Cholecystokinin inhibits gastrin secretion independently of paracrine somatostatin secretion in the pig

Background: Cholecystokinin inhibits the secretion of gastrin from antral G cells, an effect that is speculated to be mediated by D cells secreting somatostatin. The aim of the study was to test directly whether cholecystokinin inhibition of antral gastrin secretion is mediated by somatostatin. Methods: The effects of CCK on gastrin and somatostatin secretion were studied in isolated vascularly perfused preparations of pig antrum before and after immunoneutralization brought about by infusion of large amounts of a high affinity monoclonal antibody against somatostatin. Results: CCK infusion at 10 ^?9 M and 10 ^?8 M decreased gastrin output to 70.5%?±?7.6% (n?=?8) and 76.3%?±?3.6% (n?=?7) of basal output, respectively. CCK at 10 ^?10 M had no effect (n?=?6). Somatostatin secretion was dose‐dependently increased by CCK infusion and increased to 268?±?38.2% (n?=?7) of basal secretion during infusion of CCK at 10 ^?8 M. Immunoneutralization of somatostatin caused a doubling of the basal secretion of gastrin, but did not affect the CCK‐induced decrease in gastrin secretion. Conclusion: CCK inhibits gastrin secretion independently of paracrine somatostatin secretion.     

Mesenchymal stem cells attenuate hypoxic pulmonary vasoconstriction by a paracrine mechanism

BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) may be an adaptive mechanism to correct ventilation-perfusion mismatch in the face of hypoxia. In chronic hypoxia, prolonged vasoconstriction may result in pulmonary hypertension and cor pulmonale. It has been shown that during chronic hypoxia, mesenchymal stem cells (MSCs) may contribute to pulmonary vascular remodeling, anti-inflammation, and vascular stability. Also, MSCs have been shown to release growth factors when stressed by hypoxia. We hypothesized that MSCs reduce HPV by a paracrine mechanism. To test this, MSCs were stressed by hypoxia in tissue culture and the cell-free media was then used to treat the pulmonary arteries subjected to HPV. METHODS: Adult male (250-350 g) Sprague Dawley rat pulmonary arteries (n = 10/group) were isolated and suspended in physiological organ baths. Human MSCs were stressed with 60-min hypoxia and conditioned media was collected. Pulmonary artery rings were treated with vehicle or MSC-conditioned (cell-free) media prior to hypoxia. Force displacement was continuously recorded. Data (mean +/- SEM) were analyzed with two-way analysis of variance with post-hoc Bonferroni test. RESULTS: Pulmonary arteries exposed to MSC-conditioned media experienced an augmented vasodilatory phase as compared to vehicle. Maximum vasodilation was 53.58 +/- 6.42% versus 39.76 +/- 4.05% for vehicle (P < 0.001). In addition, delayed, phase II vasoconstriction was significantly attenuated as compared to vehicle. Maximum phase II vasoconstriction was 28.51 +/- 12.42 versus 86.29 +/- 15.99% for vehicle (P < 0.001). CONCLUSIONS: We conclude that acute hypoxia induces HPV and that MSC-conditioned media acutely attenuates this effect. Thus, in addition to a direct contribution to vessel remodeling in chronic hypoxia, MSCs may acutely protect and attenuate hypoxic pulmonary vasoreactivity through a paracrine mechanism.     

Paracrinicity: the story of 30 years of cellular pituitary crosstalk

Living organisms represent, in essence, dynamic interactions of high complexity between membrane-separated compartments that cannot exist on their own, but reach behaviour in co-ordination. In multicellular organisms, there must be communication and co-ordination between individual cells and cell groups to achieve appropriate behaviour of the system. Depending on the mode of signal transportation and the target, intercellular communication is neuronal, hormonal, paracrine or juxtacrine. Cell signalling can also be self-targeting or autocrine. Although the notion of paracrine and autocrine signalling was already suggested more than 100 years ago, it is only during the last 30 years that these mechanisms have been characterised. In the anterior pituitary, paracrine communication and autocrine loops that operate during fetal and postnatal development in mammals and lower vertebrates have been shown in all hormonal cell types and in folliculo-stellate cells. More than 100 compounds have been identified that have, or may have, paracrine or autocrine actions. They include the neurotransmitters acetylcholine and gamma-aminobutyric acid, peptides such as vasoactive intestinal peptide, galanin, endothelins, calcitonin, neuromedin B and melanocortins, growth factors of the epidermal growth factor, fibroblast growth factor, nerve growth factor and transforming growth factor-beta families, cytokines, tissue factors such as annexin-1 and follistatin, hormones, nitric oxide, purines, retinoids and fatty acid derivatives. In addition, connective tissue cells, endothelial cells and vascular pericytes may influence paracrinicity by delivering growth factors, cytokines, heparan sulphate proteoglycans and proteases. Basement membranes may influence paracrine signalling through the binding of signalling molecules to heparan sulphate proteoglycans. Paracrine/autocrine actions are highly context-dependent. They are turned on/off when hormonal outputs need to be adapted to changing demands of the organism, such as during reproduction, stress, inflammation, starvation and circadian rhythms. Specificity and selectivity in autocrine/paracrine interactions may rely on microanatomical specialisations, functional compartmentalisation in receptor-ligand distribution and the non-equilibrium dynamics of the receptor-ligand interactions in the loops.     

Recombinant human follicle-stimulating hormone as a pretreatment for idiopathic oligoasthenoteratozoospermic patients undergoing intracytoplasmic sperm injection

OBJECTIVE: To evaluate the efficacy of recombinant human FSH pretreatment in improving fertilization and pregnancy rates in oligozoospermic patients who are undergoing ICSI. DESIGN: Prospective, controlled, clinical study. SETTING: A research institute's reproductive unit. PATIENT(S): Thirty-three subjects with idiopathic oligoasthenoteratozoospermia who failed to conceive after previous ICSI attempts. INTERVENTION(S): Treatment with recombinant human FSH 150 IU for 3 months (23 patients) or no treatment (10 patients); clinical, hormonal, and seminal evaluation before and after treatment. MAIN OUTCOME MEASURE(S): Testicular volume, sperm parameters, FSH, LH, T, E(2), and inhibin B plasma levels, E/T ratio, and fertilization and pregnancy rates. RESULT(S): Treatment with 150 IU of FSH induced a significant increase in testicular volume and sperm parameters. The mean fertilization rate (FR) after ICSI cycles was higher, although not significantly, in treated patients when compared with controls (62.3 +/- 22.4 vs. 47.2 +/- 20.4). A strong negative correlation was observed between FR and serum FSH, inhibin B and E/T ratio in controls, whereas in treated patients, FR correlated with posttreatment inhibin B levels. The pregnancy rate in the entire treated group was 30.4%. No pregnancies were recorded in the control group. CONCLUSION(S): Recombinant human FSH may be a valuable pretreatment for oligozoospermic patients undergoing ICSI and may influence testicular paracrine activity.     

卵泡发育早期细胞因子对卵母细胞发育的调控

在卵泡内,卵母细胞及其周围颗粒细胞间的旁分泌作用对卵母细胞的发育和功能有重要作用.研究证实了源于颗粒细胞的酪氨酸激酶受体配体在卵母细胞生长过程中起重要作用.酪氨酸激酶受体配体和源于卵母细胞的生长分化因子-9以及骨生成蛋白-15间的相互作用表明卵母细胞和颗粒细胞在分子水平上存在复杂的作用.卵泡刺激素调控这些旁分泌作用并调节卵泡正常发育.促进卵母细胞发育的分子机制可应用于人的体外生长系统并改善生育.     

The phakomatoses as paracrine growth disorders (paracrinopathies)

A microcomputer database management system retrieved all 170 probands with phakomatoses evaluated through the genetic clinics at the University of South Florida between January 2, 1982 and December 31, 1987. Neurofibromatosis (NF) was the diagnosis of 118 of them; 42 had other phakomatoses and 10 had transitional phenotypes difficult to classify. The analysis of the hamartomas of all probands indicated disorganized differentiation and overgrowth of cell species characteristic for the involved tissue and location. Abundance of extracellular fibrillary components was also evident in most hamartomas. Adequate blood supply was a conditio sine qua non. This was seen in monogenic, sporadic, transitional and combined phakomatoses alike and implied a common pathogenesis. The paracrine growth factors and their regulation emerged as the most plausible common denominator for the pathogenesis. A unitary pathogenetic hypothesis is proposed that the phakomatoses represent paracrine growth regulation disorders (paracrinopathies). Conditions such as fibromatoses, lipomatoses, lipodystrophies, hemihyper/hypotrophies, including Russell-Silver and Beckwith-Wiedemann syndromes may be proven to be paracrinopathies as well.     

Chorion releases a factor that inhibits oxytocin-stimulated myometrial contractility in the pregnant guinea pig

It was postulated that chorion releases a substance necessary for the maintenance of uterine quiescence during pregnancy. A decrease in the release of this substance at the end of the pregnancy would be necessary for normal myometrial activation. This hypothesis was tested by demonstrating the ability of chorion to inhibit oxytocin-stimulated myometrial contractility in vitro. Tissues were obtained from timed pregnant Duncan-Hartley guinea pigs either at pre-term or near-term gestation. Myometrial strips were placed in organ baths for isometric tension measurement and contractions stimulated by oxytocin (10(-8) mol/l). Fetal membranes or conditioned medium from chorion were added directly to the organ bath. Near-term chorion and chorion conditioned-medium decreased oxytocin-stimulated contractile activity to 39% and 49% respectively. Neither pre-term nor near-term amnion reduced oxytocin-stimulated myometrial contractile activity. Relaxation induced by pre-term chorion was greater than near-term chorion (23% and 41% of the oxytocin-induced basal level respectively; P < 0.05). Further, chorion-induced relaxation was independent of the gestational age of the myometrium. Human chorion from a term, not-in-labour woman also inhibited oxytocin-stimulated guinea pig myometrial contractility. It was concluded that the chorion releases a substance or substances that reduce oxytocin-stimulated myometrial contractility and may be involved in the maintenance of uterine quiescence during pregnancy.