Definitions matter: detection rates and perinatal outcome for infants classified prenatally as having late fetal growth restriction using SMFM biometric vs ISUOG/Delphi consensus criteria.

OBJECTIVES: Fetal growth restriction (FGR) is often secondary to placental dysfunction and is suspected prenatally based on biometric or circulatory abnormalities detected on ultrasound. The aims of this study were to compare the screening performance of the Society for Maternal-Fetal Medicine (SMFM) biometric criteria (estimated fetal weight (EFW) or abdominal circumference (AC) < 10th centile) with that of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG)-endorsed Delphi consensus criteria for late FGR for delivery of a small-for-gestational-age (SGA) infant at term, emergency Cesarean section (CS) for non-reassuring fetal status (NRFS), perinatal mortality and composite severe neonatal morbidity. METHODS: We classified retrospectively non-anomalous singleton infants as having late FGR (diagnosed ≥ 32 weeks) according to SMFM and ISUOG/Delphi criteria in a cohort of women who had been referred to the Mater Mother's Hospital, Brisbane, Australia and who delivered at term between January 2014 and December 2020. The study outcomes were delivery of a SGA infant (birth weight (BW) < 10th or < 3rd centile), emergency CS for NRFS, perinatal mortality (defined as stillbirth or neonatal death within 28 days of a live birth) and a composite of severe neonatal morbidity. We assessed the screening performance of various ultrasound variables by calculating the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, false-positive and false-negative rates, positive likelihood ratio (LR+) and negative likelihood ratio. RESULTS: The SMFM and ISUOG/Delphi consensus criteria collectively classified 1030 cases as having late FGR. Of these, 400 cases were classified by both SMFM and ISUOG/Delphi criteria, whilst 548 cases were classified using only SMFM criteria and 82 cases were classified only by ISUOG/Delphi criteria. Prenatal detection of late FGR by SMFM and ISUOG/Delphi criteria was associated with increased odds of delivery of an infant with BW < 10th centile (SMFM: adjusted odds ratio (aOR), 133.0 (95% CI, 94.7-186.6); ISUOG/Delphi: aOR, 69.5 (95% CI, 49.1-98.2)) or BW < 3rd centile (SMFM: aOR, 348.7 (95% CI, 242.6-501.2); ISUOG/Delphi: aOR, 215.4 (95% CI, 148.4-312.7)). Compared with the SMFM criteria, the ISUOG/Delphi criteria were associated with lower odds (aOR, 0.5 (95% CI, 0.3-0.8)) of predicting a SGA infant with BW < 10th centile, but higher odds of predicting emergency CS for NRFS (aOR, 2.30 (95% CI, 1.14-4.66)) and composite neonatal morbidity (aOR, 1.22 (95% CI, 1.05-1.41)). Both SMFM and ISUOG/Delphi criteria were associated with high LR+, specificity, PPV and NPV for the prediction of infants with BW < 10th and BW < 3rd centile. However, both methods functioned much less efficiently for the prediction of composite severe neonatal morbidity or emergency CS for NRFS, with LR+ < 10. The SMFM biometric criteria alone, particularly AC < 3rd centile, had the highest LR+ values for the prediction of perinatal mortality. CONCLUSION: Both the SMFM and ISUOG/Delphi criteria had strong screening potential for the detection of infants with BW < 10th or < 3rd centile but not for adverse neonatal outcome. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Expanding functions of ADP-ribosylation in the maintenance of genome integrity.

Cell response to genotoxic stress requires a complex network of sensors and effectors from numerous signaling and repair pathways, among them the nuclear poly(ADP-ribose) polymerase 1 (PARP1) plays a central role. PARP1 is catalytically activated in the setting of DNA breaks. It uses NAD+ as a donor and catalyses the synthesis and subsequent covalent attachment of branched ADP-ribose polymers onto itself and various acceptor proteins to promote repair. Its inhibition is now considered as an efficient therapeutic strategy to potentiate the cytotoxic effect of chemotherapy and radiation or to exploit synthetic lethality in tumours with defective homologous recombination mediated repair. Still, efforts made on understanding the role of PARylation in DNA repair continues to yield novel discoveries. Over the last years, our knowledge in this field has been particularly advanced by the discovery of novel biochemical and functional properties featuring PARP1, by the characterization of the other PARP family members and by the identification of a panel of enzymes capable of erasing poly(ADP-ribose). The aim of this review is to provide an overview of these newest findings and their relevance in genome surveillance.

Colonic microbiota can promote rapid local improvement of murine colitis by thioguanine independently of T lymphocytes and host metabolism.

OBJECTIVE: Mercaptopurine (MP) and pro-drug azathioprine are 'first-line' oral therapies for maintaining remission in IBD. It is believed that their pharmacodynamic action is due to a slow cumulative decrease in activated lymphocytes homing to inflamed gut. We examined the role of host metabolism, lymphocytes and microbiome for the amelioration of colitis by the related thioguanine (TG). DESIGN: C57Bl/6 mice with or without specific genes altered to elucidate mechanisms responsible for TG's actions were treated daily with oral or intrarectal TG, MP or water. Disease activity was scored daily. At sacrifice, colonic histology, cytokine message, caecal luminal and mucosal microbiomes were analysed. RESULTS: Oral and intrarectal TG but not MP rapidly ameliorated spontaneous chronic colitis in Winnie mice (point mutation in Muc2 secretory mucin). TG ameliorated dextran sodium sulfate-induced chronic colitis in wild-type (WT) mice and in mice lacking T and B lymphocytes. Remarkably, colitis improved without immunosuppressive effects in the absence of host hypoxanthine (guanine) phosphoribosyltransferase (Hprt)-mediated conversion of TG to active drug, the thioguanine nucleotides (TGN). Colonic bacteria converted TG and less so MP to TGN, consistent with intestinal bacterial conversion of TG to so reduce inflammation in the mice lacking host Hprt. TG rapidly induced autophagic flux in epithelial, macrophage and WT but not Hprt-/- fibroblast cell lines and augmented epithelial intracellular bacterial killing. CONCLUSIONS: Treatment by TG is not necessarily dependent on the adaptive immune system. TG is a more efficacious treatment than MP in Winnie spontaneous colitis. Rapid local bacterial conversion of TG correlated with decreased intestinal inflammation and immune activation.

[The role of PARP2 in DNA repair].

The genome stability of higher eukaryotes is mainly dependent on the functioning of the DNA repair systems. In turn, the precise regulation of each step of repair processes is required for efficient DNA repair. While at present the most pathways of DNA repair have been established already, but the mechanisms of DNA repair regulation are required further investigation. Poly(ADP-ribose)polymerases (PARPs) are widely considered as potential regulators of a DNA repair. The role of most prominent member of this protein family--PARP1--in DNA repair is intensively studied, while the literature data on participation in repair processes of PARP2--the closestPARP1 homolog--are poorly Sum- marized although a great body of information concerning PARP2 participation in DNA repair has accumulated.. Using PARP2-deficient model organisms and cell lines, their increased sensitivity to several DNA damage agents was elucidated. The accumulation of PARP2 at the DNA damage sites in cells was shown. There are data demonstrating protein-protein interaction of PARP2 with several base excision repair/single strand break repair and non-homologous end joining proteins. Most of the data on PARP2 role have been obtained in experiments with model organisms and cell lines so it is difficult to project the attribution of PARP2 influence to specific process in vivo. In this review, we tried to summarize data on PARP2 participation in DNA repair processes, including our recent results.

Recurrent intrahepatic dislocation of ventriculoperitoneal shunt.

BACKGROUND: Dislocation of ventriculoperitoneal (VP) shunt catheters is a well known complication after treatment of cerebrospinal fluid disorders; however, secondary perforation of the liver capsule by the catheter is exceptional. The literature on VP shunt complications involving the liver, their possible pathomechanisms and minimally invasive recovery strategies in reference to our own experience is reviewed. CASE REPORT: We present a patient who suffered penetration of the liver by the peritoneal catheter of her VP shunt. Causing intermittent epigastric pain, the shunt tip was found to have progressively dislocated into the liver, as documented by CT scans. A laparoscopic approach was indicated to recover the shunt. The peritoneal catheter was found to be covered by widespread adhesions, consistent with peritoneal fibrosis. After local adhesiolysis, it was successfully recovered without shunt dysfunction, hemorrhage of the liver, or biliary fistula. After 4 months, dislocation recurred with formation of a subdiaphragmatic pseudocapsule. Early formation of fibrosis was detected during laparoscopic revision surgery. Although bacterial smears from both laparoscopic surgeries did not show any pathological findings, the patient presented with an abscess in the Douglas pouch 4 months later. Coagulase-negative staphylococci were found on ultrasound-guided insertion of a pigtail catheter. The VP shunt had to be replaced by a ventriculoatrial shunt. The infection was treated successfully with piperacillin. The subsequent 6 months follow-up period was without adverse events. CONCLUSION: The treatment of choice in this exceptional case of intrahepatic shunt dislocation was laparoscopic recovery of the catheter. Laparoscopy allowed good visualization during adhesiolysis, immediate exclusion of hemorrhage or bile fistula at the puncture site, as well as function control and safe deposition of the shunt tip. Chronic infection as an underlying cause of peritoneal fibrosis has to be ruled out.

No significant effect of orally administered chemokine receptor 1 antagonist on intercellular adhesion molecule-3 expression in relapsing--remitting multiple sclerosis patients.

We investigated the expression of intercellular adhesion molecules ICAM-1 and ICAM-3 on peripheral blood mononuclear cells in a subgroup of 34 patients with relapsing-remitting multiple sclerosis who were treated orally with the chemokine receptor 1 antagonist BX 471 in a 16-week, randomised, double-blind, placebo-controlled phase II study. ICAM-1 and ICAM-3 expression was measured by flow cytometry at different time points during and after therapy and compared using multivariate analysis of variance and non-parametric Mann Whitney test. ICAM-3 expression on CD14( +) peripheral blood mononuclear cells was increased in the verum group under therapy, but did not differ significantly between the verum and placebo groups. Most likely, this trend represents a small epiphenomenon only mediated by receptor cross-talk and feedback mechanisms.

Targeting of adenovirus vectors carrying a tumor cell-specific peptide: in vitro and in vivo studies.

Previously, we have identified a tumor cell-specific peptide, HEW, by panning of phage display libraries on the human colorectal cancer cell line WiDr. In this report we demonstrate that this peptide can modify the infection properties of adenovirus vectors. Increased infectivity of replication-deficient adenovirus 5 vectors in WiDr cells was observed upon genetic insertion of the HEW peptide in the HI loop of the fiber knob. Moreover, whereas the coxsackie and adenovirus receptor (CAR)-ablating fiber mutation S408E abolished apparent infection in CAR-positive WiDr cells, the insertion of HEW completely restored infectivity toward these cells in vitro. To assess whether the de- and re-targeted infection profile was maintained in vivo, the fiber-modified adenovirus vectors were injected intratumorally or intravenously in WiDr tumor-bearing Swiss nu/nu mice. No significant differences in efficiency of infection could be observed suggesting alternative viral uptake mechanisms in vivo. Next, we have included the fiber shaft mutation S(*) in our studies, which was described to confer a de-targeted phenotype in vivo. Reduced gene transfer due to the S(*) mutation both in vitro and in vivo could be confirmed. Insertion of HEW in the HI knob loop of shaft-mutated fiber, however, did not rescue infectivity in target cells neither in vitro nor in vivo. We demonstrate the efficient ligand-mediated re-targeting of adenoviral vector infection to the human cancer cell line WiDr. The lack of apparent re-targeting in the in vivo situation is described.

XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage.

Poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) is a zinc-finger DNA-binding protein that detects and signals DNA strand breaks generated directly or indirectly by genotoxic agents. In response to these breaks, the immediate poly(ADP-ribosyl)ation of nuclear proteins involved in chromatin architecture and DNA metabolism converts DNA damage into intracellular signals that can activate DNA repair programs or cell death options. To have greater insight into the physiological function of this enzyme, we have used the two-hybrid system to find genes encoding proteins putatively interacting with PARP. We have identified a physical association between PARP and the base excision repair (BER) protein XRCC1 (X-ray repair cross-complementing 1) in the Saccharomyces cerevisiae system, which was further confirmed to exist in mammalian cells. XRCC1 interacts with PARP by its central region (amino acids 301 to 402), which contains a BRCT (BRCA1 C terminus) module, a widespread motif in DNA repair and DNA damage-responsive cell cycle checkpoint proteins. Overexpression of XRCC1 in Cos-7 or HeLa cells dramatically decreases PARP activity in vivo, reinforcing the potential protective function of PARP at DNA breaks. Given that XRCC1 is also associated with DNA ligase III via a second BRCT module and with DNA polymerase beta, our results provide strong evidence that PARP is a member of a BER multiprotein complex involved in the detection of DNA interruptions and possibly in the recruitment of XRCC1 and its partners for efficient processing of these breaks in a coordinated manner. The modular organizations of these interactors, associated with small conserved domains, may contribute to increasing the efficiency of the overall pathway.

[Laparoscopic Janeway gastrostomy: an advantageous solution for self-sufficient enteral feeding]. / Gastrostomie tubulisée coelioscopique : une solution avantageuse pour une nutrition entérale autonome.

INTRODUCTION: Laparoscopic gastrostomy according to Janeway (LGJ) is an alternative to percutaneous gastrostomy techniques. METHODS: A series of 10 LGJ is reported. The laparoscopic technique involves an isoperistaltic tube of 6-7 cm of length and 10-12 mm of diameter is created by 2 applications of linear stapling and cutting device. The tube is led out, opened and fixed to the fascial and cutaneous planes and a Foley catheter is inserted. RESULTS: Mean operation time was 35 minutes. There was no complication. The LGJ was indicated in 9 patients with tumour of the pharynx and 1 patient with encephalopathy. CONCLUSION: The main drawback of the LGJ is the need of general anaesthesia. The main advantage is the creation by minimal invasive surgery of a permanent gastrostomy equipped with a removable catheter easily changeable by non specialized health professionals, and even by the patient himself.

[Two 150 years anniversaries: Claude Bernard's internal environment and Addison disease]. / Dve stopadesátiletá výrocí: Claude Bernardovo vnitrní prostredí a Addisonova nemoc.

In 2005 two 150 years anniversaries, which essentially influenced the development of modern medicine will be celebrated. French physiologist Claude Bernard from College de France published his work "Lectures on Experimental Physiology, applied to medicine" and British medical doctor T. Addison described insufficiency of adrenal cortex, today known as Addison disease.

PARP-2 sustains erythropoiesis in mice by limiting replicative stress in erythroid progenitors.

Erythropoiesis is a tightly regulated process in which multipotential hematopoietic stem cells produce mature red blood cells. Here we show that deletion of poly(ADP-ribose) polymerase-2 (PARP-2) in mice leads to chronic anemia at steady state, despite increased erythropoietin plasma levels, a phenomenon not observed in mice lacking PARP-1. Loss of PARP-2 causes shortened lifespan of erythrocytes and impaired differentiation of erythroid progenitors. In erythroblasts, PARP-2 deficiency triggers replicative stress, as indicated by the presence of micronuclei, the accumulation of γ-H2AX (phospho-histone H2AX) in S-phase cells and constitutive CHK1 and replication protein A phosphorylation. Transcriptome analyses revealed the activation of the p53-dependent DNA-damage response pathways in PARP-2-deficient cells, culminating in the upregulation of cell-cycle and cell death regulators, concomitant with G2/M arrest and apoptosis. Strikingly, while loss of the proapoptotic p53 target gene Puma restored hematocrit levels in the PARP-2-deficient mice, loss of the cell-cycle regulator and CDK inhibitor p21 leads to perinatal death by exacerbating impaired fetal liver erythropoiesis in PARP-2-deficient embryos. Although the anemia displayed by PARP-2-deficient mice is compatible with life, mice die rapidly when exposed to stress-induced enhanced hemolysis. Our results pinpoint an essential role for PARP-2 in erythropoiesis by limiting replicative stress that becomes essential in the absence of p21 and in the context of enhanced hemolysis, highlighting the potential effect that might arise from the design and use of PARP inhibitors that specifically inactivate PARP proteins.

A eukaryotic expression vector for the study of nuclear localization signals.

We describe a new vector designed to produce beta-galactosidase fusion proteins which can be used to assess subcellular localization of target peptide fragments or proteins in eukaryotic cells. The vector was constructed in such a way as to produce the peptide of interest in fusion via a short linker of proline residues to the N terminus of the reporter protein. Efficiency of the transport machinery is optimized using this particular protein fusion construction. This vector has potential uses for readily testing putative nuclear localization sequences and identifying their crucial amino-acid residues.

Chromosomal assignment and expression pattern of the murine Lasp-1 gene.

The human Lasp-1 (LIM and SH3 protein) gene was previously identified by differential screening of a breast cancer-derived metastatic lymph node cDNA library. It was located on the q12-q21 region of human chromosome 17 and was shown to be amplified and overexpressed in 12% of breast tumors. Lasp-1 defines a new LIM-protein subfamily, as it associates a C-terminal Src homology 3 (SH3) domain to a N-terminal LIM motif. In this study, the isolation and characterization of the cDNA encoding the mouse Lasp-1 protein are described, and it is shown to be highly conserved with its human counterpart. In addition to the LIM and SH3 domains, both human and mouse Lasp-1 contain an actin-binding domain. The mouse gene was mapped by in situ hybridization to the 11C-11D region of chromosome 11. Northern blot analysis shows that this gene is expressed from 7.5 to 17.5 days post-coitum of mouse embryogenesis and in almost all adult tissues.

Lasp-1 (MLN 50) defines a new LIM protein subfamily characterized by the association of LIM and SH3 domains.

MLN 50 was previously identified in a cDNA library of breast cancer metastasis. In this study, we show that MLN 50, which is expressed at a basal level in normal tissues, is overexpressed in 8% of human breast carcinomas most often together with c-erbB-2. MLN 50 cDNA encodes a putative protein of 261 residues, named Lasp-1 (LIM and SH3 protein) since it contains a LIM motif and a domain of Src homology region 3 (SH3) at the amino- and the C-terminal parts of the protein, respectively. Thus, Lasp-1 defines a new LIM protein subfamily.

Poly(ADP-ribose) polymerase: structure-function relationship.

Dissection of the human poly(ADP-ribose) polymerase (PARP) molecule in terms of its structure-function relationship has proved to be an essential step towards understanding the biological role of poly(ADP-ribosylation) as a cellular response to DNA damage in eukaryotes. Current approaches aimed at elucidating the implication of this multifunctional enzyme in the maintenance of the genomic integrity will be presented.

Involvement of poly(ADP-ribose) polymerase in base excision repair.

Poly(ADP-ribose) polymerase (PARP) is a zinc-finger DNA binding protein that detects and signals DNA strand breaks generated directly or indirectly by genotoxic agents. In response to these lesions, the immediate poly(ADP-ribosylation) of nuclear proteins converts DNA interruptions into intracellular signals that activate DNA repair or cell death programs. To elucidate the biological function of PARP in vivo, the mouse PARP gene was inactivated by homologous recombination to generate mice lacking a functional PARP gene. PARP knockout mice and the derived mouse embryonic fibroblasts (MEFs) were acutely sensitive to monofunctional alkylating agents and gamma-irradiation demonstrating that PARP is involved in recovery from DNA damage that triggers the base excision repair (BER) process. To address the issue of the role of PARP in BER, the ability of PARP-deficient mammalian cell extracts to repair a single abasic site present on a circular duplex plasmid molecule was tested in a standard in vitro repair assay. The results clearly demonstrate, for the first time, the involvement of PARP in the DNA synthesis step of the base excision repair process.

Estrogenic effect of estradiol-sulfamate on the male rat anterior pituitary.

Estrogen sulfamates (ES) are used for a new treatment strategy to avoid liver-hormone and hormone-liver interactions. ES represent new synthetic steroids having an increased systemic and reduced hepatic estrogenicity when given orally [1,2]. In the present study effects of ES and estradiol-benzoate (EB) on adenohypophyseal (AP) and serum concentrations of prolactin (PRL), luteinizing hormone (LH), and pituitary contents of cAMP and cGMP in the male rat are demonstrated. The weight gain of experimental animals treated by ES, EB or both hormones simultaneously was significantly lower compared to controls. EB but not ES significantly increased the weight of the AP. The amounts of PRL in the AP and serum were significantly increased after EB administration. ES significantly increased only AP content of PRL. EB administered simultaneously with ES exhibited an additive effect on the AP plasma concentrations of PRL. The EB or ES significantly decreased AP and serum concentrations of LH. ES given simultaneously with EB further decreased AP and serum concentrations of LH. After administration of either ES or EB, AP contents of cAMP and cGMP were significantly increased. An additive effect of these estrogens on the cGMP content was found. ES given simultaneously with EB further increased cGMP content in the AP but partially inhibited the effect of EB on the AP cAMP content. The present results demonstrate that the effects of ES on the AP content of PRL, LH, cAMP, and cGMP differ from the effects of EB. Whether this is due to lower levels of estradiol after the administration of ES secondary to its different absorption when compared to EB is unknown. Thus, our data support the concept that the ES has a lesser estrogenic effect on the AP function.

Early and delayed effects of hydrocortisone and onapristone on intestinal brush-border enzymes and their sialylation and on thymus growth in suckling rats.

The antigestagen-antiglucocorticoid onapristone (ZK 98.299) was tested on three glucocorticoid-sensitive systems after hydrocortisone (HC) administration to suckling male rats, by determining onapristone (ZK)-induced inhibition of HC-provoked (1) increase of activities of intestinal brush-border enzymes, (2) desialylation of brush-border components and (3) thymolysis. HC acetate (75 mg/kg body weight (b.w.)) was injected s.c. on postnatal days 9 and 10, and ZK (150 mg/kg b.w.) on days 9, 10 and 11. The animals were killed on day 12 for assessing the early effect, or on days 15-17 for determining the delayed effect of HC and ZK. In all three systems the glucocorticoid effects were antagonized by ZK. The most sensitive to HC were systems 1 and 3, which exhibited both the early and the delayed effects. The most sensitive to the counteraction of ZK against administered HC was system 1, where HC was antagonized in both its early and delayed effects, whereas only delayed antagonistic action against administered HC was found in system 2. ZK alone had an early inhibitory effect on the activities of several brush-border enzymes and produced an early increase in thymus weight, accompanied by an increased DNA-protein ratio. No delayed effects of ZK alone on the three systems were observed.

Cytoreductive surgery and intraperitoneal chemohyperthermia for peritoneal carcinomatosis arising from gastric cancer.

HYPOTHESIS: The most common cause of palliative resection and recurrence in gastric cancer is peritoneal seeding. This study evaluates the efficacy of intraperitoneal chemohyperthermia after cytoreductive surgery in patients with peritoneal carcinomatosis arising from gastric cancer. DESIGN: Prospective clinical trial. SETTING: Surgical department at a university academic hospital. PATIENTS: Forty-nine consecutive patients with peritoneal carcinomatosis treated between January 1, 1989, and February 29, 2000. INTERVENTIONS: All patients underwent intraperitoneal chemohyperthermia with mitomycin C (40-60 mg); 21 patients had previously undergone extensive cytoreductive surgery. MAIN OUTCOME MEASURES: Clinicopathologic factors that affect overall survival rates. RESULTS: With median follow-up of 99 months, overall median survival was 10.3 months. Two factors were significant independent predictors of survival by multivariate analysis: preoperative ascites (P =.04) and completeness of cancer resection (CCR) by cytoreductive surgery (P<.001). Median survival was 21.3 months for patients with CCR-0 (macroscopic complete resection) or CCR-1 (diameter of residual nodules <5 mm) and 6.1 months for patients with CCR-2 (diameter of residual nodules >5 mm) (P<.001). Four patients survived longer than 5 years. CONCLUSIONS: An aggressive management strategy combining intraperitoneal chemohyperthermia with cytoreductive surgery is effective for patients with peritoneal carcinomatosis arising from gastric cancer. In highly selected patients (good general status, resectable primary tumor, resectable peritoneal carcinomatosis), this therapy may result in long-term survival.

Triiodothyronine attenuates estradiol-induced increases in dopamine D-2 receptor number in rat anterior pituitary.

Estrogens promote adenohypophyseal enlargement and tumor transformation, and thyroid hormones antagonize these effects. Hormone-induced pituitary enlargement may be mediated by alterations in pituitary dopaminergic function. The present study examined the effects of chronic (20 days) administration of estradiol benzoate (EB), triiodothyronine (T3), or EB and T3 (T3 + EB) on dopamine (D-2) receptors in rat anterior pituitary. D-2 receptor number increased after EB without altered receptor affinity. T3 alone did not affect D-2 receptor number in the anterior pituitary but significantly attenuated the effect of EB. T3 administration also inhibited EB-induced anterior pituitary hyperplasia. D-2 receptor upregulation by EB more likely could reflect a compensatory response to decreased receptor occupation. The present results suggest that D-2 receptors could play an important role in estrogen-induced adenohypophyseal tumor formation and hyperprolactinemia and that thyroid hormones may inhibit estrogen-induced pituitary tumor development via adenohypophyseal D-2 receptors.