Biomedical subjects

N Ling

Publications and source records attributed to N Ling.

At least 19 recordsLinked to original sources

PubMed1992

Decrease in beta-subunit phosphotyrosine correlates with internalization and activation of the endosomal insulin receptor kinase.

In a previous study, we showed that the rat hepatic insulin receptor (IR) kinase of endosomes (ENs) was transiently activated to levels exceeding those of plasma membrane (PM) receptors following insulin injection. Phosphatase treatment of EN receptors abolished IR kinase activation implicating beta-subunit autophosphorylation as a mediator of the activation process (Khan, M. N., Baquiran, G., Brule, C., Burgess, J., Foster, B., Bergeron, J. J. M., and Posner, B. I. (1989) J. Biol. Chem. 264, 12931-12940). In the present study, the phosphotyrosine (PY) content of the IR beta-subunit in PM and ENs was estimated by two different methods. In one method, direct in vivo labeling with 32Pi followed by receptor immunoprecipitation was carried out. In the second method, immunoblotting with antibodies against the submembrane domain of the IR beta-subunit, encompassing residue 960 (alpha 960), and with antibodies against PY (alpha PY) was used to determine the content of PY/beta-subunit in PM and ENs following injection of insulin. By both methods, it was found that the PY content of PM IR was significantly greater than that of IR in ENs. With doses of 1.5 micrograms of insulin/100 g body weight (50% receptor occupancy) or 15 micrograms/100 g body weight (receptor saturation), the PY/beta-subunit of PM IR attained a level 2.0 to 2.5-fold of that observed for the IR of ENs. Surprisingly, the IR of ENs incorporated 3 to 5 times more PY/beta-subunit than those of PM consequent to autophosphorylation. Exogenous IR kinase activity (poly(Glu:Tyr)) in PM changed only slightly with insulin dose. In contrast, EN receptors exhibited a dose-dependent increase in kinase activity coincident with the decrease in PY/beta-subunit levels. A comparison of the proportion of receptor and kinase activity immunoprecipitated by alpha PY both before and after autophosphorylation indicated that ENs but not PM contained a small population of lightly phosphorylated but highly activated receptors. Since Thr12-Lys (IR kinase residues 1142-1153) efficiently inhibited IR autophosphorylation of both PM and EN receptors, Tris phosphorylation of beta-subunit regulatory tyrosines was unlikely. These results may be explicable by a dephosphorylation-dependent activation of IR kinase, as seen with the src family of tyrosine kinases.

Amino Acid Sequence↗

PubMed1992

Melanotropic activity of gamma MSH peptides in melanoma cells.

We studied the pigmentary activity of the peptides gamma 1, gamma 2 and gamma 3 melanocyte stimulating hormone (MSH), which differ in the structure of their C-termini, using hamster and mouse melanoma cell lines responsive to beta-MSH by increasing tyrosinase activity. Gamma 1-MSH alone or in combination with beta-MSH had no effect on either cell line. Gamma 2-MSH alone was biologically inactive but potentiated beta-MSH stimulation of tyrosinase activity. Gamma 3-MSH at high concentration (10 microM) induced tyrosinase activity and dendrite formation in the hamster melanoma line. When added together with beta-MSH, gamma 3-MSH partially inhibited the tyrosinase activity response to beta-MSH. Thus, gamma-MSH peptides have low intrinsic melanotropic activity in mammalian melanoma cells; the specific pigmentary responses appear to be affected by the structure of the C-terminal portion.

Amino Acid Sequence↗

PubMed1992

Localization of the heparin binding site of follistatin.

To define the heparin-binding site of follistatin, the reduced and S-carboxymethylated recombinant human follistatin containing 288 amino acids was digested by Staphylococcus aureus V8. The digested product was subjected to sulfate cellufine column chromatography and the adsorbed peptide fragments eluted with a stepwise gradient of sodium chloride. The recovered column fractions were further purified by reversed-phase high-performance liquid chromatography (HPLC) and the HPLC peaks subjected to amino-terminal sequence analysis. All of the sulfate cellufine-retarded peptide fragments gave the same N-terminal amino acid sequence, which started at residue-68 of human follistatin, suggested that those fragments starting from residue-68 contain the heparin binding site. The multiple fragments might represent the oxidized, non-glycosylated or glycosylated forms of follistatin(68-113) resulting from the V8 digestion. A synthetic peptide corresponding to the region having the amino acid sequence 72-86 of follistatin was able to bind both heparin and sulfate cellufine, as well as compete with recombinant follistatin for binding to heparin. These findings further define the location of the heparin and heparan sulfate-binding site of follistatin at the basic amino acid-rich region comprising the amino acid sequence Lys75-Lys-Cys-Arg-Met-Asn-Lys-Lys-Asn-Lys-Pro-Arg86.

Amino Acid Sequence↗

PubMed1992

Regulation of pulsatile gonadotropin secretion by estrogen, inhibin, and follistatin (activin-binding protein) in ovariectomized rats.

The following study was conducted to examine the effects of estrogen and polypeptides, given either alone or in combination, on pulsatile gonadotropin secretion. One week after ovariectomy, rats received s.c. injections of oil or various doses (0.5, 5, 20 micrograms) of estradiol benzoate (EB) followed 1 day later by i.v. administration of 60 micrograms purified porcine follistatin, 10 micrograms recombinant inhibin, or the appropriate vehicle. Four hours after injection of the nonsteroids, blood was collected at 10-min intervals for 2 h, and the effects on pulsatile hormone release were assessed. Administration of EB alone dose-dependently suppressed mean and trough (lowest point between two pulses) FSH levels and all parameters of pulsatile LH release. Both follistatin and inhibin at the doses employed suppressed mean FSH levels to an equivalent extent (40%). Follistatin, but not inhibin, suppressed FSH pulse amplitude, while neither polypeptide alone influenced FSH pulse frequency or any parameter of pulsatile LH release. The effects of follistatin and EB on mean FSH levels were additive at all EB doses, whereas the effects of inhibin and EB were additive only at the middle EB dose. Follistatin in combination with the lowest EB dose significantly suppressed mean LH levels. These studies are the first to demonstrate that combined treatment with estrogen and the nonsteroids follistatin and inhibin is more efficacious in suppressing FSH release than treatment with either agent alone, thereby indicating that both steroids and nonsteroids are probably important in the physiological regulation of FSH secretion in rats. The additive effects of these compounds on FSH secretion could form the basis for exploring novel contraceptive interventions.

Animals↗

PubMed1992

Gonadotropin and cAMP modulation of IGE binding protein production in ovarian granulosa cells.

Porcine granulosa cells (GC) produce insulin-like growth factor (IGF) binding protein (BP)-3 and IGFBP-2 in culture. A gonadotropin, follicle-stimulating hormone (FSH), dramatically inhibited GC production of these IGFBPs in control cultures and in cultures stimulated by insulin plus epidermal growth factor (EGF) or IGF-I plus EGF. Stimulators of adenylate cyclase (forskolin, cholera toxin) and a derivative of adenosine 3',5'-cyclic monophosphate (cAMP), 8-bromoadenosine 3',5'-cyclic monophosphate, inhibited IGFBP synthesis in a manner similar to FSH. In contrast, the antagonist of cAMP action, (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS], significantly stimulated production of IGFBP-3 and IGFBP-2 compared with controls. This stimulatory effect of (R)-p-cAMPS was counteracted by cotreatment with FSH in a dose-dependent manner. Finally, treatment of GC cultures with FSH plus 3-isobutyl-1-methylxanthine resulted in a significant reduction in cellular content of mRNA coding for IGFBP-3 with no change in IGFBP-2 mRNA. In summary, agents that elevate intracellular cAMP were found to mimic the effects of FSH on IGFBP production.

Animals↗

PubMed1992

Cyclic changes in insulin-like growth factor-binding protein-4 messenger ribonucleic acid in the rat ovary.

We have previously shown that the mRNA for insulin-like growth factor-binding protein-4 (IGFBP-4) is present in adult rat ovaries, being localized predominantly to granulosa cells of atretic follicles. Now we have considered the following questions. What class of atretic follicles expresses IGFBP-4 mRNA? How does IGFBP-4 mRNA expression change during the estrous cycle? In keeping with our earlier work, a strong hybridization signal for IGFBP-4 mRNA was present in subpopulations of follicles throughout the estrous cycle. In all cases, the hybridization signal was localized to granulosa cells. Among the various types of follicles, IGFBP-4 mRNA was present almost exclusively in atretic graafian (antral) follicles. Morphologically, the outer layer of granulosa cells was positive, while cells in the cumulus oophorous were negative. By Northern analysis and in situ hybridization, the levels of IGFBP-4 mRNA were found to change over the estrous cycle. At 1000 h on proestrus (before the LH/FSH surge), the hybridization signal was relatively weak, being restricted in some (but not all) atretic Graafian follicles. At 2000 h on proestrus, (after the LH/FSH surge), essentially all atretic Graafian follicles were strongly positive for the message. The pattern of hybridization was similar at 0200 h on estrus, but the signal was less intense. At 1000 h on estrus, the hybridization signal was variable, ranging from very strong to weak or undetectable in atretic follicles. At this stage, however, the highest levels of IGFBP-4 mRNA were measured by Northern analysis; interestingly, a strong signal became apparent in the stromal cells. On diestrous day 1, the message levels decreased, and the signal was restricted to some atretic follicles. On diestrous day 2, the hybridization signal was very weak. There was virtually no detectable IGFBP-4 mRNA in any healthy follicle. In summary, we found that IGFBP-4 mRNA is 1) not detected in healthy dominant follicles; 2) localized almost exclusively to atretic Graafian follicles, except on estrus when it also appears in stromal cells; 3) localized predominantly to the mural granulosa cells in atretic follicles; and 4) undergoes changes during the cycle, being most prominent around estrous morning. The possibility that IGFBP-4 plays a role in the cyclic destruction of cohort Graafian follicles at estrus, perhaps by mechanisms involving hormones, is discussed.

Animals↗

PubMed1992

Expression of messenger RNA for insulin-like growth factors and insulin-like growth factor binding proteins by experimental breast cancer and normal breast tissue in vivo.

We report the expression of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) by breast cancer cells and normal breast tissue in vivo. N-nitrosomethyl-urea (NMU)-induced rat mammary tumors synthesize mRNAs for IGF-II and IGFBP-2, -3, and -4. In contrast, normal lactating breast contains only IGFBP-2 and IGF-II messages; IGFBP-3 and -4 mRNAs are absent in this tissue. IGF-I and IGFBP-1 mRNAs are not expressed in either NMU tumors or in normal breast. This is the first report of in vivo expression of IGFBPs and IGF-II messages in breast tumors.

Animals↗

PubMed1992

Localization of insulin-like growth factor-binding protein-5 messenger ribonucleic acid in rat ovaries during the estrous cycle.

To investigate the potential role of insulin-like growth factor-binding protein-5 (IGFBP-5) in ovarian physiology, we employed in situ hybridization and Northern analysis to localize IGFBP-5 mRNA in rat ovaries during the estrous cycle. By Northern analysis, the mRNA was abundant at all stages of the cycle. Two species of mRNAs were detected, with sizes of 6.0 and 1.8 kilobases, respectively. The relative amounts of the two transcripts changed throughout the cycle. By in situ hybridization, IGFBP-5 mRNA was expressed in only a few cell types: 1) granulosa cells of some atretic follicles, 2) some secondary interstitial cells, 3) some corpora lutea, and 4) the surface epithelium. The levels of message in both the granulosa and secondary interstitial cells changed over the cycle. At 1000 h on proestrus (before the LH/FSH surge), the message was expressed in only a few follicles. Interestingly, all were small atretic preantral (200-250 microns) follicles. At 2000 h on proestrus (after the LH/FSH surge), the IGFBP-5 mRNA was more abundant; now almost every atretic preantral follicle showed a strong hybridization signal. At 0200 and 1000 h on estrus, the mRNA appeared for the first time in granulosa cells of some atretic antral follicles and in secondary interstitial cells. Hence, virtually all atretic follicles, preantral and antral, now showed IGFBP-5 gene expression. In contrast to that on proestrus and estrus, the hybridization signal on diestrous days 1 and 2 was much less prominent and was found in only a few atretic preantral follicles. Throughout the cycle, IGFBP-5 mRNA was evident in some corpora lutea, but it was not particularly prominent. Abundant IGFBP-5 mRNA was evident in the surface epithelium, and no change was detected over the cycle. Dominant follicles were devoid of IGFBP-5 mRNA. In conclusion, this paper presents the first evidence that the IGFBP-5 gene is expressed in the adult rat ovary. The IGFBP gene is expressed in a cell-specific manner, e.g. in atretic granulosa, secondary interstitial cells, corpora lutea, and the surface epithelium, and the stage of the cycle significantly affected message levels, especially in atretic granulosa and secondary interstitial cells around estrous morning. These findings suggest that IGBP-5 may be an autocrine/paracrine regulator of ovarian physiology, particularly in relation to preantral follicle atresia.

Animals↗

PubMed1992

Sensitive colorimetric bioassays for insulin-like growth factor (IGF) stimulation of cell proliferation and glucose consumption: use in studies of IGF analogs.

We have established two in vitro bioassay systems for quantification of insulin-like growth factor (IGF) bioactivity. The first assay was used to quantitate mitogenic activity and the second was used to quantitate metabolic activity. Both assays use BALB/c 3T3 fibroblasts grown under serum-free conditions; detection of bioactivity in assays was performed colorimetrically and did not require the use of radioisotopes. The mitogenic bioassay, which requires 48 h for detection, quantitates changes in cell number and provides an index for determining the mitogenic activity of growth factors. Changes in cell number were measured by the enzymatic reduction of exogenously added MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] to MTT-formazan by mitochondrial enzymes, which was directly correlated to cell number. The metabolic bioassay, which requires 22 h for detection, measures glucose consumption by detecting changes from the initial glucose concentration of conditioned medium after addition of various growth factors. When appropriate standards were established for these bioassays, they demonstrated a high level of reproducibility (coefficients of variation were 0.085-0.096 for the mitogenic bioassay and 0.120-0.191 for the metabolic bioassay). Both assays can be performed in 96-well microtiter plates, without the use of radioisotopes, or the limitations of conventional glucose, amino acid, or thymidine incorporation studies. In initial experiments for assay specificity, epidermal growth factor had no measurable effect in either assay. However, IGF-I, IGF-II, and insulin demonstrated effects on both metabolism and mitogenesis. In the case of the mitogenic bioassay, the maximum mitogenic activation by these growth factors was approximately 180% of control, and these factors demonstrated parallel sigmoidal dose-response curves, ranging from 0.02-2 ng/ml for IGF-I and from 2-200 ng/ml for both IGF-II and insulin. In the metabolic bioassay, in contrast to the mitogenic bioassay, insulin showed a dose-response curve whose shape was different from those of IGF-I and IGF-II. IGF-I and IGF-II stimulated glucose consumption in dose-dependent ranges of 0.02-3 ng/ml and 0.4-40 ng/ml, respectively. However, the dose-response effect of insulin was wider, ranging from 0.1-2000 ng/ml. When these assays were used to measure the bioactivity of IGF analogs, a des(1-3)-IGF-I, which has decreased affinity for IGF binding proteins, demonstrated activity equivalent to IGF-I, a [Leu27]IGF-II, which has markedly diminished affinity for the type 1 IGF receptor, exhibited approximately 0.07% of the potency of IGF-I and 1% of the potency of IGF-II.

3T3 Cells↗

PubMed1992

Expression of insulin-like growth factor-binding protein-2 and -3 messenger ribonucleic acid in the porcine ovary: localization and physiological changes.

Insulin-like growth factor-binding protein (IGFBP)-2 and -3 are the most prevalent IGFBPs in porcine follicular fluid, as determined on ligand blots, but little is known about the localization and regulation of their synthesis in vivo. This study was designed to investigate the localization and cyclic regulation of the mRNA for these two IGFBPs in the porcine ovary, RNA was extracted from whole ovaries morphologically classified as immature, preovulatory, and luteal. Northern hybridization analysis of this RNA showed no significant difference in the expression of IGFBP-2 mRNA in these ovaries (OD for preovulatory, luteal, and immature ovaries, 0.076 +/- 0.01, 0.071 +/- 0.01, and 0.10 +/- 0.008/micrograms RNA, respectively). IGFBP-3 mRNA was not different in immature and preovulatory ovaries, but was 10-fold greater (P less than 0.025) in luteal ovaries. Northern analysis of RNA extracted from ovaries also showed no significant change in IGFBP-2 mRNA on days (d) 11, 16, and 21 of the estrous cycle. IGFBP-3 mRNA tended to decrease between d11-16 with the onset of luteal regression and was significantly decreased in d21 preovulatory ovaries to 22% of the values in d11 ovaries. Granulosa, thecal, and luteal cells were also analyzed for IGFBP mRNA. IGFBP-2 mRNA was most abundant in granulosa cells, lower in thecal cells, and lowest in luteal cells. No IGFBP-3 mRNA could be detected in granulosa cells, and luteal cells expressed 15- to 63-fold greater levels than thecal cells. These results show that IGFBP-2 and -3 mRNAs are expressed in specific ovarian cell types and that their expression appears to be independently regulated during the reproductive cycle. This provides further evidence for the importance of these proteins as paracrine/autocrine regulators of ovarian function.

Actins↗

PubMed1992

Expression of inhibin beta A and beta B, follistatin and activin-A receptor messenger ribonucleic acids in the rat seminiferous epithelium.

The expression of inhibin beta A and beta B subunits, follistatin, and activin-A receptor messenger RNA (mRNAs) in different stages of rat seminiferous epithelial cycle was analyzed by in situ hybridization in order to understand their role in the regulation of spermatogenesis. Inhibin beta A mRNA was expressed in Sertoli cells in a highly stage-specific manner. The mRNA levels started to accumulate in Sertoli cells at stage VIII of the cycle and were highly expressed during stages IX-XI. Follistatin mRNA expression was identical to that of inhibin beta A, while inhibin beta B mRNA was maximally expressed in Sertoli cells at stages XIII-III. Low expression was found in stages VII-VIII. Activin-A receptor mRNA was localized mainly in spermatogenic cells. Maximal expression was seen in late primary spermatocytes at stages XIII-XIV and in early round spermatids at stages I-IV. A low even expression by Sertoli cells was also seen. Inhibin beta A and follistatin mRNAs were coexpressed in stage IX-XI Sertoli cells, suggesting close interplay between these molecules. The pattern of inhibin beta B mRNA expression was similar to that of inhibin alpha-mRNA. Localization of activin-A receptor mRNA in spermatogenic cells suggests that activin may influence meiotic divisions and early spermiogenesis.

Activin Receptors↗

PubMed1991

Site-specific mutagenesis of human follistatin.

Follistatin is a monomeric protein originally discovered in ovarian follicular fluid as a suppressor of pituitary follicle-stimulating hormone (FSH) secretion, and later identified as a binding protein for activin. To explore the role of the Asn-linked carbohydrate chains on the follistatin molecule in regard to the inhibition of FSH secretion and activin binding ability, site-specific mutations were introduced at either or both of the two potential Asn-linked glycosylation sites of human follistatin with 315 amino acids (hFS-315). The three types of follistatin mutants were expressed individually in Chinese hamster ovary cells. When tested for their ability to inhibit FSH secretion and to bind activin, each mutant was found to have a similar property as the non-mutated recombinant hFS-315, suggesting that glycosylation of the follistatin molecule has no effect in these functions. However, a two amino acid insertion in between the second and the third amino acid residues in hFS-315 caused the resulting compound to lose completely its inhibitory activity on FSH secretion from the pituitary as well as its binding ability to activin. This finding suggests that the amino-terminal region of the follistatin molecule is critical for both of these functions.

Activins↗

PubMed1991

Brain corticotropin-releasing hormone increases arousal in stress.

The effect of restraint stress on pentobarbital-induced sleeping time was examined in rats. Restraint for 60 and 75 min significantly shortened pentobarbital-induced sleeping time. The shortening of sleeping time by restraint was completely reversed by intracerebroventricular (i.c.v.) administration of alpha-helical CRH(9-41), a corticotropin-releasing hormone (CRH) receptor antagonist. In conjunction with our previous finding that i.c.v. administration of CRH shortens pentobarbital-induced sleeping time, the results suggest that restraint stress increases arousal through brain CRH.

Animals↗

PubMed1991

Identification of five different insulin-like growth factor binding proteins (IGFBPs) from adult rat serum and molecular cloning of a novel IGFBP-5 in rat and human.

Five different insulin-like growth factor binding proteins (IGFBPs) were isolated from adult rat serum using gel filtration, ligand affinity chromatography, and two steps of reversed-phase high performance liquid chromatography. Three of them were identified as IGFBP-2, -3, and -4 by their amino-terminal amino acid sequences. One of the remaining two proteins was the rat homologue of the partially characterized IGFBP isolated originally from human cerebrospinal fluid, while the other appeared to be a novel member of the IGFBP family. IGFBP-1 was not found in the adult rat serum under our experimental procedures. cDNAs encoding the novel IGFBP were isolated and characterized from a rat ovary and a human placenta library. The mature protein predicted for both species contained 252 amino acids including 18 cysteines that were located in the homologous positions as IGFBP-1, -2, -3, and -4. We propose to name this protein IGFBP-5. Northern analysis of IGFBP-5 mRNA in rat tissues demonstrated that transcription of this gene is highly active in kidney, although the mRNA was detectable in all tissues examined. Alignment of the amino acid sequences of the five rat IGFBPs revealed a 47-60% similarity, indicating that their individual genes diverged from a single ancestral gene by successive gene duplication in a short time frame during evolution. The chromosomal localizations of IGFBP-1, -2, -3, -4, and -5 genes in human have been determined using polymerase chain reaction on somatic cell hybrid DNAs of human and hamster, and the results showed that they were located on chromosomes 7, 2, 7, 17, and 5, respectively.

Amino Acid Sequence↗

PubMed1991

In vitro release of growth hormone-releasing factor (GRF) from the hypothalamus: somatostatin inhibits GRF release.

The manner of release of growth hormone-releasing factor (GRF) from the rat hypothalamus was studied in a perifusion system using a highly sensitive radioimmunoassay for rat GRF. The recovery of GRF in this system was 50-60%. The release of GRF from the rat hypothalamic blocks was almost stable for 20-240 min after the start of the perifusion and was stimulated by depolarization induced by high K+ concentration. The release of GRF was inhibited by somatostatin at concentrations of 10(-11) to 10(-8) M with maximum inhibition to 52.5% of the basal release at a concentration of 10(-9) M. These results suggest that this system is useful in studying the regulatory mechanism of GRF release and that, in addition to its action on the pituitary, somatostatin appears to act at the level of the hypothalamus in inhibiting GRF release in the regulation of GH secretion.

Animals↗

PubMed1991

Phosphorylation of basic fibroblast growth factor by purified protein kinase C and the identification of a cryptic site of phosphorylation.

We have further characterized the protein kinase C (PK-C) dependent phosphorylation of basic fibroblast growth factor (FGF). Intact recombinant basic FGF and a series of ten peptide fragments of basic FGF were phosphorylated by PK-C and the products were analyzed by SDS-PAGE and autoradiography. As expected, peptide fragments containing the known site of phosphorylation (Ser64) are substrates for phosphorylation. Surprisingly however, peptides containing the receptor binding domain of the mitogen [basic FGF(106-115)] are also phosphorylated. An examination of this sequence reveals the presence of a consensus sequence (Ser108-Ala109-Lys110) that mediates the reaction. Accordingly, all peptides that contain the core amino acids basic FGF(106-111) are substrates for phosphorylation. Peptide mapping of basic FGF confirms that Ser64 is the primary site of phosphorylation, suggesting that Ser108 is a cryptic consensus sequence. Because basic FGF is metabolized to sequence specific fragments after its binding and internalization into target cells, this cryptic site may in fact be phosphorylated in vivo.

Animals↗

PubMed1991

The effects of chronic central administration of corticotropin-releasing factor on food intake, body weight, and hypothalamic-pituitary-adrenocortical hormones.

The effects of chronic central administration of corticotropin-releasing factor (CRF) on food intake, body weight, and hypothalamic-pituitary-adrenocortical hormones were investigated in rats. The infusion of ovine CRF at doses of 0.3 and 1.0 microgram/h continuously induced decrease in food intake and a suppression of body-weight gain for 7 days. The inhibition of body weight gain induced by CRF could not be accounted for solely by a decreased food intake since the suppression of body-weight gain in CRF-infused rats was significantly greater than that observed in rats which received the same amount of food as the CRF-infused rats. The content of proopiomelanocortin (POMC) -derived peptides in the anterior lobe of the pituitary as well as the plasma levels of ACTH and corticosterone (B) were significantly elevated in CRF-treated rats, and the CRF content in the hypothalamus was significantly decreased. These results suggest that chronic intracerebroventricular (icv) administration of CRF stimulates the synthesis and secretion of POMC-related peptides in the pituitary and suppresses food intake accompanied by inhibition of body weight gain. The results are similar to clinical and laboratory findings observed in patients with stress-induced anorexia.

Adrenocorticotropic Hormone↗

PubMed1991

Interleukin-1 inhibits stress-induced gastric erosion in rats.

The effect of interleukin (IL)-1 on the occurrence of stress-induced gastric erosions was examined in rats. The intracerebroventricular (icv) administration of IL-1 beta significantly inhibited the occurrence of water-immersion restraint stress-induced gastric erosion at doses of 200 ng, 500 ng and 1 microgram, whereas the intravenous (iv) administration of IL-1 beta altered the occurrence of gastric erosion only at a dose of 1 microgram. The inhibitory effect of IL-1 alpha icv administered on the occurrence of gastric erosion was found only at a dose of 1 microgram. The inhibitory effect of IL-1 beta icv administered on the occurrence of stress-induced gastric erosion was not influenced by icv administration of alpha-helical CRF(9-41), a corticotropin-releasing factor (CRF) receptor antagonist. Indomethacin completely blocked the inhibitory action of IL-1 beta icv administered on stress-induced gastric erosion. It is concluded from these results that IL-1 acts mainly in the central nervous system to inhibit the occurrence of stress-induced gastric erosion and that the IL-1 beta-induced inhibition of gastric erosion is mediated by prostaglandin in a manner that is independent of brain CRF.

Animals↗