Long-Term Seizure Freedom, Resolution of Epilepsy and Perceived Life Changes in Drug Resistant Temporal Lobe Epilepsy With Hippocampal Sclerosis: Comparison of Surgical Versus Medical Management.

BACKGROUND: Outcome of temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) has rarely been evaluated exclusively. OBJECTIVE: To compare long-term seizure freedom, resolution of epilepsy, and perceived life changes in patients with drug-resistant TLE-HS who underwent surgery vs those who opted for best medical management. METHODS: In this retrospective longitudinal study, 346 patients with TLE-HS who underwent surgery were compared with 325 who received best medical management. Predictors for long-term remission, resolution of epilepsy, and seizure recurrence were analyzed. RESULTS: The duration of follow-up ranged from 3-18 (mean 12.61) years. The average age of study population was 28.54 ± 12.27 years with 321 (47.8%) women. Age at onset of epilepsy (11.84 ± 8.48 vs 16.29 ± 11.88; P ≤ .001) was lower, and duration of epilepsy (15.65 ± 9.33 vs 12.97 ± 11.44; P < .001) was higher in the surgery group. Seizure freedom at 3 (81.8 vs 19.0%; P < .001), 5 (73% vs 16.1%; P < .001), and 10 years (78.3% vs 18.5; P < .001) and resolution of epilepsy (30.5% vs 0.6%; P < .001) was higher in the surgery group. The overall perceived life changes score was higher in the surgery group (80.96 ± 25.47 vs 66.24 ± 28.13; P < .001). At long-term follow-up (≥10 years), the presence of an aura was the strongest predictor for resolution of epilepsy (ß: 2.29 [95% CI; 1.06-4.93]; P = .035), whereas acute postoperative seizures (APOS) (ß: 6.06 [95% CI 1.57-23.42]; P < .001) and an abnormal postoperative EEG (ß: 0.222 [95% CI 0.100-0.491]; P < .001) were predictors of persistent seizures. Seizure freedom both at 3 and 5 years predicted seizure freedom at 10 years. CONCLUSION: Surgery for drug-resistant TLE-HS was associated with higher rate of long-term seizure-freedom, resolution of epilepsy, and reduction of anti-seizure medications with improvement in perceived life changes compared with best medical management. The presence of an aura was predictor for resolution of epilepsy while APOS and an abnormal postoperative EEG were predictors of persistent seizures.

Endoscopic Management of Lateral Ventricle Arachnoid Cysts-Case Series with Proposed Classification.

BACKGROUND: We present a case series of 7 patients with intraventricular arachnoid cysts of lateral ventricle managed with endoscopic treatment with proposed classification of the cyst based on anatomic extent. METHODS: In all patients, the lateral ventricle arachnoid cyst was primarily located in the trigone and body of the lateral ventricle. Proposed classification is based on extension of the arachnoid cyst. Type 1 is an arachnoid cyst located in the lateral ventricle only, type 2 is a lateral ventricle arachnoid cyst extending to the quadrigeminal cistern, and type 3 is the lateral ventricle arachnoid cyst extending to the velum interpositum cistern. RESULTS: Two patients were managed with multiple fenestration and septostomy, and in 1 patient where the cyst was not adherent to the ventricular wall it was excised completely. Two patients who had a lateral ventricle cyst located in the atrium but extending to quadrigeminal cyst were managed with 3 fenestrations. Two patients with a lateral ventricle arachnoid cyst located into the atrium of lateral ventricle and extending to the velum interpositum cistern through the choroid fissure were managed with 3 endoscopic fenestrations. Postoperatively, patients were followed clinically and by radiologic imaging. None of the patients reported recurrence until the latest follow-up. CONCLUSIONS: Multiple endoscopic fenestrations for lateral ventricle arachnoid cyst according to its location and anatomic extension help to reduce recurrence and good outcome. Cyst excision is recommended only when the cyst wall is easily separable from the lateral ventricle wall. Intraoperative use of thulium light amplification by stimulated emission of radiation helps in achieving early hemostasis and easy perforation of the thick cyst wall.

Contralateral Clipping of Multiple Intracranial Aneurysms.

The reported incidence of multiple intracranial aneurysms (MIA) is approximately 7-35% of all intracranial aneurysms. The primary goal in the management of MIAs is to secure the ruptured aneurysm and to treat as many of the remaining lesions as possible without affecting the outcome of the patient. In recent era endovascular treatment is the preferred treatment of multiple bilateral intracranial aneurysms if all aneurysms are amenable to addressed in single stage. But most often all aneurysms were not possible to addressed due to complexity of different aneurysms, technical limitation and infrastructure. In such scenarios options left were two stage sequential craniotomy on either sides and clipping of bilateral aneurysms or unilateral craniotomy and clipping of bilateral MIA. Bilateral two stage surgery or two stage endovascular treatment caries risk of bleeding from one of the untreated aneurysms, morbidity due to two stage and increase the cost of treatment. In properly selected cases of unilateral craniotomy and clipping of bilateral MIA secure the all aneurysm in one stage and decreased morbidity and cost of treatment. When patient selection done meticulously, clipping of MIA including contralateral side aneurysms is feasible and safe.

Avoiding Complications in Surgical Resection of Insular Gliomas - Single Surgeon Experience.

BACKGROUND AND AIMS: Insular gliomas remain one of most challenging locations for aggressive resection. We report our experience and strategies we employed to avoid complications in immediate post-operative period of surgical resection of insular gliomas. METHODS: Retrospective analysis of data collected in 61 consecutive patients who underwent surgical resection of insular gliomas between May 2013 and May 2016 was done. Primary outcome measures were neurological deficits and death in the immediate post-operative period to three months follow-up. RESULTS: The average age of the study population was 42.57 ± 10.98 years with 41 (67.2%) men. Glioma was on the right side in 35 (57.3%) patients. Surgery for recurrent glioma was performed in three (4.9%) patients. The average MIB index of the entire group was 10.1 ± 13.9. While 23 (37.7%) patients underwent the TO approach, 38 (62.3%) underwent TS approach. In the immediate post-operative period, significantly higher number of patients under TS approach had post-surgical complications (8.6% vs 34.2%; P = 0.032). The surgical approaches did not differ significantly for outcome, mortality and complications at three month post-operatively (0.0% vs 10.5%; P = 0.287). However, a trend for lower complications at three months was observed with TO approach. CONCLUSION: We report that morbidity and mortality in immediate post-operative period can be reduced by: a) pre-surgical assessment of confinement of glioma in respect to lenticulo-striate arteries, b) Intra-operative use of functional-MRI, DTI tractography and ICG angiography, c) Application of Berger-Sinai classification to localize the glioma, d) selecting either TS or TO approach based on Berger-Sinai classification.

Risk Stratification in Low Grade Glioma: A Single Institutional Experience.

BACKGROUND: Low grade gliomas (LGG) are most often noted with the unpredictable overall survival and progression to higher grades. Objective: In the present study, we analyze the clinicopathological features influencing the prognostic outcomes and compared the features with criteria developed by EORTC. MATERIALS AND METHODS: We observed the 130 LGG clinical cases in single institute and maintained the follow-up for more than 5 years. In addition, the molecular details were confirmed with markers as IDH, 1p/19q codeletion, p53 and ATRX mutations. RESULTS: The mean age of patients as 37.67 years and male population contributing to 70%. We observed biased incidence among the male population with dominating occurrence at frontal and parietal lobes in the brain. 40.8% patients had oligodendroglioma, 33.8% astrocytoma, 19.2% oligoastrocytoma and 2.3% gemistocytic astrocytoma pathology. Patients who were subjected to chemotherapy and radiotherapy were noted with average survival of 29 months. Oligodendroglial tumors were found with progression free survival (PFS) of 25 months, oligoastrocytoma cases with 32 months, diffuse astrocytoma cases with 23 months while the gemistocytic astrocytoma cases had 22 months. The PFS for LGG cases was 4.7 years while the overall survival was 4.9 years. Mean survival of patients with KPS score <70 and >70 was 1.5 & 4.9 years respectively. 64 patients were observed with the tumor size >5 cm. In total, 72.3% of the patients were underwent GTR, 23.3% STR and 3.8% underwent biopsy. CONCLUSION: Taken together, the clinical symptoms, expression of molecular markers and the prognosis details provided by our results can help for better management of LGG cases. We further propose to use following five factors to accurately describe the prognosis and tumor recurrence: 1) Age >50 years, 2) tumor size >5 cm, 3) MIB index >5%, 4) KPS score < 70 and 5) gemistocytic pathology.

Current Status of Surgery in Management of Prolactinomas.

Prolactinomas are a complex neuroendocrine challenge for the neurosurgeon. Management of prolactinoma patients requires centres that include neuroendocrinologists, neurosurgeons, neuroradiologists. Although dopamine agonists are the current mainstay of management of prolactinomas, surgery was often preferred management option prior to 1980, before the advent of dopamine agonists. Importantly, all patients with neurologic symptoms suspected due to the lesion, and those risk of adverse effects of medical management, treatment failure, resistance to dopamine agonists and those planning pregnancy, should be referred to a neurosurgeon at the earliest possible. When selected after meticulous evaluation, in patients with neurological deficits like acute visual loss, intolerance to medical therapy, or treatment failures, surgical intervention could come to rescue. Encouragingly, when carefully selected, surgical remission rates are high. In the current review, we review the existing literature and share the experience at our centre in the surgical management of prolactinomas.

Controversies in Diagnostic Imaging of Patients With Suspected Stable and Acute Chest Pain Syndromes.

There has been a tremendous growth quantity of high-quality imaging evidence in the area of acute and stable ischemic heart disease (SIHD). A number of recent comparative effectiveness trials have spurned significant controversies in the field of cardiovascular imaging. The result of this evidence is that many health care policies and national guidelines have undergone significant revisions. With all of this evidence, many challenges remain and the optimal evaluation strategy for evaluation of patients presenting with chest pain remains ill-defined. This paper enlisted the guidance of numerous experts in the field of cardiovascular imaging to garner their perspective on available imaging research in chest pain syndromes. Each of these vignettes represent editorial perspectives and diverse opinions as to which, if any, should be the primary test in the evaluation of stable chest pain. These perspectives are not meant to be all inclusive but to highlight many of the commonly discussed controversies in the evaluation of chest pain symptoms. These perspectives are presented as a pre-amble to an upcoming American College of Cardiology/American Heart Association clinical practice guideline that is undergoing revision from the previous report published in 2012. The evidence has changed considerably since the 2012 SIHD guideline, and the current perspectives represent the diversity of available evidence as to the optimal imaging strategy for evaluation of the symptomatic patient.

Gallic Acid Protects 6-OHDA Induced Neurotoxicity by Attenuating Oxidative Stress in Human Dopaminergic Cell Line.

Gallic acid is one of the most important polyphenolic compounds, which is considered an excellent free radical scavenger. 6-Hydroxydopamine (6-OHDA) is a neurotoxin, which has been implicated in mainly Parkinson's disease (PD). In this study, we investigated the molecular mechanism of the neuroprotective effects of gallic acid on 6-OHDA induced apoptosis in human dopaminergic cells, SH-SY5Y. Our results showed that 6-OHDA induced cytotoxicity in SH-SY5Y cells was suppressed by pre-treatment with gallic acid. The percentage of live cells (90%) was high in the pre-treatment of gallic acid when compared with 6-OHDA alone treated cell line. Moreover, gallic acid was very effective in attenuating the disruption of mitochondrial membrane potential, elevated levels of intracellular ROS and apoptotic cell death induced by 6-OHDA. Gallic acid also lowered the ratio of the pro-apoptotic Bax protein and the anti-apoptotic Bcl-2 protein in SH-SY5Y cells. 6-OHDA exposure was up-regulated caspase-3 and Keap-1 and, down-regulated Nrf2, BDNF and p-CREB, which were sufficiently reverted by gallic acid pre-treatment. These findings indicate that gallic acid is able to protect the neuronal cells against 6-OHDA induced injury and proved that gallic acid might potentially serve as an agent for prevention of several human neurodegenerative diseases caused by oxidative stress and apoptosis.

Antidepressant like effects of hydrolysable tannins of Terminalia catappa leaf extract via modulation of hippocampal plasticity and regulation of monoamine neurotransmitters subjected to chronic mild stress (CMS).

Terminalia catappa L. belonging to Combretaceae family is a folk medicine, known for its multiple pharmacological properties, but the neuro-modulatory effect of TC against chronic mild stress was seldom explored. The present study was designed to elucidate potential antidepressant-like effect of Terminalia cattapa (leaf) hydro-alcoholic extract (TC) by using CMS model for a period of 7 weeks. Identification of hydrolysable tannins was done by using LC-MS. After the CMS exposure, mice groups were administered with imipramine (IMP, 10mg/kg, i.p.) and TC (25, 50 and 100mg/kg of TC, p.o.). Behavioural paradigms used for the study included forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT). After behavioural tests, monoamine neurotransmitter, cortisol, AchE, oxidative stress levels and mRNA expression studies relevant to depression were assessed. TC supplementation significantly reversed CMS induced immobility time in FST and other behavioural paradigms. Moreover, TC administration significantly restored CMS induced changes in concentrations of hippocampal neurotransmitters (5-HT, DA and NE) as well as levels of acetyl cholinesterase, cortisol, monoamine oxidases (MAO-A, MAO-B), BDNF, CREB, and p-CREB. It suggests that TC supplementation could supress stress induced depression by regulating monoamine neurotransmitters, CREB, BDNF, cortisol, AchE level as well as by amelioration of oxidative stress. Hence TC can be used as a complementary medicine against depression-like disorder.

Surgical Resection of Insular Gliomas and Roles of Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging Tractography-Single Surgeon Experience.

OBJECTIVE: In gliomas located in proximity to eloquent areas, near total resection and subsequent radiotherapy is often preferred to avoid postoperative neurologic complications. Preoperative functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) tractography provide new insights into surgeries of insular gliomas. In this study we report our experience of surgical management of insular gliomas and the role of fMRI and DTI tractography in planning the resection. METHODS: We retrospectively compared the clinical and outcome variables of 61 patients who underwent surgical resection of insular gliomas. The study population was divided into 2 groups according to the use of fMRI and DTI tractography in planning the resection. RESULTS: The average age of the study population was 44.1 ± 12.6 years with 21 (34.4%) of the patients women. Nearly two thirds of them (40, or 65.6%) had World Health Organization grade II tumors, and 16 patients (26.2%) had grade IV tumors. The most common tumor was glioblastoma, observed in 16 patients (26.2%). In 10 (16.4%) patients, fMRI and DTI tractography were used. The overall mortality in the study population was 15 (24.6%). None of the patients where fMRI and DTI were used for planning the surgery died (29.4% vs. 0.0%; P = 0.05), and all of them had normal functioning (70.5% vs. 100.0%; P = 0.05) at 3 months' follow-up. CONCLUSION: Surgical resection of insular gliomas remains a challenge to the neurosurgeon and demands good knowledge of anatomic landmarks. Use of fMRI and DTI tractography may help achieve a good outcome.

Apoptosis in heart failure: a tale of heightened expectations, unfulfilled promises and broken hearts em leader.

Although apoptosis contributes significantly to remodeling of the fetal heart during evolution of cardiac chambers and correct routing of the great vessels, it has been believed that apoptosis does not occur in terminally differentiated adult cardiac muscle cells. However, apoptosis has recently been demonstrated in animal models of heart failure as well as in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation. Ventricular dilatation and neurohormonal activation, the hall-marks of heart failure, lead to upregulation of transcription factors, induce muscle cell hypertrophy and prepare cells for entry into the cell-division cycle. However, since terminally differentiated myocytes cannot divide, they die by apoptosis. It has been proposed that low-grade apoptosis in failing heart may be responsible for inexorable decline in left ventricular function. Better understanding of the molecular and cellular basis of apoptosis in the failing myocardium may lead to development of strategies aimed at preventing progressive myocyte loss and deterioration in left ventricular function.

Increased bioactive luteinizing hormone levels in postmenopausal women with endometrial cancer.

OBJECTIVE: The purpose of our study was to investigate the secretion of immunoactive and bioactive luteinizing hormone in postmenopausal women with endometrial cancer. STUDY DESIGN: Seventeen postmenopausal women with endometrial cancer and nine without cancer were studied. Blood samples were collected at 15-minute intervals for 360 minutes. All samples were assayed for bioactive luteinizing hormone by rat interstitial cell testosterone assay and for immunoactive luteinizing hormone by radioimmunoassay. Serum pooled from 6-hour sampling was assayed for follicle-stimulating hormone, total estradiol, unbound estradiol, and estrone. RESULTS: Patients with endometrial cancer had significantly (p < 0.01) higher bioactive luteinizing hormone levels (mean +/- SE 276 +/- 26 IU/L) as compared with those of control women (144 +/- 18 IU/L). Bioactive/immunoactive ratios of luteinizing hormone were significantly higher (p < 0.01) in women with cancer (5.8 +/- 0.7) than in those without cancer (2.5 +/- 0.5). There was a significant (p < 0.001) positive correlation (r = 0.582) between unbound estradiol levels and bioactive luteinizing hormone concentrations. CONCLUSIONS: There is an increase in bioactive luteinizing hormone secretion in postmenopausal women with endometrial cancer. This could lead to an increase in ovarian androgen production resulting in increased prehormone availability for estrogen formation from peripheral conversion.

Insulin-like growth factor I and II binding in human myometrium and leiomyomas.

OBJECTIVES: The purpose of this study is to determine if the human myometrium has receptors for insulin-like growth factors I and II and whether the concentration of these receptors is increased in leiomyomas. STUDY DESIGN: Specific binding of iodine 125-labeled insulin-like growth factor I and II was examined in the membrane preparations of myometrium and leiomyomas obtained from 10 women with uterine leiomyomas. RESULTS: Binding studies indicate presence of specific binding sites for both insulin-like growth factors I and II in the myometrium and leiomyoma. The concentration of binding sites for insulin-like growth factor I, but not for insulin-like growth factor II, was significantly (p less than 0.01) higher in leiomyomas than in the myometrium. The dissociation constants for insulin-like growth factors I and II receptors in both myometrium and leiomyoma were similar. CONCLUSION: insulin-like growth factor I, but not insulin-like growth factor II, receptors are increased in leiomyomas compared with those in myometrium, indicating that insulin-like growth factor I may play a role in the generation and/or growth of this tumor.

Effects of the antiandrogen hydroxyflutamide on progesterone secretion by preovulatory rat follicles in vivo and in vitro.

Serum and ovarian progesterone levels and in vitro production of progesterone by preovulatory follicles were measured on proestrus in pregnant mare's serum gonadotropin (PMSG) primed immature rats in which the luteinizing hormone (LH) surge and ovulation were blocked by administration of the antiandrogen hydroxyflutamide. Serum progesterone levels observed at 12:00 on proestrus were significantly elevated, twofold above those observed in vehicle-treated controls, by in vivo administration of 5 mg hydroxyflutamide 4 h earlier. In control rats, proestrous progesterone did not increase until 16:00, in parallel with rising LH levels of the LH surge. No LH surge occurred in the hydroxyflutamide-treated rats, ovulation was blocked, and serum progesterone declined throughout the afternoon of proestrus, from the elevated levels present at 12:00. Administration of human chorionic gonadotropin (hCG) at 11:00 advanced the elevation of serum progesterone by 2 h in vehicle-treated controls and prevented the decline in progesterone levels in hydroxyflutamide-treated rats. The patterns of change in ovarian tissue concentrations with time and treatment were essentially similar to those observed for serum progesterone. In in vitro experiments, progesterone secretion during 24 h culture of preovulatory follicles obtained on PMSG-induced proestrus was significantly increased, sixfold, by addition to the culture media of 370 microM but not of 37 microM hydroxyflutamide. Testosterone (50 nM) and hCG (20 mIU/mL) caused 26- and 14-fold increases, respectively, in progesterone secretion by cultured follicles. Hydroxyflutamide significantly reduced the stimulatory effect of testosterone but not of hCG on progesterone secretion in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of uterine progesterone receptors by the nonsteroidal anti-androgen hydroxyflutamide.

We have recently reported that the anti-androgen hydroxyflutamide causes delayed implantation and exhibits antideciduogenic activity in the rat. The present experiments were conducted to examine whether hydroxyflutamide binds to the uterine progesterone receptors and/or alters the progesterone binding sites in the uterus. Cytosol and nuclear fractions from decidualized rat uterus were incubated with [3H]-R5020 without or with increasing concentrations of radioinert R5020, RU486, dihydrotestosterone, or hydroxyflutamide. From the log-dose inhibition curves, the relative binding affinity of both hydroxyflutamide and dihydrotestosterone was less than 0.1% and 2%, compared with R5020 (100%) for displacing [3H]-R5020 bound to uterine cytosol and nuclear fractions, respectively. Injection of estradiol-17 beta (1 microgram/rat) to ovariectomized prepubertal rats induced a 1.85-fold increase in uterine weight by 24 h. Hydroxyflutamide at 2.5 or 5.0 mg did not significantly alter the estrogen-induced increase in uterine weight. Compared to vehicle alone, estrogen induced an approximately 5-fold increase in uterine cytosolic progesterone binding sites. Hydroxyflutamide at both 2.5- and 5.0-mg doses significantly attenuated the estrogen-induced elevation in uterine progesterone binding sites. These studies demonstrate that hydroxyflutamide does not bind with high affinity to progesterone receptors, but suppresses the estrogen-induced elevation in progesterone receptor levels in the uterus.

Receptors for insulin-like growth factor II in the rat uterus: characterization and variation throughout the estrus cycle.

This study was undertaken to identify uterine insulin-like growth factor II receptors and examine the regulation of these receptor levels throughout the estrus cycle. We have demonstrated IGF-II receptors in crude uterine membranes by binding and cross-linking experiments. IGF-II binding to the rat uterine membranes displayed time and temperature dependence and maximum binding was achieved by 2 h at 22 degrees C. Uterine IGF-II binding sites were specific for binding IGF-II peptide and demonstrated negligible binding affinity for IGF-I and no affinity for insulin. The specific anti-IGF-II receptor antibody, R-II-PAB1, blocked the specific [125I]IGF-II binding to uterine membranes in a dose-dependent manner. The characteristics of uterine IGF-II receptor are similar to those reported for other tissues, with a single class of high-affinity binding sites with an apparent dissociation constant of 1.2 +/- 0.5 nmol/l and Beta max of 2.65 +/- 0.41 pmol/mg protein. Affinity cross-linking experiments indicated that the specific binding of [125I]IGF-II in the uterus is associated with a single band of protein with a mol wt of 250 kD. In mature cycling rats, the proestrus uterus had the lowest level of [125I]IGF-II binding per mg membrane protein, without changes in receptor affinity. However, because of greater yield of protein from proestrus uteri, the total [125I]IGF-II binding capacity of the uterus was similar to the other stages of the estrus cycle. These studies demonstrate the presence of authentic IGF-II receptors in the rat uterus and illustrate variations in the concentration of these receptors in the uterus throughout the estrus cycle.

Effects of hydroxyflutamide on female reproductive function.

PIP: Among the observed effects of hydroxyflutamide (HF), a nonsteroidal anti-androgenic drug, are blockade of ovulation and the preovulatory luteinizing hormone (LH) surge and delay in implantation and suppressed decidualization of the uterus. HF binds to the androgen receptor and competitively inhibits the binding of testosterone and dihydrotestosterone. As a nonsteroidal compound, HF is devoid of other hormonal or anti-hormonal activities and thus can be used for the investigation of the role of androgens in various reproductive processes. In female rats, HF has been demonstrated to overcome the ovulation inhibitory effect of a high LH: follicle stimulating hormone (FSH) ratio and to block the LH surge. Since HF is not anti-estrogenic, the suppressed HF surge in HF-treated rates is not due to interference with estradiol-mediated positive feedback. There are indications, however, that HF does interfere with progesterone action in induction of the LH surge and thus may have an anti-progestagenic activity. In prepubertal rats, HF exhibits anti-progestagenic action at the level of the uterus and cervix as well as the hypothalamus. This function appears related to HF's ability to bind to progesterone receptors and reduce receptor levels. Injection of HF significantly enhances the estradiol-induced elevation in rat's uterine progesterone binding sites yet does not affect uterine growth response. It is hypothesized that HF interferes with the ability of estrogen to induce progesterone receptors at a post-receptor site, but further research is needed to identify the mechanisms involved.^ieng

Binding of insulin-like growth factor-I to rat uterus; variations during sensitization and decidualization.

IGF-I receptors have been identified and characterized in a variety of tissues. In this study receptors for IGF-I in the rat uterine tissue were identified and characterized. We have demonstrated IGF-I receptors in crude uterine membranes by binding and cross-linking experiments. IGF-I binding to the rat uterine membranes displayed time, temperature and pH dependance, and optimal binding conditions were achieved by 20 h of incubation at 4 degrees C, at a pH of 7.8. Uterine IGF-I binding sites were specific for binding IGF-I peptide and demonstrated less than 100 x lower affinity for insulin. The binding was reversible and Scatchard analysis indicated presence of a single class of binding sites with an apparent dissociation constant of 1.68 +/- 0.24 nmol/l and Bmax of 0.82 +/- 0.1 pmol/mg protein. During estrogen treatment, sensitization and decidualization there was an overall increase of membrane proteins in the uterus and a relative decrease of IGF-I receptors per unit of protein. When expressed on a per uterus basis, there was a progressive increment in total IGF-I binding in estradiol-treated, sensitized, and decidualized uterus compared with controls. These data indicate a possible role for IGF-I in uterine cell multiplication and further differentiation to decidual cells in response to deciduogenic stimuli.