Elevated dietary salt suppresses renin secretion but not thirst evoked by arterial hypotension in rats

Increased dietary salt intake was used as a nonpharmacological tool to blunt hypotension-induced increases in plasma renin activity (PRA) in order to evaluate the contribution of the renin-angiotensin system (RAS) to hypotension-induced thirst. Rats were maintained on 8% NaCl (high) or 1% NaCl (standard) diet for at least 2 wk, and then arterial hypotension was produced by administration of the arteriolar vasodilator diazoxide. Despite marked reductions in PRA, rats maintained on the high-salt diet drank similar amounts of water, displayed similar latencies to drink, and had similar degrees of hypotension compared with rats maintained on the standard diet. Furthermore, blockade of ANG II production by an intravenous infusion of the angiotensin-converting enzyme inhibitor captopril attenuated the hypotension-induced water intake similarly in rats fed standard and high-salt diet. Additional experiments showed that increases in dietary salt did not alter thirst stimulated by the acetylcholine agonist carbachol administered into the lateral ventricle; however, increases in dietary salt did enhance thirst evoked by central ANG II. Collectively, the present findings suggest that hypotension-evoked thirst in rats fed a high-salt diet is dependent on the peripheral RAS despite marked reductions in PRA.     

Continuous infusion of GnRH reduces the LH response to an intravenous GnRH injection but does not inhibit endogenous LH secretion in cows

Plasma LH concentrations were monitored in 6 Hereford X Friesian suckled cows at about 80 days post partum, before and during a 14-day period of continuous s.c. infusion of GnRH (20 micrograms/h). Blood samples were collected at 10-min intervals on Days -2, -1, 1, 2, 3, 4, 7, 10, 13 and 14 (Day 1 = start of infusion). Plasma LH concentrations rose from mean pretreatment levels of 1.3 +/- 0.20 ng/ml to a maximum of 17.1 +/- 3.09 ng/ml within the first 8 h of GnRH infusion, but returned to pretreatment levels by Day 2 or 3. In 4/6 animals, the initial increase was of a magnitude characteristic of the preovulatory LH surge. In all animals, an i.v. injection of 10 micrograms GnRH, given before the start and again on the 14th day of continuous infusion, induced an increase in LH concentrations but the increase to the second injection was significantly (P less than 0.01) less (mean max. conc. 6.4 +/- 0.76 and 2.3 +/- 0.19 ng/ml). Mean LH concentrations (1.0 +/- 0.08, 1.1 +/- 0.08 and 0.9 +/- 0.06 ng/ml) and LH episode frequencies (3.3,4.3 and 3.2 episodes/6 h) did not differ significantly on Days -2,7 and 13. However, the mean amplitude of LH episodes was significantly lower (P less than 0.05) on Day 13 (1.3 +/- 0.10 ng/ml) than on Day -2 (1.8 +/- 0.16 ng/ml). Therefore, although the elevation in plasma LH concentrations that occurs in response to continuous administration of GnRH is short-lived and LH levels return to pre-infusion values within 48 h of the start of infusion, these results show that the pituitary is still capable of responding to exogenous GnRH, although the LH response to an i.v. bolus injection of GnRH is reduced. In addition, this change in pituitary sensitivity is not fully reflected in endogenous patterns of episodic LH secretion.     

Gastrin-releasing peptide suppresses independent but not intraoral intake.

Independent and intraoral intake tests have been used to separate the effects of various substances on the appetitive and consummatory phases of ingestive behavior. This study compared the ability of gastrin-releasing peptide1-27 (GRP) to suppress intraoral intake of nutrient solutions versus independent intake of the same solutions from a bottle. In a series of experiments, adult male Sprague Dawley rats implanted with anterior sublingual chronic intraoral catheters were injected intraperitoneally with saline control or 28 microg/kg GRP before 20-min intraoral and 20-min one-bottle intake tests of a sucrose (0.1 M) and milk solution (1.2 kcal/ml). GRP potently reduced independent intake of both sucrose and milk from a bottle but had no significant effect on intraoral intake of either solution. From these results, we conclude that GRP affects appetitive-related aspects of the feeding process to reduce food intake.     

Triiodothyronine induces a transferable factor which suppresses TSH secretion in cultured mouse thyrotropic tumor cells

Modulation of TSH release from mouse thyrotropic tumor cells was studied. T₃ (1 nM) inhibited basal TSH release, while 6 nM T₃ blocked TRH-induced TSH release. Prior exposure of cells to actinomycin or cycloheximide prevented T₃ from suppressing basal and TRH-induced TSH release. The TSH-suppressive activity from T₃-treated cells was extracted and exposure of untreated thyrotropic cells to this material resulted in suppression of TSH release. The data suggest that T₃ suppression of TSH is mediated by formation of an inhibitory protein in thyrotropic cells.     

Synthesis and secretion of GnRH

Comprehensive studies have provided a clear understanding of the effects of gonadal steroids on the secretion of gonadotropin releasing hormone (GnRH), but some inconsistent results exist with regard to effects on synthesis. It is clear that regulation of both synthesis and the secretion of GnRH are effected by neurotransmitter systems in the brain. Thus, steroid regulation of GnRH synthesis and secretion can be direct, but the predominant effects are transmitted through steroid-responsive neuronal systems in various parts of the brain. There is also emerging evidence of direct effects on GnRH cells. Overriding effects on synthesis and secretion of GnRH can be observed during aging, in undernutrition and under stressful situations; these involve various neuronal systems, which may have serial or parallel effects on GnRH cells. The effect of aging is accompanied by changes in GnRH synthesis, but comprehensive studies of synthesis during undernutrition and stress are less well documented. Altered GnRH and gonadotropin secretion that occurs in seasonal breeding animals and during the pubertal transition is not generally accompanied by changes in GnRH synthesis. Secretion of GnRH from the brain is a reflection of the inherent function of GnRH cells and the inputs that integrate all of the central regulatory elements. Ultimately, the pattern of secretion dictates the reproductive status of the organism. In order to fully understand the central mechanisms that control reproduction, more extensive studies are required on the neuronal circuitry that provides input to GnRH cells.     

Dexamethasone suppresses pituitary-adrenal but not behavioral effects of centrally administered CRF

Intracerebral ventricular (icv) administration of corticotropin-releasing factor (CRF) significantly enhances the expression of stress-related behaviors in the rat and also activates the pituitary-adrenal system. The pituitary-adrenal response can be blocked by pretreatment of animals with dexamethasone. The behavioral effects (motor activation, increased grooming and decreased eating) on the other hand are resistant to suppression by dexamethasone. The independence of the behavioral effects from activation of the pituitary-adrenal axis suggests that stress-induced release of CRF could contribute to behavioral alterations even in the presence of high concentrations of endogenous steroids.     

Cell transformation by kFGF requires secretion but not glycosylation

The Kfgf gene, which encodes a member of the fibroblast growth factor family, was originally discovered by assaying human tumor DNA for dominantly transforming oncogenes. The 22-kD kFGF product contains a single site for asparagine-linked glycosylation and an amino-terminal signal peptide for vectorial synthesis into the endoplasmic reticulum and eventual secretion. To determine whether these features are necessary for transformation, we have constructed mutants of kFGF that are impaired for glycosylation or secretion. All mutants retained the ability to induce DNA synthesis when added to quiescent cells, and the absence of glycosylation had no appreciable effect on the transformation efficiency on NIH3T3 cells. In contrast, mutants of kFGF that remain in the cytoplasm or are retained in the secretory pathway, through addition of a KDEL motif, score negative in standard transformation assays. Since transformation by either the glycosylated or unglycosylated form of kFGF can be reversed by addition of suramin, the data imply that secretion of kFGF, or surface localization of the ligand/receptor complex, is a prerequisite for transformation.     

Homotypic cell contact enhances insulin but not glucagon secretion

Intra-islet interactions influence beta-cell function, and disruption of islet architecture results in a reduction in glucose-induced insulin secretion, whereas re-aggregation improves secretory responsiveness. Our studies on MIN6 cells have shown that by configuring beta-cells as three-dimensional islet-like structures there is a marked improvement in glucose-induced insulin secretion compared to that of their monolayer equivalents. In the present study, we have used the mouse glucagon-secreting alphaTC1 cell line to see whether homotypic interactions are important in the regulation of glucagon secretion from alpha-cells. We found no significant difference in the secretory responses of alphaTC1 cells maintained as monolayers or as cell clusters. We also found that different cell adhesion molecules are involved in cell interactions between alpha- and beta-cells; MIN6 cells express ECAD, whereas alphaTC1 cells express NCAM. ECAD is necessary for cell cluster formation by MIN6 cells but not by alphaTC1 cells, whereas NCAM is not needed for the formation of cell clusters in either cell line.     

Prolactin secretion in testicular cancer patients

The role of prolactin (PRL) in testicular function and in its disorders is still obscure. To draw some preliminary conclusions on the relation between the PRL and testis cancer, we assessed the PRL response to thyrotropin-releasing hormone (THR) in 15 patients with testicular cancer (8 seminoma; 6 nonseminoma; 1 leydigioma), and in 11 healthy male subjects as controls. The results showed that 5/15 cancer patients gave no PRL response to TRH; 4 of them had a nonseminoma and the fifth a seminomatous testis carcinoma. Patients with nonseminoma had significantly lower mean peak values of PRL after TRH than controls or patients with seminoma. The biological significance of the altered PRL response to TRH in testicular carcinoma has still to be established.     

Trifluoperazine inhibits thyrotropin-releasing hormone-stimulated TSH secretion

In previous work changes of the thyrotropic secretion after administration of some substances affecting the calcium content in the cytosol were demonstrated. The object of the present investigation was to assess the hormonal response to the administration of trifluoperazine, a psychopharmaceutical preparation, the main mechanism of its action being the inactivation of the cytosol receptor for the calcium signal - calmodulin. The poor utilization of intracellular calcium of the secretory cell is then the factor which inhibits secretion proper. The thyrotropic secretory reserve (delta TSH) was assessed in the same subjects before and after trifluoperazine administration by the TRH test as the difference of values at rest and TRH-stimulated TSH levels during the 20th, 30th, 40th and 60th minute following intravenous administration of 200 micrograms TRH. It was revealed that this calmodulin antagonist administered for one week in amounts of 6-12 mg per day by mouth significantly inhibits the secretory response of TSH to TRH in healthy subjects during the 20th and 40th min. (P less than 0.05). The reproducibility of the TRH test repeated in a group of subjects not treated with trifluoperazine, however, under equal conditions and after the same time intervals as in the experiment with trifluoperazine was very satisfactory and thus physiological inhibition caused by repeated TRH administration could be ruled out. The inhibition of the secretory TSH response to TRH can be therefore considered the consequence of the direct effect of trifluoperazine on the thyrotropic secretory mechanism. Trifluoperazine significantly reduced serum calcium levels and raised phosphate levels, while it did not affect the blood levels of magnesium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early-cleavage is a reliable predictor for embryo implantation in the GnRH agonist protocols but not in the GnRH antagonist protocols

Background  

To test if early-cleavage was a strong predictor of pregnancy in patients receiving either a GnRH agonist long protocol or a GnRH antagonist protocol for in-vitro fertilization treatment (IVF) and intracytoplasmic sperm injection (ICSI).     

Plasmodium chabaudi: estradiol suppresses acquiring, but not once-acquired immunity.

This study investigates the effect of estradiol (E) on self-healing of Plasmodium chabaudi malaria in mice of the inbred strain C57BL/10. Our data show: (1) Female mice and male castrates are capable of self-healing infections when challenged with 10(6) P. chabaudi-infected erythrocytes. Self-healing is completely suppressed after pretreatment of mice with 12 micrograms E injected sc twice a week for 3 weeks. (2) The suppressive effect of E is prevented by the estrogen receptor blockers tamoxifen and clomiphene. (3) The nonsteroidal E-agonist diethylstilbestrol (DES) also suppresses self-healing. This suppressive DES effect is prevented by tamoxifen. (4) In mice immune to P. chabaudi, neither survival rate nor the course of parasitemia is affected by E, even at 10-fold higher E doses. Our data suggest that the immunosuppressive action of E is a specific genomic effect, i.e., E-induced gene products prevent the development of protective immunity against P. chabaudi.     

Ascorbic acid suppresses the deconjugation of noradrenaline but not dopamine in plasma

The characteristics of hydrolysis of sulfoconjugated noradrenaline (NA) and dopamine (DA) in plasma using sulfatase were investigated. Ascorbic acid has been used as an antioxidant during the hydrolysis of conjugated NA or DA. Hydrolysis of NA sulfates was considerably inhibited by adding ascorbic acid (0.5-10 mM), and slightly inhibited by adding dithiothreitol (1-10 mM). In contrast, the hydrolysis of DA sulfates was not affected after either ascorbic acid or DTT treatment. On the basis of these findings, the levels of NA sulfates previously reported are found to be markedly lower than the actual levels of NA sulfates in human plasma.     

Experimental Mycoplasma pulmonis infection of rats suppresses humoral but not cellular immune response

Humoral antibody response to sheep red blood cells and cellular immune response to bovine serum albumin were studied in Mycoplasma pulmonis infected, adult, male Sprague-Dawley rats. The hemagglutinating antibody response to sheep red blood cells was evaluated at 0, 3, 5, 7, 14, 21 and 28 days postinfection. Antibody titers during all days postinfection were depressed significantly (p less than 0.05) in infected rats as compared to noninfected controls. Cellular immune responses were evaluated by a delayed hypersensitivity response. Rats were sensitized at 0, 3, 5, 7, 14, 21 or 28 days postinfection with bovine serum albumin and challenged with heat aggregated bovine serum albumin 7 days later. Cell-mediated immune responses in infected rats were not significantly different at any point from controls. These results indicate that M. pulmonis infection in rats suppresses the humoral antibody response to sheep red blood cells, but not the cellular immune response to bovine serum albumin.     

24, 25-dihydroxycholecalciferol but not 25-hydroxycholecalciferol suppresses apolipoprotein A-I gene expression

AimsLigands for the vitamin D receptor (VDR) regulate apolipoprotein A-I (apo A-I) gene expression in a tissue-specific manner. The vitamin D metabolite 24, 25-dihydroxycholecalciferol (24, 25-(OH)₂D₃) has been shown to possess unique biological effects. To determine if 24, 25-(OH)₂D₃ modulates apo A-I gene expression, HepG2 hepatocytes and Caco-2 intestinal cells were treated with 24, 25-(OH)₂D₃ or its precursor 25-OHD₃.Main methodsApo A-I protein levels and mRNA levels were measured by Western and Northern blotting, respectively. Changes in apo A-I promoter activity were measured using the chlorampenicol acetytransferase assay.Key findingsTreatment with 24, 25-(OH)₂D₃, but not 25-OHD₃, inhibited apo A-I secretion in HepG2 and Caco-2 cells and apo A-I mRNA levels and apo A-I promoter activity in HepG2 cells. To determine if 24, 25-(OH)₂D₃ represses apo A-I gene expression through site A, the nuclear receptor binding element that is essential for VDRs effects on apo A-I gene expression, HepG2 cells were transfected with plasmids containing or lacking site A. While the site A-containing plasmid was suppressed by 24, 25-(OH)₂D₃, the plasmid lacking site A was not. Likewise, treatment with 24, 25-(OH)₂D₃ suppressed reporter gene expression in cells transfected with a plasmid containing site A in front of a heterologous promoter. Finally, antisense-mediated VDR depletion failed to reverse the silencing effects of 24, 25-(OH)₂D₃ on apo A-I expression.SignificanceThese results suggest that the vitamin D metabolite 24, 25-(OH)₂D₃ is an endogenous regulator of apo A-I synthesis through a VDR-independent signaling mechanism.