterol pool is first depleted. These new observations indicate that estradiol increases the usable steroidogenic cholesterol pool in rabbit ovarian mitochondria. Also, 1) they are consistent with a putative requirement for the participation of one or more estrogen-sensitive protein factors to enhance cholesterol trafficking to the inner mitochondrial membrane, and 2) they complement the observation of estrogen-dependent expression of steroidogenic acute regulatory protein in rabbit luteal tissue.

Aminoglutethimide↗
PubMed1996

Steroidogenic acute regulatory protein (StAR) retains activity in the absence of its mitochondrial import sequence: implications for the mechanism of StAR action.

Steroidogenic acute regulatory protein (StAR) plays a critical role in steroid hormone biosynthesis, presumably by facilitating the delivery of cholesterol to P450scc in the inner mitochondrial membranes. StAR is synthesized as a 37-kDa preprotein that is processed to a 30-kDa mature form by cleavage of an N-terminal mitochondrial import sequence. To identify structural features required for StAR biological activity, we mutated the human StAR cDNA, including the deletion of N- and C-terminal sequences, and examined the ability of the mutants to promote steroidogenesis and enter the mitochondria of transfected COS-1 cells. Deletion of up to 62 residues from the N terminus (N-62) did not significantly affect steroidogenesis-enhancing activity. The N-terminal deletion mutants were associated with mitochondria-enriched fractions, but import and processing were progressively impaired with increasing length of the deletion. Immunogold electron microscopy and in vitro import assays showed that the active N-62 mutant was not imported into the mitochondria. Removal of the 28 C-terminal amino acids (C-28) inactivated StAR. Deletion of the C-terminal 10 amino acids (C-10) reduced steroidogenic activity by 53%, while truncation of the last 4 amino acids had no effect. The C-28 mutant StAR was not efficiently imported into mitochondria or processed, whereas some of the C-10 mutant was processed, indicating that import had occurred. We conclude that in the COS-1 cell system used, StAR does not need to enter into mitochondria to stimulate steroidogenesis and that residues in the C terminus are essential for steroidogenesis-enhancing activity. These findings imply that StAR acts via C-terminal domains on the outside of the mitochondria.

Animals↗
PubMed1996

Steroidogenic factor 1-dependent promoter activity of the human steroidogenic acute regulatory protein (StAR) gene.

Steroidogenic acute regulatory protein (StAR) is required for efficient adrenal cortical and gonadal but not trophoblast steroid hormone synthesis. StAR gene expression in gonadal cells is stimulated by tropic hormones acting through the intermediacy of cAMP. DNA sequence analysis of the human StAR gene promoter revealed two motifs resembling binding sites for steroidogenic factor 1 (SF-1), a member of the orphan nuclear receptor transcription factor family that controls expression of steroidogenic hydroxylases. The 5'-most sequence (distal site) is a consensus SF-1 binding site. The proximal site is a consensus estrogen receptor binding half-site. The StAR gene promoter is not active in BeWo choriocarcinoma cells, COS-1 cells, HeLa cells, or SK-OV-3 ovarian adenocarcinoma cells, all of which do not express significant levels of SF-1 mRNA. Introduction of SF-1 into these cells stimulated StAR promoter activity, particularly in response to cAMP. Two orphan nuclear transcription factors that bind to sequences similar to SF-1 sites, NGFI-B/Nur77 and RNR-1, did not support cAMP-stimulated StAR promoter activity in BeWo cells. Mutation of the distal putative SF-1 binding site reduced basal and cAMP-stimulated promoter activity in BeWo cells by 82% and 71%, respectively. Mutation of the proximal putative SF-1 binding site reduced basal and cAMP-stimulated promoter activity by 89% and 96%, respectively. Mutations in both sites reduced basal promoter activity to 7% of wild type promoter activity and cAMP-stimulated promoter activity to less than 5% of the wild type. Deletion analyses of promoter activity were consistent with the mutation studies. Electrophoretic mobility shift assays (EMSAs) demonstrated that the distal site binds to SF-1 expressed in COS-1 cells and to an SF-1-GST fusion protein with high affinity, but that the mutated distal sequence does not. An anti-SF-1 antibody ablated the characteristic SF-1-DNA complex with the distal sequence. The proximal site formed a number of protein-DNA complexes with COS-1 cell extracts, but appeared to have at best only very modest affinity for SF-1. Collectively, our findings demonstrate that SF-1 plays a key role in controlling the basal and cAMP-stimulated expression of the StAR gene. SF-1 can function at two distinct sites in the human StAR gene promoter, apparently by two different types of interaction, to control transcription.

Base Sequence↗
PubMed1996

Accelerated fetal lung maturity profiles and maternal cocaine exposure.

OBJECTIVE: To determine the effect of maternal cocaine exposure on fetal lung maturity as measured by surfactant-albumin ratios determined by the TDx-FLM test. METHODS: A case-control study design was used to compare fetal lung maturity as assessed by a surfactant-albumin ratio assay (TDx-FLM) in amniotic fluid (AF) obtained from women who were known to use cocaine and those who were not known to use cocaine during the study pregnancy. Multiple logistic regression procedures were used to control for gestational age and possible confounders, such as obstetric and nonobstetric complications, other substance abuse, race, infant sex, and payer status. RESULTS: Maternal cocaine use during pregnancy was associated with an accelerated fetal lung maturity profile (adjusted odds ratio [OR] 2.04, 95% confidence interval [CI] 1.04-4.00) as determined by the TDx-FLM test. Other variables found to be statistically significant predictors of a mature fetal lung profile were cigarette smoking during the current pregnancy (OR 1.61, 95% CI 1.02-2.56). Preterm labor, preterm rupture of membranes, nonobstetric illness during pregnancy, and exposure to other abused substances were not associated with accelerated fetal lung maturity. CONCLUSION: Maternal cocaine use during pregnancy is associated with a doubling of the probability of a mature fetal lung profile as determined by TDx-FLM analysis of AF. Tobacco use is also a predictor of accelerated fetal lung maturity profiles.

Adolescent↗
PubMed1995

Structure of the human steroidogenic acute regulatory protein (StAR) gene: StAR stimulates mitochondrial cholesterol 27-hydroxylase activity.

Steroidogenic acute regulatory protein (StAR) plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. We determined the organization of the StAR structural gene, mapped to 8p11.2. The gene spans 8 kb and consists of seven exons interrupted by six introns. The 1.3 kb of DNA upstream from the transcription start site directed expression of a luciferase reporter gene in mouse Y-1 adrenal cortical tumor cells but not in BeWo choriocarcinoma cells. Reporter gene expression in the Y-1 cells was increased more than 2-fold by 8-Br-cAMP, indicating that the 1.3 kb DNA fragment contains sequences that confer tissue-specific expression and cAMP regulation. The sequence of a related StAR pseudogene, mapped to chromosome 13, lacks introns and has an insertion, numerous substitutions, and deletions. Expression of StAR in COS-1 cells cotransfected with cholesterol 27-hydroxylase (P450c27) and adrenodoxin resulted in a 6-fold increase in formation of 3 beta-hydroxy-5-cholestenoic acid, demonstrating that StAR's actions are not specific to steroidogenesis but extend to other mitochondrial cholesterol-metabolizing enzymes.

Animals↗
PubMed1995

Human sterol carrier protein x/sterol carrier protein 2 gene has two promoters.

The human sterol carrier protein x (SCPx)/sterol carrier protein 2 (SCP2) gene gives rise to two mRNAs: a 2.8 kb mRNA encoding SCPx, a peroxisome-associated thiolase, and a 1.5 kb mRNA encoding SCP2, which is thought to be an intracellular lipid transfer protein. The SCPx/SCP2 gene is highly expressed in organs involved in lipid metabolism, but the relative abundance of SCPx and SCP2 mRNAs varies. Here we report that the two transcripts are produced under the direction of two independent promoters. We determined the DNA sequence of 3.4 kb of the proximal promoter governing the transcription of SCPx sequences. The promoter governing the transcription of SCP2 sequences was identified 45 kb downstream from the SCPx promoter in intron XI. This promoter initiates transcription within exon XII. Both the SCPx and SCP2 promoters lack TATA boxes and initiate transcription at multiple sites. They share features that are found in the promoters of genes encoding other peroxisomal proteins. The basal activities of the two promoters were tested as fusion gene constructs in selected host cells, including BeWo choriocarcinoma cells, HepG2 hepatoblastoma cells, murine Y1 adrenocortical tumor cells, and Balb 3T3 fibroblasts. Cell host-specific patterns of promoter activity were observed. In addition, 8-Br-cAMP and phorbol myristate acetate were found to increase SCPx promoter activity in a host cell-specific manner. The SCP2 promoter was not significantly influenced by these agents.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1995

Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13.

Steroidogenic acute regulatory protein (StAR) appears to mediate the rapid increase in pregnenolone synthesis stimulated by tropic hormones. cDNAs encoding StAR were isolated from a human adrenal cortex library. Human StAR, coexpressed in COS-1 cells with cytochrome P450scc and adrenodoxin, increased pregnenolone synthesis > 4-fold. A major StAR transcript of 1.6 kb and less abundant transcripts of 4.4 and 7.5 kb were detected in ovary and testis. Kidney had a lower amount of the 1.6-kb message. StAR mRNA was not detected in other tissues including placenta. Treatment of granulosa cells with 8-bromo-adenosine 3',5'-cyclic monophosphate for 24 hr increased StAR mRNA 3-fold or more. The structural gene encoding StAR was mapped using somatic cell hybrid mapping panels to chromosome 8p. Fluorescence in situ hybridization placed the StAR locus in the region 8p11.2. A StAR pseudogene was mapped to chromosome 13. We conclude that StAR expression is restricted to tissues that carry out mitochondrial sterol oxidations subject to acute regulation by cAMP and that StAR mRNA levels are regulated by cAMP.

Animals↗
PubMed1995

Comparisons of radioiodoestradiol blood-tissue exchange after intravenous or intraarterial injection.

PURPOSE: Our study determines and compares how the major organs of large animals handle exogenous halogenated bioactive sex steroids within the first minutes after their i.v. or i.a. injection. The rationale is that an understanding is needed of the acute physiological events because they affect decisions for how to optimize delivery of radiohalogenated sex steroid receptor ligands for purposes of medical imaging and modes of radiotherapy. METHODS AND MATERIALS: We used an indicator dilution technique that allows monitoring of blood-tissue exchange of radioactivity in a continuous manner in anesthetized surgically prepared swine. RESULTS: In swine, with by-passed liver circulation, the lungs allow the vast majority of [I-125]-16 alpha-iodo-17 beta-estradiol ([I-125]E) to be extracted from the blood perfusing the lung in the initial transit after i.v. injection in vivo. Similar outcome was observed for most major organs, including the CNS, intestines, spleen, peripheral appendages, and kidneys after i.a. injection of [I-125]E in vivo. However, within minutes the organs released the [I-125]E in its original chemical form back into the vascular system, with the exception of estrogen receptor (ER) rich tissues and the kidneys that retained the [I-125]E in its original form, although in the kidneys a nonpolar metabolite also accumulated. CONCLUSION: Our experiments confirm in a large animal model that radioiodoestradiol can be sequestered or concentrated in ER-rich sites. The liver and sex steroid receptor-rich organs modify considerably, by metabolism and sequestration, respectively, the acute distribution of bioactive steroids. Our data indicate potential for detection of ER in vivo in hormone-sensitive tumors, that is, in breast and endometrial cancers, and offer improved understanding of the recent studies in subjects with breast cancer that demonstrated that receptor imaging in vivo of steroid receptors with high-affinity radiolabeled ligands is possible in a clinical setting.

Animals↗
PubMed1995

Some characteristics of the glutathione cycle revealed by ionising and non-ionising electromagnetic radiation.

The cyclic reaction of GSH-->GSSG-->GSH (designated R(exp) or R(e)) obeys the three specific features of life by producing energy in exponential quantities relative to time, is in effect irreversible and is inherited from generation to generation. In multicellular life, this reaction produces the energy for mitosis and is kept in controlled inactivity until needed to maintain perfection of form and function by energising mitosis. The immediate control of Re appears to be feedback process-dependent on the concentration of GSSG. Ultra high-frequency electromagnetic radiation of 434 MHz (UHF) will change Re from inactive to active and, in so doing, it causes resonance and/or fluorescence of the glutathione cycle which changes its radiosensitivity. Re is the primary direct target of ionising radiation and produces the energy for mitosis. Clinical observations suggest that, in the normal cell, Re is inactive and is not killed by 3 x 2700 rads or 6 x 1650 rads yet, when active, its sensitivity value (DO) is approximately 160 rads. Using the standard radiobiological equation of response to ionising radiation, it can be deduced that radiosensitive cancers have two or three Re units active per cell and radioresistance increases in proportion to the number of potentially active Re units per cell. Re appears to be the main cause of cancers' increased conductivity of electricity compared with normal tissue. In cancer therapy, UHF is the best radiosensitiser ever discovered (up to two or more decades). Re is also intelligent compared with non-exponential reactions but cannot be the basis of intellectual brain functions which must be based on non-electrical chemical processes.

Adolescent↗
PubMed1995

T-->A transversion 11 bp from a splice acceptor site in the human gene for steroidogenic acute regulatory protein causes congenital lipoid adrenal hyperplasia.

Congenial lipoid adrenal hyperplasia (lipoid CAH) is the most severe form of CAH. Affected individuals can make no adrenal or gonadal steroids. All affected individuals are phenotypic females irrespective of gonadal sex, and frequently die in infancy if mineralocorticoid and glucocorticoid replacements are not instituted. Recent data implicate the steroidogenic acute regulatory (StAR) protein in this disorder. We now describe a 46,XY patient of Vietnamese ancestry with lipoid CAH who had a somewhat milder form of the disease. Diagnosis was at 10 weeks of age, and low levels of plasma progesterone, corticosterone, 180H-corticosterone and androstenedione were detectable. Testicular RNA for StAR was reverse transcribed, amplified, cloned and sequenced, revealing a 185 bp deletion corresponding to all of exon 5. The corresponding mRNA did not encode active protein in transfected cells. Cloned genomic DNA from the patient revealed only a T-->A transversion in intron 4,11 bp from the splice acceptor site of exon 5. This transversion destroys an NcoI site; digestion of PCR-amplified genomic DNA from the patient and both parents confirmed that the patient was homozygous and the parents were heterozygous. Expression vectors for StAR minigenes were constructed containing all StAR exons plus introns 4, 5 and 6 either with or without the T-->A mutation in intron 4. RNase protection assays showed that expression of the vector with normal intron 4 yielded correctly spliced StAR mRNA in transfected COS-1 cells, while most, but not all StAR mRNA from the vector with the T-->A transversion in intron 4 was abnormally spliced. RNase protection of the patient's testicular RNA confirmed that most, but not all StAR mRNA was similarly spliced abnormally. Splicing errors appear to be a rare cause of genetic diseases, but subtle intronic mutations may be missed when genomic DNA is the only material available for study. The low level of normal StAR mRNA produced may account for the later clinical presentation and low levels of steroid hormones detected in this patient.

Adrenal Hyperplasia, Congenital↗
PubMed1995

Efficiency of screening procedures for assigning levels of the Stanford Achievement Test (eighth edition) to students who are deaf or hard of hearing.

Assignment to an appropriate test level is crucial to the validity of standardized test scores. The present study examined the efficiency of the Reading Screening Tests and Mathematics Screening Tests developed by the Center for Assessment and Demographic Studies (CADS) of Gallaudet University for assigning levels of the Stanford Achievement Test, 8th edition (SAT-8), to deaf and hard-of-hearing students. Data were collected from programs participating in the 1990 test standardization with this population. It was found that while the screening procedures provide a credible means of assigning test levels, they are more effective for the SAT-8's Reading Comprehension, Total Language, Mathematics Computation, and Mathematics Applications subtests than for the Spelling and Concepts of Number subtests. This article concludes with recommendations in regard to individual subtest assignments.

Deafness↗
PubMed1994

The structure of the human sterol carrier protein X/sterol carrier protein 2 gene (SCP2).

Sterol carrier protein X (SCPx) is a 58-kDa protein that is localized to peroxisomes. The amino acid sequence of the protein suggests that SCPx may function as a thiolase. The gene encoding SCPx also codes for a 15.3-kDa protein called sterol carrier protein 2 (SCP2). Here we report the structure of this gene (SCP2), which spans approximately 80 kb and consists of 16 exons and 15 introns. Multiple transcription start sites were identified. The 5' flanking region has characteristics of other peroxisomal protein promoters, which include the absence of a TATA box and a G+C-enriched region containing several reverse GC boxes.

Acetyl-CoA C-Acetyltransferase↗
PubMed1994

CA-125 in peritoneal fluid from patients with nonmalignant gynecologic disorders.

To assess the diagnostic value of measuring CA-125 levels in peritoneal fluid from women with nonmalignant gynecologic disorders, we determined CA-125 levels in peritoneal fluid and in serum collected simultaneously from 46 women undergoing gynecologic surgery. Patients with benign ovarian disease, non-ovarian gynecologic pathology and severe endometriosis had, on average, higher CA-125 levels in peritoneal fluid than did patients with a normal pelvis and those with mild endometriosis. There was no obvious correlation between peritoneal fluid and serum levels of CA-125. Our data show that (1) measurement of serum CA-125 levels is not useful for distinguishing between different benign gynecologic disorders, and (2) levels of CA-125 in peritoneal fluid in benign gynecologic disorders are comparable to the reported lower range of levels observed in women with intraperitoneal malignancies.

Aftercare↗
PubMed1993

Rapid vascular escape of arterially injected 16 alpha-radioiodo,17 beta-estradiol.

PURPOSE: We undertook this study because confirmation of a rapid vascular escape and slow release back into the circulatory system suggests that arterial injection of radiohalogenated steroid receptor ligands might provide an efficacious route of administration for imaging or treatment of receptor-rich malignant tumors in peripheral tissues. METHODS AND MATERIALS: We injected radiolabeled 16 alpha-iodo,17 beta-estradiol ([I]-E), an estrogen receptor ligand, into the femoral artery of swine in a solution that contained [125I]-E in a known ratio to [99mTc]-labeled red blood cells. Fractions of femoral venous blood were collected at short intervals during 10 min. We looked for changes in the ratio of the radiolabels. [99mTc]-labeled red blood cells are known to remain in the vascular system for an hour or more. RESULTS: After passage of the injectate through the capillary bed of the swine leg, a dramatic decrease of the initial 125I:99mTc ratio to only 10% was observed in the femoral venous blood. This ratio increased gradually during the next 10 min to approximately 30% of that in the injectate, indicating that a significant portion (approximately 90%) of the [125I]-E was initially trapped in the limb and then slowly re-entered the vascular system. To obtain visual confirmation of the rapid vascular escape of iodo-estrogen, we injected either an imageable form of [I]-E (123I]-E) or [99mTc]-labeled red blood cells into the dorsal aorta of superovulated rabbits, whose smaller size allowed whole-body imaging. The biodistributions of these radiopharmaceuticals were surveyed continuously by real-time planar gamma imaging. Within 2 min after the injection of [123I]-E, the outlines of the circulatory system were entirely lost; however, some estrogen receptor-rich tissues (the ovaries) as well as some non-target tissues, for example, the lower leg extremities, yielded well-defined images. In contrast, after intra-arterial injection of [99mTc]-labeled red blood cells, the circulatory system remained sharply defined for the duration of the study (40 min). CONCLUSION: A large fraction of [I]-E escapes from the vascular system during the first pass through an organ or limb, without regard to the estrogen receptor content of the tissue.

Animals↗