Biomedical subjects

P Petrusz

Publications and source records attributed to P Petrusz.

At least 19 recordsLinked to original sources

PubMed2005

Androgen-binding protein is co-expressed with oxytocin in the male reproductive tract.

Androgen-binding protein (ABP) and the posterior lobe hormone oxytocin (OT) were co-localized in male rat reproductive organs. Immunostaining of serial semi-thin sections revealed a high rate of coexistence of both antigens in Sertoli cells and in the epithelial cells of the prostate. There was a considerably less co-localization of OT and ABP in epithelial cells of the epididymis, and in the different tissues of the ductus deferens. In situ hybridization with synthetic oligonucleotides complementary to a fragment of ABP mRNA showed specific staining in the same sites that were immunostained for ABP. ABP was isolated by affinity chromatography from homogenates of testis, epididymis, prostate and the content of the prostate lumen. Identical protein patterns could be shown with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry in all samples except for the epididymis indicating that ABP structure is similar in all these tissues. ABP seems to be expressed in specified cells throughout the male rat reproductive tract. Most of these cells appear to be oxytocinergic. ABP and OT have previously been detected in the ejaculate. The observed epithelial cells are likely to be their source.

Androgen-Binding Protein↗

PubMed2004

Hormonal regulation of human trophoblast differentiation: a possible role for 17beta-estradiol and GnRH.

We have examined the role of 17beta-estradiol and gonadotropin releasing hormone (GnRH) in the regulation of functional differentiation in human trophoblasts. In contrast to its recognized functions as a proliferation-promoting hormone in a variety of cell types, we found that 17beta-estradiol induced terminal differentiation in human trophoblastic cells, and that this event was estrogen-receptor-mediated. This process involved a loss in expression of Cyclins A2 and E, and a coincident increase in p27(Kip1). The anti-proliferative effects of 17beta-estradiol were annulled by specific transforming growth factor-beta 1 (TGFbeta1)-neutralizing antibody, suggesting that 17beta-estradiol may mediate its growth-inhibitory actions, through TGFbeta1 activity. Following exposure to Buserelin, cultured human trophoblastic cells stopped proliferating and formed functionally mature syncytiotrophoblasts. This differentiation event, that involved a drastic loss in expression of proliferating-cell-nuclear-antigen, could be blocked by Cetrorelix, suggesting the involvement of functional GnRH receptors. Preliminary studies on the characterization of the human placental GnRH receptor, indicate the presence of multiple receptor isoforms across human gestation.

Animals↗

PubMed2002

Dynamics of testicular germ cell proliferation in normal mice and transgenic mice overexpressing rat androgen-binding protein: a flow cytometric evaluation.

Transgenic mice carrying rat androgen-binding protein (ABP) genomic DNA express high amounts of testicular ABP and develop a progressive impairment of spermatogenesis. To understand the mechanism of these changes, we have studied the pattern of testicular germ cell proliferation from 7 to 360 days of age in wild-type (WT) control and transgenic homozygous (ABP-TG) mice by flow cytometry after labeling DNA in isolated germ cells with propidium iodide. At all ages studied, the body weight of the ABP-TG mice was lower than that of age-matched WT controls. Significantly reduced testicular weight and total germ cell number in the ABP-TG mice were evident from Day 30 and Day 60, respectively. Flow cytometric analysis of isolated germ cells revealed that the number of germ cells undergoing proliferation (S-phase cells) was identical in WT control and ABP-TG mice up to Day 14. Subsequently, the number of germ cells in S-phase was consistently higher in ABP-TG than in WT mice. The number of primary spermatocytes was significantly increased starting from Day 60, and the numbers of round and elongated spermatids were significantly reduced in the ABP-TG animals from Day 21 and Day 60 onwards, respectively. Immunocytometry for intracellular ABP at 90 days of age revealed that the percentage of ABP-containing germ cells was greater in ABP-TG than in WT mice. The continuous presence of ABP in mouse seminiferous tubules at greater than physiological concentrations facilitates the formation of primary spermatocytes but impairs subsequent transformation to round and elongated spermatids. Based on our observations and the analysis of the available literature, the most likely mechanism for production of these effects is sustained reduction in the bioavailability of androgens.

Aging↗

PubMed2001

Oxytocin receptors in non-human primate brain visualized with monoclonal antibody.

The identity of putative oxytocin receptors visualized in autoradiographic studies of primate brain is unclear because the ligand used is much less selective in primate than rodent brains. This study tests the feasibility of utilizing a new monoclonal antibody (MoAb) developed against human uterine OTRs to visualize OTRs in primate brain. A block containing ventral hypothalamus of cynomolgus macaque brain, paraformaldehyde, glutaraldehyde-fixed and paraffin-embedded, and positive control tissue (human endometrium) were sectioned at 8 microm and studied with immunohistochemistry. OTRs were located in fibers in septal nucleus and in both cell bodies and fibers of preoptic area. These results indicate that OTRs in primate brain may be visualized with this MoAb, and are located in primate brain sites linked to the regulation of social behavior.

Animals↗

PubMed2001

Immunohistochemical localization of nitric oxide synthase and soluble guanylyl cyclase in the ventral cochlear nucleus of the rat.

The diffusible messenger nitric oxide (NO) is implicated in auditory processing. It acts in the brain largely through activation of soluble guanylyl cyclase (sGC), a heterodimer comprised of alpha and beta subunits. The authors used immunohistochemistry to study the NO/guanosine 3',5'-cyclic monophosphate (cGMP) pathway in the cochlear nucleus of Sprague-Dawley rats. Central fibers of the cochlear nerve were stained for neuronal nitric oxide synthase (NOS-I) but not for sGCbeta. Within the ventral cochlear nucleus, a large fraction of principal cells were immunopositive for both NOS-I and sGCbeta; these cells could be seen at times receiving contacts from NOS-I-positive fibers. sGC staining of somatic cytoplasm extended into the distal dendritic tree. At variance with this pattern, NOS-I was concentrated mainly in somata. Double-labeling experiments showed that most of the principal neurons expressed both antigens. By contrast, in the granule cell domain, small cells that were immunopositive for NOS-I rarely corresponded to those that were immunopositive for sGC. To assess whether NOS-I and sGC immunoreactivities colocalize with their respective catalytic activities, the authors performed multiple labeling with L-citrulline (a by-product of the formation of NO from L-arginine) and cGMP, respectively. L-citrulline was restricted to NOS-I-positive elements, and the large majority of NOS-expressing neurons were positive for citrulline. Multiple labeling revealed that almost all sGC-positive neurons also accumulated cGMP both in the ventral cochlear nucleus and in the granule cell domain. These data suggest that NO is a signaling molecule in the cochlear nucleus, perhaps functioning in both a paracrine manner and an autocrine manner.

Animals↗

PubMed2001

Primate epididymis-specific proteins: characterization of ESC42, a novel protein containing a trefoil-like motif in monkey and human.

Epididymal secreted proteins promote sperm maturation and fertilizing capacity by interacting with sperm during passage through the epididymis. Here we investigate the molecular basis of sperm maturation by isolating cDNA clones for novel epididymis-specific expressed sequences. Thirty-six novel cDNAs were isolated and sequenced from a subtracted Macaca mulatta epididymis library. The clones encode proteins with a range of motifs characteristic of protein-modifying enzymes, protease inhibitors, hydrophobic ligand-binding and transport proteins, extracellular matrix-interacting proteins, and transcription regulatory factors. The full length coding sequences were obtained for 11 clones representing a range of abundance levels. Expression of each is regionally localized and androgen regulated. The most abundant, ESC42, contains a cysteine-rich region similar to the signature binding domain of the trefoil family of motogenic wound repair proteins. The monkey and human proteins are nearly 90% identical. Immunohistochemical staining revealed that the protein is most abundant in the epithelium of the caput and is also present in the lumen and bound to sperm. The ESC42 gene, located on chromosome 20q11, contains two exons encoding two nearly identical predicted signal peptides and a third exon encoding the rest of the protein.

Amino Acid Sequence↗

PubMed2000

HE2beta and HE2gamma, new members of an epididymis-specific family of androgen-regulated proteins in the human.

HE2 is an epididymis-specific sperm-binding secretory protein. We isolated a family of HE2-related complementary DNAs from a human caput/corpus library. The transcripts code for identical 71-amino acid N-termini and different C-termini, and 5'- and 3'-untranslated regions. Compared with the original HE2, HE2beta and HE2gamma proteins have a 25-amino acid deletion near the C-terminus, and HE2gamma isoforms have a second deletion. These frame-shifting deletions result in C-termini differing in length, amino acid sequence, including number of cysteines, and isoelectric point. Identical sequences and deletion start and stop points indicate the HE2 isoforms are derived from alternative splicing of 8 or more exons of a single gene. Northern hybridization revealed that the 0.9-kb messenger RNA (mRNA) is most abundant in human caput; there is much less of it (20%) in corpus and little (<5%) in cauda. In castrated Macaca mulatta, HE2 mRNA decreased to 10% of sham-operated levels. Testosterone replacement maintained HE2 mRNA 3- to 5-fold higher than castrate levels, indicating its androgen dependence. Immunohistochemical staining revealed that the beta1 form is highly expressed in principal cells of the initial segment and caput. It is secreted into the lumen and binds to the sperm surface in the postacrosomal and neck regions. The beta2 form is expressed in principal cells primarily in efferent ducts.

3' Untranslated Regions↗

PubMed2000

Thyroid receptor activator molecule, TRAM-1, is an androgen receptor coactivator.

An androgen receptor (AR) interacting protein was isolated from a HeLa cell complementary DNA library by two-hybrid screening in yeast using the AR DNA and ligand binding domains [amino acids (aa) 481-919] as bait. AR binding of the protein in yeast was dependent on the presence of testosterone or dihydrotestosterone (DHT). The isolated protein is identical to thyroid receptor activator molecule TRAM-1 but lacking aa 1-458. TRAM-1 is a steroid receptor coactivator-3 (SRC-3) subtype. In affinity matrix assays, 35S-labeled TRAM-1 bound the GST-AR ligand binding domain (aa 624-919) and GST-AR N-terminal and DNA binding domains (aa 1-660), but not the GST-AR DNA binding domain (aa 544-634) alone. Coexpression of TRAM-1 increased DHT-dependent AR transactivation 5-fold and constitutive activity of AR (aa 1-660) N-terminal and DNA-binding domains increased 9-fold. Full-length TRAM-1 (aa 1-1424) and the partial (aa 459-1424) were AR and GR coactivators as was SRC-1. In human testis, immunostaining of SRC-3 colocalized with AR in nuclei of Sertoli cells and peritubular myoid cells, indicating it could function as an AR coactivator in these cells. SRC-3 was also present in nuclei of spermatogenic cells where AR was not expressed, suggesting it might also be a coactivator with other nuclear receptors that regulate spermatogenesis.

Acetyltransferases↗

PubMed2000

Protein inhibitor of activated STAT-1 (signal transducer and activator of transcription-1) is a nuclear receptor coregulator expressed in human testis.

An androgen receptor (AR) interacting protein was isolated from a HeLa cell cDNA library by two-hybrid screening in yeast using the AR DNA+ligand binding domains as bait. The protein has sequence identity with human protein inhibitor of activated signal transducer and activator of transcription (PIAS1) and human Gu RNA helicase II binding protein (GBP). Binding of PIAS1 to human AR DNA+ligand binding domains was androgen dependent in the yeast liquid beta-galactosidase assay. Activation of binding by dihydrotestosterone was greater than testosterone > estradiol > progesterone. PIAS1 binding to full-length human AR in a reversed yeast two hybrid system was also androgen dependent. [35S] PIAS1 bound a glutathione S-transferase-AR-DNA binding domain (amino acids 544-634) fusion protein in affinity matrix assays. In transient cotransfection assays using CV1 cells with full-length human AR and a mouse mammary tumor virus luciferase reporter vector, there was an androgen-dependent 3- to 5-fold greater increase in luciferase activity with PIAS1 over that obtained with an equal amount of control antisense cDNA or mutant PIAS1. Constitutive transcriptional activity of the AR N-terminal+DNA binding domain was increased 6-fold by PIAS1. PIAS1 also enhanced glucocorticoid receptor transactivation in response to dexamethasone but inhibited progesterone-induced progesterone receptor transactivation in the same assay system. mRNA for PIAS1 was highly expressed in testis of human, monkey, rat, and mouse. In rat testis the onset of PIAS1 mRNA expression coincided with the initiation of spermatogenesis between 25-30 days of age. Immunostaining of human and mouse testis with PIAS1-specific antiserum demonstrated coexpression of PIAS1 with AR in Sertoli cells and Leydig cells. In addition, PIAS1 was expressed in spermatogenic cells. The results suggest that PIAS1 functions in testis as a nuclear receptor transcriptional coregulator and may have a role in AR initiation and maintenance of spermatogenesis.

Aged↗

PubMed1999

Testis-brain RNA-binding protein (Translin) is primarily expressed in neurons of the mouse brain.

The subcellular location(s) of the DNA- and RNA-binding protein, Testis-Brain RNA-Binding Protein (TB-RBP)/Translin in mouse brain has been determined in paraffin sections by immunocytochemistry with an affinity purified antibody to mouse recombinant TB-RBP. Nuclear staining was frequently seen in neurons throughout the brain, but no TB-RBP/Translin was detected in many of the neurons in superficial layers of the cerebral cortex and in some cells of the cerebellum. Cytoplasmic staining extending into the dendrites was seen in large neurons such as pyramidal neurons in Layer 5 of the cortex and magnocellular neurons of the hypothalamus or the brainstem raphe.

Animals↗

PubMed1997

Arginine and NADPH diaphorase in the rat ventroposterior thalamic nucleus.

Simultaneous immunocytochemical staining for arginine (Arg) and histochemical staining for reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd, a marker for nitric oxide synthase) reveals that neuropil in the ventroposterior nucleus of the thalamus is enriched with both Arg-positive glial profiles and NADPHd-positive fibers. NADPHd-positive fibers are often apposed to Arg-positive astrocytes and oligodendrocytes. NADPHd-positive endothelial cells are often adjacent to Arg-positive astrocytes. The results suggest that Arg may be stored in supporting cells, whence it could be supplied to nearby nerve fibers or endothelial cells as substrate for nitric oxide synthase.

Animals↗

PubMed1997

Expression and distribution of androgen-binding protein/sex hormone-binding globulin in the female rodent reproductive system.

Androgen-binding protein (ABP)/sex hormone-binding globulin gene expression has been described in the rat testicular Sertoli cell and brain. The extracellular protein is thought to regulate the bioavailability of sex steroids, but may have a more complex function as a hormone or growth factor. Transgenic mice were developed with a 5.5-kilobase (kb) rat DNA fragment containing the ABP gene with all 8 exon sequences and 1.5 kb upstream of the transcription start site. Expression of the gene was observed in the testis and brain, but not in other examined tissues of the transgenic mice. In this paper we describe ABP gene expression in ovaries of transgenic mice that contain the rat gene; a lower level of ABP mRNA was also detected in the transgenic uterus. Northern blot analysis also detected ABP mRNA in rat ovary. The hybridizing species in the rat and transgenic mouse ovaries and uteri were the size of testicular ABP mRNA (1.7 kb). Except in the transgenic mouse brain, there was no detectable hybridizing RNA in the other transgenic tissues examined. The plasma, ovary, and uterus of the transgenic mice all contained elevated ABP (dihydrotestosterone [DHT]-binding) activities as compared to those of wild-type littermates; other wild-type and transgenic tissues were negative for DHT binding. Immunohistochemistry revealed increased immunoreactivity in the transgenic oviduct and uterus, but not the ovary. In the oviduct, the intense immunoreactivity was associated with the epithelium, whereas in the uterus it was primarily associated with the luminal epithelium and glands. Phenotypic abnormalities of the homozygous transgenic mice included reduced fecundity resulting in small litters. We conclude that ABP may function in the female reproductive system to increase the local concentrations of sex steroids or to sequester them in key target organs. Studies in the female will aid in elucidating the functions of ABP in male and female reproduction.

Amino Acid Sequence↗

PubMed1997

Overexpression of androgen-binding protein/sex hormone-binding globulin in male transgenic mice: tissue distribution and phenotypic disorders.

The rat androgen-binding protein/sex hormone-binding globulin (ABP/SHBG) gene in transgenic mice was previously shown to be specifically expressed in the testes. This study verifies a Sertoli cell location of ABP and translation of testicular ABP mRNA in the transgenic mice by dihydrotestosterone (DHT)-binding assays and immunohistochemistry. DHT-binding activities in the testis and epididymis of the hemizygous transgenic mice were elevated 20-fold as compared to activity in the wild-type tissues. DHT-binding activities were also elevated in blood plasma at least 25- to 50-fold in the transgenic mice; binding was undetectable in the plasma from control mice. Immunohistochemical analysis revealed that the transgenic testicular ABP was primarily in the cytoplasm of Sertoli cells and lumen of the seminiferous tubules. In some tubules, intense staining also was associated with spermatids. After transport to the epididymis, there were large amounts of immunoreactive ABP internalized in the epithelium of the initial segment and proximal caput. The increased levels of plasma and testicular ABP had no effect on levels of testosterone; there was a 30-fold range of plasma and testicular testosterone levels in the wild-type and transgenic mice. Increased ABP levels in the transgenic mice were associated with structural and functional abnormalities in the testis. Abnormal spermatogenesis resulted in extensive structural changes in the transgenic testis; the degree of the defect varied from near normality to the loss of most germ cells. In the affected mice, seminiferous tubules had smaller diameters and decreased numbers of germ cells, particularly in the spermatid stages of differentiation. Pyknotic nuclei and multinucleated cells were associated with the spermatids in the defective tubules, but not in the wild-type tubules. Consequently, mice with the spermatogenic disorder had reduced epididymal sperm numbers. The variable spermatogenic disorder was associated with variable male fertility. The homozygous transgenic male and female mice also had a serious motor dysfunction affecting their hind limbs. This study demonstrates how the transgenic mouse model can be used to study ABP's function, and the data support several hypotheses on its function in the testis and epididymis.

Androgen-Binding Protein↗

PubMed1996

Estradiol stimulates tyrosine phosphorylation of the insulin-like growth factor-1 receptor and insulin receptor substrate-1 in the uterus.

The signaling pathways associated with estrogen-induced proliferation of epithelial cells in the reproductive tract have not been defined. To identify receptor tyrosine kinases that are activated in vivo by 17 beta-estradiol (E2), uteri from ovariectomized mice were examined for enhanced tyrosine phosphorylation of various receptors and a receptor substrate following treatment with this hormone. Within 4 hr after hormone exposure, extracts showed increased phosphotyrosine (P-Tyr) immunoreactivity at several bands, including 170- and 180-kDa; these bands were still apparent at 24 hr after E2. Analysis of immunoprecipitates from uterine extracts revealed that E2 enhanced tyrosine phosphorylation of the insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor substrate-1 (IRS-1) by 6 hr. Comparison of supernatants from IRS-1 and control rabbit IgG immunoprecipitates indicated that the 170-kDa P-Tyr band in extracts was equivalent to IRS-1. The receptors for epidermal growth factor, platelet-derived growth factor, and basic fibroblast growth factor did not exhibit an E2-induced increase in P-Tyr content. The nonestrogenic steroid hormones examined did not stimulate the P-Tyr content of IGF-1R or IRS-1. Immunolocalization of P-Tyr and IRS-1 revealed strong reactivity in the epithelial layer of the uterus from E2-treated mice, suggesting that the majority of P-Tyr bands observed in immunoblots originate in the epithelium. Since hormonal activation of IRS-1 is epithelial, estrogen-specific, and initiated before maximal DNA synthesis occurs following treatment with hormone, this protein, as part of the IGF-1R pathway, may be important in mediating estrogen-stimulated proliferation in the uterus.

Animals↗

PubMed1996

Antibodies to glutamate, aspartate and glycyl-D-aspartate reversibly suppress stimulus-evoked, extracellularly recorded responses in slices of rat neocortex.

Polyclonal antibodies raised against glutamate, aspartate and the dipeptide, glycyl-D-aspartate were dissolved in artificial cerebrospinal fluid (aCSF) and administered at concentrations as low as 0.05% to slices of prefrontal cortex maintained in vitro. These antisera caused a reversible attenuation of evoked field potentials and/or single-unit activity recorded extracellularly following the delivery of shocks to the underlying white matter, or to cortical layer IV. To the best of our knowledge, this result provides the first demonstration using electrophysiological recording of the use of a transmitter-specific antibody as a blocker of synaptic transmission in living slices of the central nervous system (CNS). The results lend support to the suggestion that glutamate, aspartate, and a molecule related closely to glycyl-D-aspartate, are involved in synaptic transmission at major pathways within prefrontal cortex.

Animals↗

PubMed1996

Distribution of immunoreactive androgen-binding protein/sex hormone-binding globulin in tissues of the fetal rat.

Androgen-binding protein/sex hormone-binding globulin (ABP/SHBG) is an extracellular carrier protein that binds androgens and estrogens with high affinity. In the adult, ABP/SHBG is thought to function in the male reproductive system and the general circulation in both sexes to modulate the actions of sex steroids. The ABP/SHBG gene is also expressed in the embryonic rat liver, where SHBG is secreted into the fetal blood of male and female rats. The embryo also expresses an alternative SHBG with a unique N-terminal sequence. In this study, the distribution of immunoreactive SHBG in the 17-day-old male fetal rat was determined with six antisera. In general, all of the antisera reacted with the same structures. Specific tissue immunoreactivity was mostly cytoplasmic and/or extracellular. By far the most prominent immunoreactive structures were the mesoderm-derived tissues: connective tissue, striated and cardiac muscle, cartilage, and the liver hematopoietic system. In addition, all regions of the fetal brain contained immunoreactive neurons. In the developing male reproductive system, there was minor reactivity in the testicular cords, whereas the connective tissue in the differentiating Wolffian duct stained with all of the antisera. The Wolffian duct epithelium and epithelia in other developing organs contained small amounts of immunoreactive SHBG, except for the lung, which stained in the epithelial extracellular matrix. An antibody raised against a unique N-terminal peptide specific for the alternative SHBG protein revealed that it was also present in many tissues. These data suggest that SHBG is important for the differentiation of mesodermal tissues. SHBG may modulate the action of androgens in embryonic stroma, thereby regulating development of the epithelium in hormone-dependent tissues.

Amino Acid Sequence↗

PubMed1996

Immunohistochemical localization of nitric oxide synthase activity in upper respiratory epithelium.

Nitric oxide (NO) production in the respiratory epithelium of the upper airways has recently been described. To better delineate the role of epithelial NO, the authors of this study attempted to identify the cell type responsible for the production of NO in rat tracheal epithelium and human nasal epithelium. They localized the activity of NO through immunohistochemical analysis with an antibody to L-citrulline, a marker for activity of the L-arginine-dependent nitric oxide synthase (NOS) pathway. Using anti-inducible NOS (iNOS) and anti-constitutive NOS (cNOS) antibodies, they also attempted to identify the specific NO isotypes that were present. The tracheal and nasal epithelium demonstrated strong immunoreactivity to citrulline in ciliated cells. The ciliated cells of the nasal turbinates demonstrated strong iNOS positivity, but no significant cNOS immunoreactivity. The study findings that iNOS activity is present in ciliated epithelial cells of rat and human upper respiratory epithelium suggest that NO may play a role in epithelial homeostasis and could potentially play a role in the pathogenesis of mucociliary dysfunction.

Animals↗

PubMed1996

Local production of corticotropin releasing hormone is increased in experimental intestinal inflammation in rats.

BACKGROUND/AIMS: Corticotropin releasing hormone (CRH) suppresses immunological functions via stimulation of the pituitary-adrenal axis, but is also found in peripheral tissues. Peripheral proinflammatory activity of CRH is suggested by increased tissue concentrations in arthritis and in vitro immunostimulatory effects. This study evaluated intestinal CRH concentrations, immunolocalisation, and synthesis in chronic enterocolitis and investigated in vitro responsiveness of lamina propria mononuclear cells to CRH. METHODS: Chronic granulomatous enterocolitis was induced by intramural injection of peptidoglycan-polysaccharide polymers in the ileocaecal region of Lewis rats. CRH protein was measured in caecal specimens by immunohistochemistry and radioimmunoassay and caecal CRH mRNA expression was analysed by reverse transcriptase polymerase chain reaction. RESULTS: In the chronically inflamed caecum abundant immunoreactive CRH was found in inflammatory cells, mesenchymal cells, as well as in myenteric plexi. In contrast, only a few CRH containing cells were detected in normal and HSA injected control caecums. Moreover, caecal CRH protein levels were increased during chronic enterocolitis. Local CRH synthesis as indicated by mRNA expression was considerably increased in chronic enterocolitis whereas it was undetectable or low in uninflamed caecum. In addition, CRH stimulated in vitro proliferation of lamina propria mononuclear cells and inhibited mitogen induced proliferation. CONCLUSION: Increased CRH protein and mRNA expression in chronic enterocolitis and responsiveness of intestinal mononuclear cells to CRH indicate an immunomodulatory role for locally produced CRH in intestinal inflammation.

Animals↗