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Results for “Paracrine Communication”

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At least 55 records · Page 3Linked to original sources

PubMed2003

GCNF-dependent repression of BMP-15 and GDF-9 mediates gamete regulation of female fertility.

To determine the function of germ cell nuclear factor (GCNF) in female reproduction, we generated an oocyte-specific GCNF knockout mouse model (GCNF(fl/fl)Zp3Cre(+)). These mice displayed hypofertility due to prolonged diestrus phase of the estrous cycle and aberrant steroidogenesis. These reproductive defects were secondary to a primary defect in the oocytes, in which expression of the paracrine transforming growth factor-beta signaling molecules, bone morphogenetic protein 15 (BMP-15) and growth differentiation factor 9 (GDF-9), were up-regulated in GCNF(fl/fl)Zp3Cre(+) females at diestrus. This was a direct effect of GCNF, as molecular studies showed that GCNF bound to DR0 elements within the BMP-15 and GDF-9 gene promoters and repressed their reporter activities. Consistent with these findings, abnormal double-oocyte follicles, indicative of aberrant BMP-15/GDF-9 expression, were observed in GCNF(fl/fl)Zp3Cre(+) females. The Cre/loxP knockout of GCNF in the oocyte has uncovered a new regulatory pathway in ovarian function. Our results show that GCNF directly regulates paracrine communication between the oocyte and somatic cells by regulating the expression of BMP-15 and GDF-9, to affect female fertility.

Animals↗

PubMed2005

Effect of oestradiol on mouse uterine epithelial cell tumour necrosis factor-alpha release is mediated through uterine stromal cells.

Oestradiol-17beta (Oe(2)) stimulates uterine epithelial cell proliferation and is critical for normal uterine differentiation and secretory function. Oe(2) can act directly on the epithelium via the epithelial oestrogen receptor (OR) or indirectly via the OR-positive underlying stroma. A primary role for epithelial-stromal interactions has been established for mediating steroid hormone action in the uterus. This study was undertaken to determine the mode of Oe(2) action in regulating epithelial cell cytokine release in the uterus. Mouse uterine epithelial and stromal cells were isolated and cultured separately. Transepithelial resistance (TER) was monitored with an EVOM voltohmmeter to determine monolayer polarity and integrity. Epithelial cells grown alone or in coculture with stromal cells were treated with Oe(2). Supernatants collected were assayed for transforming growth factor-beta (TGF-beta) and tumour necrosis factor-alpha (TNF-alpha) by bioassay and enzyme-linked immunosorbent assay, respectively. While Oe(2) treatment of epithelial cells led to a significant decrease in TER, the amount of TNF-alpha released was not altered. However, when epithelial cells were cocultured with stromal cells and treated with Oe(2), apical TNF-alpha release was significantly decreased, compared to cells not treated with hormone. As determined by oestrogen receptor antagonist studies, Oe(2) primed epithelial cells for the action of the stromal paracrine factor(s). In contrast, TGF-beta release by epithelial cells was not affected by Oe(2) when grown alone or in the presence of stromal cells. These studies indicate that Oe(2) has both direct and indirect effects on the uterine epithelium. While epithelial monolayer integrity is directly influenced by Oe(2), TNF-alpha release in response to Oe(2) is dependent on the presence of stromal cells, indicating that paracrine communication is necessary for steroid regulation of some but not all cytokines.

Animals↗

PubMed1993

Cellular localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in rat brain.

The distribution of interleukin 6 (IL-6) mRNA and IL-6 receptor (IL-6R) mRNA in the brain of adult male rats was studied at the light microscope level by in situ hybridization histochemistry using 35S-labelled oligonucleotides. The transcripts of both genes were localized in the pyramidal neurons and in the granular neurons of the hippocampus, in neurons of the habenular nucleus as well as in the dorsomedial and ventromedial hypothalamus, in the piriform cortex, in scattered neurons of the cortex and in granular cells of the cerebellum. The medial preoptic nucleus and the anterior tip of the lateral ventricle contained mRNA encoding IL-6 and its receptor. Moreover, white matter areas, such as the internal capsule, which consist of only fibres and glial cells, were found to have autoradiographic signals above background. The mRNAs for IL-6 and IL-6R in hippocampus and cerebellum are not different, as shown by Northern blot analyses of RNA isolated from these tissues. We postulate that the cytokine IL-6 is expressed constitutively in discrete regions of the CNS and that it is involved in the mechanisms coordinating metabolic, behavioural and neuroendocrine changes not only during illness but also under normal physiological conditions. Our results suggest that IL-6 mRNA and IL-6R mRNA are colocalized, thus supporting a role of the cytokine in autocrine and paracrine communication.

Animals↗

PubMed2002

Neonatal ovine adrenal cortical and medullary Cell H+ responses to ACTH and prostaglandin E(2).

The microphysiometric technique was used to evaluate 1- and 3-day-old lamb adrenal gland H+ production in response to ACTH or PGE(2). ACTH stimulated cortical, but not medullary H+ production; maximal H+ by combined cortical and medullary cells was greater than by cortical cells alone (p < 0.05). In contrast, the magnitude of the H+ response to PGE(2) was greater with medullary than with cortical cells alone or with cortical and medullary cells combined (p < 0.05). The H+ response to ACTH was greater in 3-day-old compared to 1-day-old lambs while the potency of PGE(2) was not different at the ages studied. We conclude that in neonatal sheep: (1) ACTH and PGE(2) are potentially important in adrenal regulation, and (2) paracrine communication appears to be functioning as has been shown for adults.

Adrenal Cortex↗

PubMed2000

Expression of neuronal nitric oxide synthase in several cell types of the rat gastric epithelium.

The aim of this study was to identify which cell types of the rat gastric epithelium express neuronal nitric oxide synthase (nNOS) because the results of the previous studies have been very divergent regarding this point. By the combination of immunohistochemical (IHC) and in situ hybridization (ISH) techniques, we detected expression of nNOS in chief and mucosecretory cells of the gastric epithelium. Moreover, some gastric endocrine cells were immunoreactive for nNOS, although they could not be distinguished in sections treated with ISH techniques. The strongest signal for all antibodies in IHC techniques was obtained when microwave (MW) heating was performed before the IHC procedure. Our results indicate that in the gastric epithelium a variety of cell types are able to produce NO. The NO produced by the different cell types (chief, mucous, and endocrine) may form a complex network of paracrine communication with an important role in gastric physiology.

Animals↗

PubMed1999

Neonatal estrogen stimulates proliferation of periductal fibroblasts and alters the extracellular matrix composition in the rat prostate.

The purpose of this study was to examine whether changes in extracellular matrix (ECM) molecules are associated with the growth inhibition and differentiation defects of the prostate gland following neonatal exposure to estradiol. Using immunocytochemistry (ICC), laminin and collagen IV were localized to the basement membrane (BM) as well to the basal lamina of the periductal smooth muscle of the control developing prostates. In contrast, fibronectin and collagen III were localized throughout the stromal ECM. Exposure to neonatal estrogen altered the staining profile for specific ECM molecules. In the estrogenized rats, a thick layer of cells negative for laminin and collagen IV was observed adjacent to the BM. Electron microscopy and ICC for alpha-actin, fibronectin, and vimentin identified this multicellular layer of periductal cells as differentiated fibroblasts. Peripheral to these fibroblasts, actin-positive smooth muscle formed a second layer of periductal stromal cells. PCNA labeling showed that estrogen exposure increased the fibroblast proliferation. Because many periductal fibroblasts were positive for estrogen receptor alpha (ER alpha) in estrogenized rats, a direct effect of estradiol on their proliferation is suggested. Gelatinolytic gels revealed that estrogen exposure did not alter the activity of matrix metalloproteinases associated with tissue remodeling during prostate morphogenesis. However, the periductal fibroblast layer in estrogenized prostates was devoid of urokinase- and tissue-plasminogen activator, which may potentially alter the localized proteolysis involved in matrix remodeling. It is proposed that proliferation of a multicellular layer of periductal fibroblasts in estrogenized prostates results in a physical barrier that constrains branching morphogenesis and blocks paracrine communications between smooth muscle and epithelial cells which normally regulate differentiation.

Animals↗

PubMed2004

Impaired Leydig cell function in infertile men: a study of 357 idiopathic infertile men and 318 proven fertile controls.

To investigate whether an impaired Leydig cell function is present in severely oligospermic men, serum testosterone (T), LH, estradiol (E(2)), and SHBG levels in 357 idiopathic infertile men were compared with levels in 318 proven fertile men. In addition, the T/LH ratio, E(2)/T ratio, and calculated free T index (cFT) were compared between the two groups.A shift toward lower serum T levels, cFT, and T/LH ratio and higher serum LH, E(2), and E(2)/T levels was observed in the group of infertile men. On average, the infertile men had 18, 26, and 34% lower serum T, cFT, and T/LH levels, respectively, and 19, 18, and 33% higher serum LH, E(2), and E(2)/T levels, respectively, than the fertile men. Twelve percent of the infertile men had a serum T level that fell below the 2.5 percentile of the fertile levels, and 15% of the infertile men had a LH level that was above the 97.5 percentile of the fertile levels.Thus, the group of infertile men showed significant signs of impaired Leydig cell function in parallel to their impaired spermatogenesis. The association of decreased spermatogenesis and impaired Leydig cell function might reflect a disturbed paracrine communication between the seminiferous epithelium and the Leydig cells, triggered by distorted function of the seminiferous epithelium. On the other hand, the parallel impairment of spermatogenesis and Leydig cells may reflect a congenital dysfunction of both compartments caused by a testicular dysgenesis during fetal/infant development.

Adult↗

PubMed2003

Reduced expression of P2Y1 receptors in connexin43-null mice alters calcium signaling and migration of neural progenitor cells.

Glial calcium signals play important roles during CNS development. Calcium transients induced by ATP, acting on purinergic receptors, stimulate DNA synthesis, increase astrocytic and neural stem cell proliferation, and are prominent during the differentiation of radial glia. We have shown previously that expression of P2Y receptors in astrocytes is altered when connexin43 (Cx43) is downregulated. To evaluate the consequences of Cx43 deletion on calcium signaling during neural progenitor development, studies were performed on neurospheres derived from embryonic striatum. After adhesion, cells migrating from wild-type (WT) and Cx43-null neurospheres displayed spontaneous calcium oscillations. Such activity was blunted by apyrase, 2'-deoxy-N6-methyladenosine 3',5'-bisphosphate (MRS-2179), and suramin, suggesting that ATP released by neural cells acts on purinergic receptors to induce calcium oscillations. The amplitudes of Ca2+ transients induced by P2Y but not P2X receptor agonists were larger in WT than in Cx43-null progenitors, suggesting that these two cell populations express different P2 receptors. Suramin, a nonselective P2 receptor antagonist, and MRS-2179, a P2Y1 receptor-selective antagonist, reduced the proliferation rate and the migration of WT progenitor cells to levels similar to those of Cx43-null cells. Conversely, exogenous expression of P2Y1 receptors in Cx43-null cells restored their migration pattern to levels seen in WT progenitors. However, treatment with P2 receptor antagonists did not alter the ratio of nestin to GFAP expression in WT neural progenitors. These data show that altered autocrine-paracrine communication attributable to reduced levels of P2Y1 receptors in neural progenitor cells lacking Cx43 affects proliferation and migration but not cell differentiation during early CNS development.

Adenosine Triphosphate↗

PubMed1992

Brain and behaviour: morphological and functional aspects of the hypothalamus in the rat.

In a short historical overview some developments in the behavioural research of the hypothalamus of the rat are introduced. Especially the ventromedial and the lateral hypothalamus have received much attention in the past. Numerous different behavioural effects have been described as the result of some kind of activation or inactivation of parts of the hypothalamus in the rat. Questions concerning the topographical distribution and the specificity of the effects observed, are addressed in the later parts. These behavioural observations were very important for the comparison with our anatomical observations concerning the hypothalamus, including the topographical organization of some afferent and efferent relationships. Non-synaptic or paracrine communication may play an important role in the hypothalamic effects on the organization of behaviour.

Animals↗

PubMed1990

Advances in pathogenesis of goitre.

Growth regulation of the thyroid has been reinvestigated using an ex vivo system of isolated porcine thyroid follicles. Not only the direct effect of TSH, EGF, IGF I as well as iodine on growth of these follicles has been investigated but also the paracrine communication of these follicles with endothelial cells and fibroblasts. The results of recently published investigations with this culture system are summarized in this article. We could demonstrate that IGF I and EGF have a dose related effect on thyroid cell proliferation, whereas TSH has no effect on thyroid cell growth, if the iodine content of follicles is kept normal. Saturation of thyroid follicles with increasing amounts of iodine (1-40 microM K1) inhibit dose dependent EGF, IGF I or fetal calf serum induced thyroid cell proliferation. Inhibition of iodide organification with PTU or MMI abolish the growth inhibitory effect of iodide indicating that an organified iodinated product is responsible for the growth inhibitory effect of iodide on thyroid cell proliferation. Thyroid follicles secrete a FGF like substance which stimulates the growth of fibroblasts as well as endothelial cells. The secretion of FGF into the culture medium is decreased during TSH stimulation and enhanced during stimulation with EGF. The pretreatment of follicles with iodide abolishes the growth promoting effect of conditioned medium from thyroid follicles on fibroblasts and endothelial cells. We conclude that local growth factors like IGF I and EGF are responsible for thyroid cell proliferation whereas TSH stimulates specific function and hypertrophy of thyroid cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Local control mechanisms in the testis.

The gonads are unique organs in that they harbor the cells of the germline and consequently provide the local environment necessary for the normal development and differentiation of gametes. Since the local requirements for germ differentiation differ considerably from those of somatic cells the structural and physiological organization of the gonad is complex and compartmentalized. An elaborate network of local paracrine interactions between the somatic and gametogenic elements appears to be essential for normal germ cell development in mammals. This is especially true for the testis where meiosis is continuous throughout adulthood and where the spermatogenic cycle of the seminiferous epithelium is strictly controlled in time and space. The present paper reviews briefly the rapidly expanding field of testicular paracrinology. Special emphasis is given to the role of intra- and intercompartmental paracrine communication in the development of the male gamete.

Animals↗

PubMedDate not supplied

Appearance of alpha-smooth muscle actin in peritubular cells of monkey testes is induced by androgens, modulated by follicle-stimulating hormone, and maintained after hormonal withdrawal.

This study analyzed the hormonal requirements necessary for the development of primate testicular peritubular cells. Alpha-smooth muscle actin, as a specific differentiation marker for peritubular cells, was immunohistochemically detected in the testes of immature rhesus and adult rhesus and cynomolgus monkeys. Positive staining was localized in the wall of blood vessels and in peritubular myoid cells of adult animals. In the testis of vehicle-treated immature monkeys no positive staining could be detected in peritubular cells. Following follicle-stimulating hormone (FSH) or testosterone treatment, immunostaining for alpha-smooth muscle actin appeared in peritubular cells of immature animals. In comparison to FSH, testosterone was more effective in inducing the differentiation of peritubular cells. The most intense label for alpha-smooth muscle actin was, however, obtained after combined treatment with FSH and testosterone. A computer-assisted image analysis system was used to evaluate semiquantitative data for the alpha-smooth muscle actin positive area; this confirmed a significantly higher expression of alpha-smooth muscle actin in peritubular cells of immature monkeys after treatment with testosterone plus FSH in comparison to controls. These data present evidence that the differentiation of primate peritubular cells during pubertal sexual development is a hormone-dependent process, which may be predominantly regulated by androgens. FSH exerted additive effects on the androgen-induced differentiation of peritubular cells, suggesting that paracrine communication between peritubular cells and Sertoli cells existed. Maintenance of peritubular cell differentiation after withdrawal of hormonal stimuli in adult monkeys may be a possible explanation for different hormonal requirements during reinitiation of spermatogenesis after testicular involution.

Actins↗

PubMed1997

Aromatase expression and its localization in human breast cancer.

Aromatization or in situ estrogen production by aromatase has been considered to play an important role in the development of human breast carcinoma. In the human breast, aromatase overexpression is observed in the stromal or interstitial cells of the carcinoma, especially at the sites of frank invasion and/or adipose tissue. Transplantation experiments in the nude mouse employing MCF-7 and/or SF-TY human fibroblast cell lines revealed that aromatase activity and expression were much higher in the tumour with MCF-7 and SF-TY than that with MCF-7 alone. Aromatase overexpression in human breast carcinoma tissue is considered to occur as a result of carcinoma-stromal cell interactions, i.e. paracrine communication between stromal and carcinoma cells. Aromatase overexpression is correlated with the malignant phenotype in the human breast, but not with stage, age, clinical stages, clinical course, or proliferative activity of breast carcinoma. Aromatase overexpression may be correlated with development, rather than the biological behaviour of breast malignancy. Aromatase overexpression is not necessarily correlated with expression of 17beta-hydroxysteroid dehydrogenase type 1, which converts estrone to estradiol and estrogen receptor. Different mechanisms may be involved in the regulation of expression of these two important estrogen-metabolizing enzymes and estrogen receptor in human breast cancer. Aromatase overexpression in intratumoral stromal cells was much more frequently detected in male breast cancer than in female counterparts, which confers a growth advantage on cancer cells in a male hormonal environment with low serum estrogen levels.

Animals↗

PubMed1994

Endocrine-paracrine interaction in communication between the immune and endocrine systems. Activation of the hypothalamic-pituitary-adrenal axis in inflammation.

There are bidirectional communications between the immune and endocrine systems. Cytokines produced in inflammatory foci cause changes in the endocrine system, including activation of the hypothalamic-pituitary-adrenal (HPA) axis. Hormones produced in the endocrine system, especially glucocorticoids, affect the immune system to modulate its function. This is an important endocrine system for the defence mechanism. In addition, bacterial lipopolysaccharide produces cytokines in the brain and endocrine organs which are considered to act through the paracrine mechanism to regulate the HPA axis. Endocrine-paracrine interaction is important for the defence mechanism of the organism.

Animals↗

PubMed2000

Sharing calcium opens new avenues of signalling.

A consequence of intracellular calcium signalling is that calcium released into the cytosol is extruded from the cell. New research shows that when the interstitial space is constricted, calcium extruded from one cell may increase levels of calcium in the surrounding medium sufficiently to activate calcium-sensing receptors on the surfaces of adjacent cells. Thus, the calcium that serves as an intracellular signal can also serve as an extracellular signal to recruit neighbouring cells.

Calcium↗

PubMed2003

The autocrine/paracrine regulation of thyrotropin secretion.

Peptides originally described in other tissues have been located in the anterior pituitary gland. Detection of their encoding mRNAs and specific receptors, together with demonstration of peptide local action led to the postulation of the existence of a paracrine/autocrine regulation of pituitary function. Direct evidence for the role of endogenous peptides has come from studies aiming to block their action through immunoneutralization or pharmacologic blockade. Here we review evidence of pituitary produced peptides as potential candidates as local regulators of thyrotropin secretion. Few studies have approached the subject and most data are not conclusive. Until now, the most consistent data relate to neuromedin B, a bombesin-like peptide. The combined observation of high peptide concentration in rat thyrotrophs, the ability of the exogenous peptide to inhibit thyrotropin (TSH) release in physiologic doses plus the effect of the specific neuromedin B antiserum to increase basal TSH release from isolated pituitaries suggest that neuromedin B acts as a constitutive autocrine TSH-release inhibitor. Neuromedin B is upregulated by thyroid hormones and downregulated by thyrotropin-releasing hormone (TRH) that is consistent with proposed role of local factors, namely to partially mediate or modulate the effects of hormones on pituitary function. However, future studies will certainly confirm other candidates as local regulators of TSH secretion, as well as their relevance at physiologic and pathologic conditions.

Animals↗

PubMedDate not supplied

Vasopressin : a potent autocrine/paracrine regulator of mammal adrenal functions.

The control of adrenal functions by locally secreted neuropeptides or neurotransmitters is of great physiological importance. Vasopressin (VP) is one of these autocrine/paracrine regulators. We demonstrated by RT-PCR and perifusion experiments that rat and human adrenal medulla expressed and released vasopressin under basal conditions and under stimulation by acetylcholine. Intra-adrenal concentrations of VP may be sufficient to activate adrenal VP receptors. In the cortex, only the V1a receptor subtype has been detected. It triggered both steroid secretion and cortical growth. In the medulla, both V1a and V1b receptor subtypes were expressed. V1b receptors were mainly present on chromaffin cells and stimulated catecholamine secretion. The role of the V1a receptor remains unclear. Pathophysiological studies also revealed that human pheochromocytoma did not overexpress vasopressin receptors but might oversecrete vasopressin causing high plasma VP concentrations and elevated blood pressure.

Adrenal Glands↗

PubMed2006

Enigmatic GABAergic networks in adult neurogenic zones.

The discovery and description of complex GABAergic networks in adult neurogenic zones suggest the intriguing possibility of information transfer from neuronal activity to immature cells. New questions also emerge regarding the mode of GABAergic signaling and the temporal pattern of receptor activation. Non-synaptic (paracrine) signaling communicates information on population size to control the proliferation and migration of progenitor cells in the subventricular zone. How this signaling relates to olfactory bulb network activity, however, remains largely unknown. This review argues that paracrine signaling precedes and then co-exists with synaptic GABAergic signaling, which provides the timing and instruction for cells to properly differentiate and synaptically integrate into an existing network. The evidence examined in this review indicates that the commonly cited mechanism of GABA's action (i.e., depolarization leading to voltage-gated calcium channel activation and calcium entry) needs to be re-examined in the context of the unique cellular properties and organization of the adult neurogenic regions.

Animals↗