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PubMed2001

Fibrocartilage in the transverse ligament of the human atlas.

STUDY DESIGN: Immunohistochemical investigation. OBJECTIVE: To determine whether molecules typical of articular cartilage are present in the transverse ligament and whether the ligament may be a target for an autoimmune response in rheumatoid arthritis. SUMMARY OF BACKGROUND DATA: In chronic rheumatoid arthritis there is often a marked instability of the atlantoaxial complex, and the transverse ligament can show degenerative changes that compromise its mechanical function. In some rheumatoid patients there can be an autoimmune response to cartilage link protein, aggrecan, and Type II collagen. METHODS: Transverse ligaments were removed from 13 cadavers and fixed in 90% methanol. Cryosections were immunolabeled with antibodies against proteoglycans (aggrecan, link protein, and versican), glycosaminoglycans (chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, and keratan sulfate), and collagens (Types I, II, III, and VI). RESULTS: Labeling for aggrecan and link protein was characteristic of the fibrocartilages, but versican was only detected in the fibrous regions. Equally, Types I, III, and VI collagens and keratan, dermatan, and chondroitin-4-sulfates were found throughout the ligament, but labeling for Type II collagen and chondroitin-6-sulfate was restricted to the fibrocartilages. CONCLUSION: The presence of molecules typical of articular cartilage (aggrecan, link protein, and Type II collagen) in the transverse ligament explains why it can be a target for destruction in rheumatoid arthritis and also suggests that it is subject to constant compression against the dens rather than only at the extremes of movement.

Aged↗

PubMed2026

A pan-cancer analysis of MEX3D in human tumors.

BACKGROUND: MEX3D, a member of the MEX3 RNA-binding protein family, has emerged as a potential regulatory molecule in cancer. However, its role across different tumor types remains largely unexplored. METHODS: We conducted a pan-cancer analysis of MEX3D using transcriptomic and proteomic data from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Expression patterns, clinical correlations, survival outcomes, genetic alterations, RNA modification associations, immune infiltration, and functional enrichment were systematically evaluated. RESULTS: MEX3D was significantly dysregulated in numerous cancers at both mRNA and protein levels. Its expression correlated with tumor stage in ACC, LIHC, OV, SKCM, and THCA. Elevated MEX3D expression was associated with poor overall survival (OS) and disease-specific survival (DSS) in multiple malignancies, including ACC, LGG, LUAD, and MESO. Genetic alteration analysis revealed frequent amplifications and mutations, particularly in SARC and OV. MEX3D was positively correlated with RNA modification-related genes (m1A, m5C, m6A) and immune regulatory genes such as CD276, TGFB1, VEGFA, and ICOSLG. Additionally, MEX3D expression showed significant associations with tumor mutational burden (TMB), microsatellite instability (MSI), and cancer-associated fibroblast infiltration. Functional enrichment analyses indicated that MEX3D-related genes are involved in reproductive cellular processes, RNA binding, the Hippo signaling pathway, and microRNA-related oncogenic pathways. CONCLUSION: This pan-cancer analysis highlights the heterogeneous expression and cancer-specific prognostic significance of MEX3D. MEX3D is associated with immune infiltration, immune regulatory genes, RNA modification-related genes, TMB/MSI, and pathways involved in gene regulation and tumor progression. These findings suggest that MEX3D may participate in cancer-specific post-transcriptional and microenvironmental regulatory networks.

Biomarker↗

PubMed2026

Decoding the landscape of cell-type-specific co-expressed transcription factors in soybean.

Soybean (Glycine max) is an essential source of protein and oil with high nutritional value for human and animal consumption. To enhance our understanding of soybean biology, it is essential to have accurate information regarding the expression of each of its protein-coding genes. Here, we present Tabula Glycine max, a soybean single-cell resolution transcriptome atlas. This atlas comprises single-nucleus RNA-sequencing data from ten different G. max organs and morphological structures constituting the entire soybean plant. These nuclei are grouped into 156 different clusters based on their transcriptomic profiles. The breadth of various organs, tissues and cell types represented in Tabula Glycine max reveals that the pattern of co-expressed transcription factor genes is sufficient to define most cell types based on their function and organ of origin. Defining cell-type-specific co-expressed transcription factor genes offers a new perspective to engineer cell-type-specific programmes and enhance the biology of unique soybean cell types. This cellular resolution and breadth make the Tabula Glycine max an exceptional resource for the plant and soybean communities.

Journal Article↗

PubMed2002

A potential role of heat shock proteins and nicotinamide N-methyl transferase in predicting response to radiation in bladder cancer.

The use of definitive radiotherapy for treatment of invasive bladder cancer has the advantage of preserving bladder function, but tumour regression is only achieved in approximately 40-50% of patients. Knowledge of the molecular basis of sensitivity to ionizing radiation and identification of potential molecular predictors will provide useful information regarding patient response and thus help clinicians to individualize treatment. The recent application of cDNA expression array technology provides a useful tool to investigate hundreds or even thousands of genes in a single experiment. In our study, we have used the Atlas human stress cDNA array trade mark to investigate the expression profile of stress-related and DNA repair genes in a radioresistant bladder carcinoma cell line (MGH-U1) and its radiosensitive subclone (S40b). This provides an ideal situation to study genes related to radiation because the genotypes of both cell lines are basically similar and differential changes detected are likely to be related to the different radiosensitivity phenotype. Of 234 genes blotted on the array, 3 genes (Heat shock protein 90, Heat shock protein 27 and Nicotinamide N-methyl transferase) showed consistent downregulation in the radiosensitive clone in 2 independent experiments. These results were further confirmed for HSP27 and NNMT using Sybr Green I-based real-time QRT-PCR. The role of heat shock proteins (HSPs) in response to radiation remains to be determined; however, the results of our present work suggest a possible role of HSP27 in determining radiosensitivity. Our study also opens avenues for the investigation of genes, such as NNMT, which has not previously been linked to response to radiation.

Base Sequence↗

PubMed1998

Antibodies from ALS patients inhibit dopamine release mediated by L-type calcium channels.

OBJECTIVE: To examine the presence of anti-L-type calcium channel antibodies in the serum of ALS patients. BACKGROUND: Autoimmunity has been hypothesized as one of the mechanisms underlying the pathogenesis of sporadic ALS. Previous studies reported that sera from patients with sporadic ALS contain antibodies against voltage-gated calcium channels (L-type and P-type), but others do not support these findings. METHODS: Regulated secretion of tritiated dopamine ([3H]DA) in PC12 cells is mediated exclusively by calcium entry through L-type calcium channels. To examine whether purified ALS immunoglobulin G (IgG) inhibits [3H]DA release by interfering with calcium entry through L-type calcium channels, evoked release in PC12 cells was determined in the presence of ALS IgG. This functional assay provides a sensitive way to examine L-type calcium channel interaction with IgG from ALS patients. RESULTS: A significant inhibition of depolarization-evoked [3H]DA release (32+/-4%) was observed by purified IgG from ALS patients compared with control subjects (11+/-2%; p < 0.01). Significant inhibition by IgG occurred in 79% (15/19) of the ALS patients compared with only 29% (5/17) in the control group (p < 0.01). The level of calcium channel inhibition by ALS IgG correlated positively with disease duration (r = 0.68; p < 0.01) and correlated negatively with age (r = -0.48; p < 0.05). CONCLUSIONS: These results confirm the presence of antibodies against the L-type calcium channel in the majority of sera from ALS patients, supporting their role in the pathogenesis of ALS.

Amyotrophic Lateral Sclerosis↗

PubMed2026

Mapping cell-type- and age-dependent neuronal vulnerability through genome-wide in vivo CRISPRi screens in the mouse brain.

Current brain atlases are largely descriptive, cataloging correlative molecular snapshots such as gene expression signatures yet offering limited functional insight. Here, we develop a scalable, cell-type-resolved in vivo CRISPR interference (CRISPRi) platform enabling systematic gene function profiling in the mouse brain. Through genome-wide screens across four neuronal populations at three time points spanning youth to aging, we identify neuronal essential genes missed in vitro and define a consensus set of 269 neuronal core essential genes. The data reveal cell-type-specific genetic vulnerabilities, including divergent dependencies validated for exosome component 9 (Exosc9) and osteopetrosis-associated transmembrane protein 1 (Ostm1) between excitatory and inhibitory neurons. We uncover aging-specific dependencies enriched in mitochondrial and translational pathways, aligning with transcriptional changes in the aging human brain. Finally, we establish the CRISPRinvivo data portal as a community resource for in vivo screening. Altogether, this work provides a broadly applicable platform for in vivo functional genomics and a framework for building comprehensive gene-function brain atlases.

brain aging↗

PubMed2004

Tumor cells are present in stem cell harvests of Ewings sarcoma patients and their persistence following transplantation is associated with relapse.

BACKGROUND: Tumor cells frequently contaminate autologous stem cell products in a variety of malignancies, but their clinical significance remains controversial. We retrospectively monitored tumor contamination in stem cell harvests from patients with Ewing family of tumors (EFT) all harboring the specific translocation EWS-FLI-1 that characterize these tumors. PROCEDURE: Twenty- seven harvests from 11 patients were included in the study. In addition, 6 and 19 bone marrow (BM) or peripheral blood (PBL) samples were available before and after transplantation, respectively, for RT-PCR and nested PCR analyzes. RESULTS: All 11 patients had contaminating tumor cells in their harvests. All samples prior to transplantation were RT-PCR positive. Two out of the 11 patients who underwent transplantation died of complications. Out of the remaining nine patients, two are alive and well 68 and 84 months from diagnosis, and are the only patients with no detectable tumor cells in their samples after transplantation. One of these patients harbored contaminating tumor cells in only one of the two harvests collected. Seven patients relapsed after transplant, and in four patients BM/PBL samples were available prior to the clinical relapse. All these samples harbored contaminating tumor cells. CONCLUSIONS: We suggest a possible correlation between the amount of contaminating cells in the harvest and relapse after transplantation. Quantitative RT-PCR studies of the chimeric transcripts are underway to explore this issue.

Adolescent↗

PubMed1991

A new family of powerful multivariate statistical sequence analysis techniques.

A novel multivariate statistical approach is presented for extracting and exploiting intrinsic information present in our ever-growing sequence data banks. The information extraction from the sequences avoids the pitfalls of intersequence alignment by analyzing secondary invariant functions derived from the sequences in the data bank rather than the sequences themselves. Such typical invariant function is a 20 x 20 histogram of occurrences of amino acid pairs in a given sequence or fragment thereof. To illustrate the potential of the approach an analysis of 10,000 protein sequences from the National Biomedical Research Foundation Protein Identification Resource is presented, whose analysis already reveals great biological detail. For example, zeta-hemoglobin is found to lie close to amphibian and fish chi-hemoglobin which, in turn, is an important clue to the physiological function of this mammalian early embryonic hemoglobin. The multivariate statistical framework presented unifies such apparently unrelated issues as phylogenetic comparisons between a set of sequences and distance matrices between the constituents of the biological sequences. The Multivariate Statistical Sequence Analysis (MSSA) principles can be used for a wide spectrum of sequence analysis problems such as: assignment of family memberships to new sequences, validation of new incoming sequences to be entered into the database, prediction of structure from sequence, discrimination of coding from non-coding DNA regions, and automatic generation of an atlas of protein or DNA sequences. The MSSA techniques represent a self-contained approach to learning continuously and automatically from the growing stream of new sequences. The MSSA approach is particularly likely to play a significant role in major sequencing efforts such as the human genome project.

Amino Acid Sequence↗

PubMed2004

Array-based analysis of gene expression in childhood acute lymphoblastic leukemia.

Gene expression profiles of 10 children with acute lymphoblastic leukemia (ALL) were detected using cDNA arrays. Total RNAs were isolated from peripheral blood leukocytes of the patients at diagnosis. For detection of expression profiles we used Atlas Human Cancer cDNA Arrays (Clontech) with 588 genes. Although the study revealed variability of gene expression in many genes, we identified a number of genes with the same expression changes (up-regulation: PCNA, ERCC1; down-regulation: jun-B, BCL-2 related protein A1, CRAF-1, PBP) in most examined patients. Our objective was to identify genes that were differentially expressed in ALL and might contribute to development (and characterization) of the disease.

Adolescent↗

PubMed1998

Cloning and sequence analysis of four t(9;11) therapy-related leukemia breakpoints.

The t(9;11)(p22;q23) is the most common chromosomal translocation in topoisomerase II inhibitor therapy-related acute myeloid leukemia (tAML). This translocation fuses the MLL and AF9 proto-oncogenes producing a novel chimeric protein. In order to gain insight into the mechanism generating the t(9;11) and to clarify the role topoisomerase II inhibition may play in that mechanism we have cloned and sequenced the breakpoints from four tAML patients with the t(9;11). This sequence analysis identifies topoisomerase II consensus binding sequences near or at the chromosome 11 and chromosome 9 breakpoints in all four patients. One patient also had the consensus binding sequence for the TRANSLIN DNA-binding protein at the 9p22 and 11q23 breakpoints. Our results further support a direct role for topoisomerase II in the genesis of these tAML translocations.

Acute Disease↗

PubMed2025

Rhythm profiling using COFE reveals multi-omic circadian rhythms in human cancers in vivo.

The study of ubiquitous circadian rhythms in human physiology requires regular measurements across time. Repeated sampling of the different internal tissues that house circadian clocks is both practically and ethically infeasible. Here, we present a novel unsupervised machine learning approach (COFE) that can use single high-throughput omics samples (without time labels) from individuals to reconstruct circadian rhythms across cohorts. COFE can simultaneously assign time labels to samples and identify rhythmic data features used for temporal reconstruction, while also detecting invalid orderings. With COFE, we discovered widespread de novo circadian gene expression rhythms in 11 different human adenocarcinomas using data from The Cancer Genome Atlas (TCGA) database. The arrangement of peak times of core clock gene expression was conserved across cancers and resembled a healthy functional clock except for the mistiming of a few key genes. Moreover, rhythms in the transcriptome were strongly associated with the cancer-relevant proteome. The rhythmic genes and proteins common to all cancers were involved in metabolism and the cell cycle. Although these rhythms were synchronized with the cell cycle in many cancers, they were uncoupled with clocks in healthy matched tissue. The targets of most of FDA-approved and potential anti-cancer drugs were rhythmic in tumor tissue with different amplitudes and peak times. These findings emphasize the utility of considering "time" in cancer therapy, and suggest a focus on clocks in healthy tissue rather than free-running clocks in cancer tissue. Our approach thus creates new opportunities to repurpose data without time labels to study circadian rhythms.

Humans↗

PubMed2001

Fibrocartilage in the transverse ligament of the human acetabulum.

Biomechanical experiments on isolated hip joints have suggested that the transverse ligament acts as a bridle for the lunate articular surface of the acetabulum during load bearing, but there are inherent limitations in such studies because the specimens are fixed artificially to testing devices and there are no modifying influences of muscle pull. Further evidence is thus needed to substantiate the theory. Here we argue that if the horns of the lunate surface are forced apart under load, the ligament would straighten and become compressed against the femoral head. It would thus be expected to share some of the features of tendons and ligaments that wrap around bony pulleys and yet previous work has suggested that the transverse ligament is purely fibrous. Transverse ligaments were removed from 8 cadavers (aged 17-39 y) and fixed in 90% methanol. Cryosections were immunolabelled with antibodies against collagens (types I, II, III, VI), glycosaminoglycans (chondroitins 4 and 6 sulphate, dermatan sulphate, keratan sulphate) and proteoglycans (aggrecan, link protein, versican, tenascin). A small sesamoid fibrocartilage was consistently present in the centre of each transverse ligament, near its inner surface at the site where it faced the femoral head. Additionally, a more prominent enthesis fibrocartilage was found at both bony attachments. All fibrocartilage regions, in at least some specimens, labelled for type II collagen, chondroitin 6 sulphate, aggrecan and link protein, molecules more typically associated with articular cartilage. The results suggest that the ligament should be classed as containing a 'moderately cartilaginous' sesamoid fibrocartilage, adapted to withstanding compression. This supports the inferences that can be drawn from previous biomechanical studies. We cannot give any quantitative estimate of the levels of compression experienced. All that can be said is that the ligament occupies an intermediate position in the spectrum of fibrocartilaginous tissues. It is more cartilaginous than some wrap-around tendons at the wrist, but less cartilaginous than certain other wrap-around ligaments, e.g. the transverse ligament of the atlas.

Acetabulum↗

PubMed2000

RARbeta involvement in enhancement of lung tumor cell immunogenicity revealed by array analysis.

The retinoid receptors (RARs and RXRs) are mediators of the multiple effects of retinoic acid. Of these, the retinoic acid receptor beta2 (RARbeta2) has frequently been shown to be the principal mediator of the growth and tumor suppressive effects of retinoic acid; this gene is inactivated in many epithelial tumors and their derived cell lines. We have searched for genes that are regulated by this isoform and are potentially involved in tumor suppression. Using the Atlas human cDNA array I, we identified 27 genes (not counting RARbeta itself) that are regulated, directly or indirectly, by RARbeta2 when it is transfected into Calu-1, a lung tumor-derived line that does not normally express RARbeta. Several of the affected genes code for proteins whose functions would augment the process of apoptosis and/or the host's immune response. The latter group included ICAM-1 and MHC class I heavy chain, whose protein products play particularly important roles in the mounting of an effective anti-tumor response. We then confirmed by flow cytometry that the observed increases in message levels were reflected in increased cell surface protein levels for ICAM-1 and MHC class I in RARbeta2 transfectants of two RARbeta-deficient lines, Calu-1 and the epidermoid lung cancer-derived line SK-MES. Finally, we showed that RARbeta2 transfection of Calu-1 cells enhanced the heterologous CTL response in both the induction and the effector phases by up to threefold. These results support the hypothesis that down-regulation of these genes (and possibly others) in RARbeta-deficient tumor cells contributes to immune system evasion, and suggest a novel therapeutic approach for this disease.

Apoptosis↗

PubMed1990

Relation of blood viscosity to demographic and physiologic variables and to cardiovascular risk factors in apparently normal adults.

Although increased blood viscosity occurs in several cardiovascular diseases, little is known of factors influencing blood rheology in normal adults. Accordingly, we examined the relations of whole blood viscosity (WBV) to its rheologic determinants (hematocrit level, plasma viscosity, protein concentration, and red cell aggregability and rigidity), to demographic and laboratory variables, and to cardiovascular risk factors in 128 normotensive employed adults. Hematocrit levels accounted for 67-84% of variability of WBV at shear rates from 208 to 0.1 sec-1 with lesser contributions from plasma viscosity, red cell aggregability, and rigidity (multiple r = 0.95-0.97); WBV was predicted accurately from standard measurements of hematocrit and total plasma protein levels (multiple r = 0.78-0.92 in "learning" and "test" analysis). Male sex, obesity, dietary Na+ intake, and increasing age had additive effects on WBV (multiple r greater than or equal to 0.59, p less than 0.00001); the last three of these factors and black race independently predicted plasma viscosity (multiple r = 0.36, p less than 0.001). Among regulators of plasma volume, plasma renin activity and urinary Na+ excretion bore independent positive relations to WBV. Diastolic and mean blood pressures were independent predictors of WBV and hematocrit levels (all p less than 0.05). Conventional risk factors (e.g., triglycerides, obesity, and cholesterol levels) were positively related to WBV or plasma viscosity. Thus, in apparently normal adults, 1) WBV or plasma viscosity are increased by male sex, obesity, high sodium intake, aging, and black race, 2) WBV is positively related to plasma renin activity, 3) WBV or plasma viscosity are related to diastolic and mean blood pressures, triglycerides and cholesterol concentrations, and 4) WBV can be predicted from simple measurements of hematocrit and total plasma protein levels.

Adult↗

PubMed1999

Gene Expression Profiles of Human Fetal Nasopharyngeal Tissue.

To study differentially expressed genes in nasopharynx tissues of embryo during development, and to observe the gene changes, total RNAs were respectively extracted from the nasopharynx tissue which came from fetuses of 5, 6, 7, and 8 month, Probes were yielded by reverse transcription and were used to hybridize with the Atlas(TM) human cDNA expression arrays. The results showed that the genes expression profile were distinctly different and different expression levels were found in the same gene during development. Results indicated that gene expression pattern had a character of time-dependence, such as early growth response protein 1 and the cDNA expression array provided a powerful method for studying gene expression profile in a large range of genes.

Journal Article↗

PubMed2004

Differential gene expression in human hepatocellular carcinoma Hep3B cells induced by apoptosis-related gene BNIPL-2.

AIM: Bcl-2/adenovirus E1B 19 ku interacting protein 2-like (BNIPL-2) is a novel protein recently identified in our laboratory. BNIPL-2 is homologous to human BNIP-2, a potentially proapoptotic protein, and can interact with Bcl-2 and Cdc42GAP and promote apoptosis in BEL-7402 cells. Here we report the gene-expression profile regulated by BNIPL-2 in human hepatocarcinoma Hep3B cells and the analysis of its potential roles in cell apoptosis. METHODS: BNIPL-2 was overexpressed in Hep3B cells using tetracycline inducible or Tet-on system. Screened by Western blot, the cells with low background and high induction fold of BNIPL-2 were obtained. We performed Atlas human cDNA expression array hybridization on these cells and analyzed the data with Quantarray software to identify BNIPL-2-regulated genes and their expression profile. RT-PCR was used to confirm the altered expression level of part of genes identified by the Atlas array hybridization. RESULTS: Fifteen of 588 genes spotted on the Atlas membrane showed altered expression levels in BNIPL-2-transfected Hep3B-Tet-on cells, in which 8 genes involved in cell apoptosis or growth inhibition were up-regulated and 7 genes involved in cellular proliferation were down-regulated following overexpression of BNIPL-2. CONCLUSION: cDNA array is a powerful tool to explore gene expression profiles under inducible conditions. The data obtained using the cDNA expression microarray technology indicates that BNIPL-2 may play its roles in apoptosis through regulating the expression of genes associated with cell apoptosis, growth inhibition and cell proliferation.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Uterine retiform sertoli-leydig cell tumor: report of a case providing additional evidence that uterine tumors resembling ovarian sex cord tumors have a histologic and immunohistochemical phenotype of genuine sex cord tumors.

We report a case of a retiform Sertoli-Leydig cell tumor of intermediate differentiation presenting as a uterine intracavity polypoid mass in a 63-year-old woman. In contrast to sertoliform endometrioid carcinoma and to hitherto reported uterine tumors resembling ovarian sex cord tumors (UTROSCTs), which are primarily characterized by tubular glands and solid tubules, this tumor, which most likely represents a UTROSCT, showed a large spectrum of histologic features typical of a genuine retiform Sertoli-Leydig cell tumor. The diagnosis was confirmed by a battery of immunohistochemical stains, which also served as a tool for differential diagnosis with other neoplasms. The tumor cells were positive for broad spectrum keratin (CK) CK18, vimentin, calretinin, and progesterone receptor. Only a few isolated cells stained for inhibin. The tumor cells were negative for CK7, CK5/6, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), thrombomodulin, 013 (CD99), melan A, alpha-fetoprotein (AFP), placental alkaline phosphatase (PLAP), alpha-1-antitrypsin, estrogen receptor, S100, neurone specific enolase (NSE), chromogranin, synaptophysin, desmin, caldesmon, and CD10. Divergent differentiation of uterine cells seems to be the most likely pathogenetic mechanism. To the best of our knowledge, no UTROSCT showing such a variety of histologic features indicative of a true sex cord tumor has been reported before.

Calbindin 2↗

PubMed1987

Ovarian prorenin.

We review here recent evidence that the ovaries synthesize and secrete prorenin and we explore the possible reasons why prorenin, and not active renin, is formed almost exclusively in this extra-renal site. Very high concentrations of prorenin are present in the human ovary in the fluid inside mature follicles. This ovarian prorenin appears to be secreted into the circulation since plasma prorenin increases in normal women for two to three days at mid-menstrual cycle, at the time of ovulation. No change in plasma active renin occurs at this time. Plasma prorenin increases much more at mid-cycle in women whose ovaries have been hyperstimulated with gonadotropins. Their mid-cycle increment in plasma prorenin (after hCG) is directly related to the number of ovarian follicles. Plasma prorenin also increases markedly (10-fold) in pregnant women within two weeks after conception, in parallel with the rise in endogenous hCG. The ovaries are the apparent source of the increase in plasma prorenin during pregnancy since no such increase occurred in a woman with ovarian failure who conceived after receiving a donor egg. These results suggest that the ovaries synthesize and secrete prorenin in response to stimulation by gonadotropic hormones. Future studies will investigate the potential role of ovarian prorenin in human reproductive function. We postulate the existence of a prorenin receptor which activates prorenin and, in consequence, activates a local renin-angiotensin system. The functioning of this system may be regulated by changes in prorenin and its receptor.

Animals↗