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Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-kappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated kinase 1/2.

Beyond their effects on central metabolic functions, leptin, resistin, and adiponectin have profound effects on a number of other physiologic processes, including immune function and inflammation. Although leptin, resistin, and adiponectin are produced in human placenta and adipose tissue, their immunoregulatory actions in these tissues are not known. Therefore, the aim of this study was to determine the effect of leptin, resistin, and adiponectin on the release of proinflammatory mediators in human placenta and sc adipose tissue. Samples were obtained from normal pregnancies at the time of cesarean section. Tissue explants (n = 5) were incubated in the absence (basal control) or presence of a leptin (1, 10, and 100 ng/ml), resistin (1, 10, and 100 ng/ml), and adiponectin (0.1 and 0.5 microg/ml). After 6 h incubation, the medium was collected, and the release of IL-1beta, IL-6, TNFalpha, prostaglandin (PG)F2alpha and PGE2 was quantified by ELISA. There was no effect of resistin on proinflammatory cytokine or prostaglandin release; however, leptin at 100 ng/ml and adiponectin at 0.1 and/or 0.5 microg/ml significantly increased the release of IL-1beta, IL-6, TNFalpha, and PGE2 from human placenta and adipose tissue. Although both leptin and adiponectin significantly increased PGF2alpha release from human placenta, there was no effect of these hormones on PGF2alpha release from adipose tissue. Furthermore, this leptin- and adiponectin-induced proinflammatory response could be abrogated by treatment with the antiinflammatory ERK1/2 MAPK inhibitor U0126, the peroxisomal proliferator-activated receptor-gamma ligand troglitazone, and the nuclear factor-kappaB inhibitor BAY 11-7082. Collectively, these data indicate that leptin and adiponectin activate proinflammatory cytokine release and phospholipid metabolism in human placenta and adipose tissue, and antiinflammatory agents can abrogate leptin- and adiponectin-induced inflammation.

Adiponectin↗

Urbanization and industrialization versus biological status of human populations.

The paper concerns the biological status of the Polish population. A comparison was made for inhabitants of towns, villages, and areas under different levels of industrialization and environmental pollution. It has been found that urban populations as compared with rural ones were characterized by a smaller number of children within a family, higher natural abortion rate, and higher infant mortality (estimated during the first 24 hours of life). An analysis of birth rate in three groups of birth weight has shown that rural habitats were more suitable for prenatal development than urban habitats, as a higher proportion of newborns had optimum body weight at birth in villages. It has been observed that the biological status of fetus (estimated as the body weight at birth) depended on the socio-economic conditions (a relatively high birth rate with optimum body weight in the first half of the 1970s, and a low birth rate in the years of the social crisis in Poland in 1981-82). Moreover, it has been found that in agricultural areas relatively little polluted (the Suwałki region), birth rate and total mortality were high, respiratory traits reached highest values, and blood pressure was low as compared with values of these traits in other areas of Poland. The inhabitants of industrial centers (Puchaczów, Bukowno) were exposed to heavier environmental pollution than the rural population, and at Puchaczów they were characterized by a short stature and low body weight. The seaside region (Jastarnia) was over-crowded and also affected by the pollution of the Puck Bay. Both these factors could account for a high mortality and emigration rate. Inhabitants of the areas being industrialized (Bełchatów) were characterized by a low total mortality, below average for infants, poor development of the respiratory system, but a high psychomotor fitness. In the city of Lódź and in Strzemieszyce, environmental pollution was very high, which was combined with a very high total mortality, and in Lódź also with a high infant mortality. In Strzemieszyce, the values of some physiological traits such as Hb and HR were increased.

Birth Weight↗

Sulfasalazine and BAY 11-7082 interfere with the nuclear factor-kappa B and I kappa B kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro.

There is much evidence to indicate a role for adipocytokines in insulin resistance and/or type 2 diabetes mellitus. In experimental models, oral salicylates, through their ability to interfere with the nuclear factor-kappa B (NF-kappa B) transcription pathway, have been demonstrated to reverse insulin resistance. The aim of this study was to investigate whether NF-kappa B regulates the release of adipocytokines in human adipose tissue and skeletal muscle. Human sc adipose tissue and skeletal muscle (obtained from normal pregnant women) were incubated in the absence (control) or presence of two NF-kappa B inhibitors sulfasalazine (1.25, 2.5, and 5 mm) and BAY 11-7082 (25, 50, and 100 microm). After an 18-h incubation, the tissues were collected, and NF-kappa B p65 DNA-binding activity and I kappa B kinase (IKK-beta) and insulin receptor-beta protein expression were assessed by ELISA and Western blotting, respectively. The incubation medium was collected, and the release of TNF-alpha, IL-6, IL-8, resistin, adiponectin, and leptin was quantified by ELISA. Treatment of adipose tissue and skeletal muscle with sulfasalazine and BAY 11-7082 significantly inhibited the release of IL-6, IL-8, and TNF-alpha; NF-kappa B p65 DNA-binding activity; and IKK-beta protein expression (P < 0.05, by Newman-Keuls test). There was no effect of sulfasalazine and BAY 11-7082 on resistin, adiponectin, or leptin release. Both sulfasalazine and BAY 11-7082 increased the adipose tissue and skeletal muscle expression of insulin receptor-beta. The data presented in this study demonstrate that the IKK-beta/NF-kappa B transcription pathway is a key regulator of IL-6, IL-8, and TNF-alpha release from adipose tissue and skeletal muscle. Control of the IKK-beta/NF-kappa B pathway may therefore provide an alternative therapeutic strategy for regulating aberrant cytokine release and thereby alleviating insulin resistance in type 2 diabetes mellitus.

Adiponectin↗

PCDD/F, PCB, HxCBz, PAH, and PM emission factors for fireplace and woodstove combustion in the San Francisco Bay region.

Emissions from residential fireplace and woodstove appliances burning fuels available from the San Francisco Bay area were sampled for polychlorinated dibenzodioxins and dibenzofurans (PCDDs/Fs), polychlorinated biphenyls (PCBs), hexachlorobenzene (HxCBz), particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), oxygenated PAHs, and the monosaccharide levoglucosan. Emission factors for these pollutants were determined, the first known characterization of this extent. Common California natural firewoods and manufactured artificial logs were tested under operating conditions intended to reflect domestic use patterns in the Bay area, which are primarily episodic burning for aesthetic reasons. Emission factors were determined by fuel type, fuel weight, mass emission rates, and energy output, highlighting differences between fuel and combustion facility type. Average PCDD/F emissions factors ranged from 0.25 to 1.4 ng toxic equivalency (TEQ)/kg of wood burned for natural wood fuels and 2.4 ng TEQ/kg for artificial logs. The natural wood emission factors are slightly lower than those which had been estimated for the U.S. inventory. Background-corrected PCBs emitted from woodstove/oak combustion (8370 ng/kg) are 3 orders of magnitude higher in mass than total PCDDs/Fs; however, their toxicity (0.014 ng TEQ/kg) is significantly lower. HxCBz emission factors varied from 13 to 990 ng/kg and were likely fuel- and appliance-specific. Relative PAH concentrations of particle-phase compounds and emission factors were consistent with others' findings. A total of 32 PAH compounds, ranging in concentration from 0.06 to 7 mg/kg, amounted to between 0.12 and 0.38% of the PM mass, depending on the wood and facility type. Preliminary analyses suggest relationships between wood combustion markers and PCDD/F levels.

Air Pollutants↗

Selected trace metals in oysters (Crassostrea iridescens) and sediments from the discharge zone of the submarine sewage outfall in Mazatlán Bay (southeast Gulf of California): chemical fractions and bioaccumulation factors.

Concentrations of Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn in the soft tissue of Crassostrea iridescens and the associated surface sediments (bulk and bioavailable metal concentrations) from an area influenced by a sewage outfall in Mazatlán Bay (southeast Gulf of California), were determined by atomic absorption spectrophotometry. Significant spatial differences in metal concentrations in both the bulk and bioavailable forms in the sediments were identified. An enrichment of Cu, Ni, Pb and Zn in sites located on a south-north transect was detected indicating a dominant influence of the sewage outfall toward the north. C. iridescens accumulated more Zn, Cu, Ni, Fe, Cd; and less Mn, Cr and Pb than were bioavailable in the sediments, as measured using conventional extraction analysis. The degree of enrichment and the bioavailable metal concentrations in the sediments of the south portion of Mazatlán Bay is discussed. The potential ability of C. iridescens as a biomonitor of metallic pollutants is postulated.

Animals↗

Variation of phytoplankton biomass and primary production in Daya Bay during spring and summer.

Environmental factors, phytoplankton biomass (Chl a) and primary production of two water areas in Daya Bay (Dapeng'ao Bay and Aotou Bay) were investigated during the transition period from spring to summer. Chl a ranged from 3.20 to 13.62 and 13.43 to 26.49 mg m(-3) in Dapeng'ao Bay and Aotou Bay respectively, if data obtained during red tides are excluded. Primary production varied between 239.7 and 1001.4 mg Cm(-2) d(-1) in Dapeng'ao Bay. The regional distribution of Chl a and primary production were mostly consistent from spring to summer in both bays. Seasonal transition characters have been found in Daya Bay from spring to summer, including high values of DO, nitrate and silicate. Size structures of phytoplankton and its primary production do not change very much from spring to summer, with micro-phytoplankton dominating and contributing about 50% of the whole. In Daya Bay, phytoplankton is limited by nitrogen in spring, and by phosphate in summer. Artificial impacts are evident from high temperature effluent from nuclear power stations, aquaculture and sewage. During the investigation, a red tide occurred in Aotou Bay, with a maximum Chl a of 103.23 mgm(-3) at surface and primary production of 2721.9 mg Cm(-2) d(-1) in the red tide center. Raised water temperature and nutrient supply from land-sources help to stimulate annual red tides.

Biomass↗

[The prevalence of and risk factors for osteoarthrosis in workers in tire manufacture].

The data of epidemiological studies of rheumatic diseases, carried out at the Yaroslavl tire factory among 2508 workers are provided. Overall 845 subjects afflicted with different rheumatic diseases were identified. The prevalence of osteoarthrosis of the peripheral joints was 12.68 +/- 0.66%. The main industrial risk factors of osteoarthrosis were distinguished: occupational hazard (physical overloads), work record in the main specialty over 5 years, functional and static-dynamic loads of the bones and joints, elevated temperature and air humidity in industrial premises. As to the other factors, age, defects of the skeleton, hereditary load, foci of chronic infection, primary education, female sex, and the character of feeding turned out significant for the development of osteoarthrosis. The authors have worked out the tables of risk for osteoarthrosis of the peripheral joints, the use of which allows predicting the morbidity of every worker and distinguishing risk groups with a purpose of carrying out early treatment and prophylactic measures.

Age Factors↗

Factors associated with glycemia and microvascular complications among James Bay Cree Indian diabetics of Quebec.

We conducted a chart review of physician diagnosed diabetics to obtain plasma glucose levels (fasting plasma glucose and glycosylated hemoglobin) over a retrospective 30 month time span and data on the presence or absence of current renal or ophthalmic microvascular complications. Multiple logistic regression was used to determine factors associated with the presence of microvascular complications. Poor glycemic control reflected by a need of insulin therapy (odds ratio (OR) = 2.7, confidence internal (CI): 1.1, 6.7), increased serum triglyceride levels (OR = 4.5, CI: 2.0, 9.9) and duration of illness of more than five years (OR = 3.0, CI: 1.2, 7.8) were found to be associated with the presence of microangiopathies. Process of care and temporary reversion to traditional lifestyle and diet did not influence glycemic control. Our results points towards a need for an increased awareness of lipid disorders in diabetic patients and a better understanding of how social and psychological factors are related to metabolic outcomes.

Adult↗

Safety, tolerability, pharmacodynamics, and pharmacokinetics of rivaroxaban--an oral, direct factor Xa inhibitor--are not affected by aspirin.

Rivaroxaban (BAY 59-7939) is an oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. This was a randomized, 2-way crossover study in healthy male subjects, with an aspirin run-in period, to examine whether aspirin influences the safety, tolerability, pharmacodynamics, and pharmacokinetics of rivaroxaban. All treatments were well tolerated; drug-related adverse events were mild and transient. Aspirin did not alter the effects of rivaroxaban on Factor Xa activity or clotting tests. Platelet aggregation and bleeding time were not affected by rivaroxaban, and rivaroxaban did not influence the effects of aspirin on these parameters to a clinically relevant extent. Aspirin did not affect the pharmacokinetics of rivaroxaban, including the fraction unbound. This study suggests that there is no clinically relevant interaction between rivaroxaban and aspirin and that the 2 drugs could be administered concomitantly at the doses used in this study.

Administration, Oral↗

Generalized common spatial factor model.

There are often two types of correlations in multivariate spatial data: correlations between variables measured at the same locations, and correlations of each variable across the locations. We hypothesize that these two types of correlations are caused by a common spatially correlated underlying factor. Under this hypothesis, we propose a generalized common spatial factor model. The parameters are estimated using the Bayesian method and a Markov chain Monte Carlo computing technique. Our main goals are to determine which observed variables share a common underlying spatial factor and also to predict the common spatial factor. The model is applied to county-level cancer mortality data in Minnesota to find whether there exists a common spatial factor underlying the cancer mortality throughout the state.

Bayes Theorem↗

Calcium channel antagonist properties of Bay K 8644 in single guinea pig ventricular cells.

The effects of Bay K 8644 on the high-threshold calcium channel was investigated by means of the whole-cell patch-clamp technique in single guinea pig ventricular myocytes. The goal of the experiments was to characterize the inhibitory effects of Bay K 8644 on the calcium channel, and identify the factors that influence the inhibition. Bay K 8644 was found to have strong calcium channel antagonist properties, which were both dose- and voltage-dependent. Channel block by Bay K 8644 had both a tonic and a use-dependent component. The stimulatory effect of the drug was found to have little obvious dependence on the holding potential. The accumulation of use-dependent block during trains of pulses was facilitated by faster rates of stimulation, longer pulse durations, and more positive holding potentials. Application of the drug induced the appearance of a second, slow component of calcium channel recovery. Both the time-constant and relative proportion of the slow component of recovery were found to be voltage-dependent. Bay K 8644 was also found to cause a hyperpolarizing shift of the inactivation curve for the calcium current, suggesting that it has strong interactions with the inactivated state of the calcium channel. Thus, Bay K 8644 has, along with its stimulatory effects, inhibitory effects that strongly resemble those of typical calcium channel antagonists.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Incomplete primary excision of cutaneous basal and squamous cell carcinomas in the Bay of Plenty.

AIM: To investigate factors associated with pathologically reported incomplete primary excision of squamous and basal cell carcinomas. METHODS: All Medlab Bay of Plenty histology reports were obtained for all primarily excised cutaneous basal and squamous cell carcinomas of the skin for the Tauranga and Western Bay of Plenty regions covering the period 1 January through 30 June 2001. Data were analysed according to surgical training, site of lesion, pathology, and location of positive margin involvement. RESULTS: 1833 non-melanoma skin cancer excisions occurred during the 6-month study-including 1126 basal cell carcinomas, 705 squamous cell carcinomas, and 2 basosquamous carcinomas. 257 (14%) were reported as incompletely excised. There was no difference in rates of positive margin involvement for gender or histology. Proportionately, excisions from the nose and ear revealed the highest incomplete excision rates. General practitioners excised 1003 lesions, with a 16% incomplete excision rate. Consultant surgeons excised 695 lesions, with a 12% incomplete excision rate. Surgical registrars excised 123 lesions, incompletely excising 8%. These data are statistically significant (p <0.01). Tumour was most often found at lateral (rather than deep) margins. CONCLUSION: The incidence of non-melanoma skin cancer is known to be very high in the Bay of Plenty. Pathologically reported incomplete excision rates are nevertheless comparable with other studies. Of all skin cancers, those on the head and neck are most commonly associated with incomplete excision. Trained surgeons have significantly higher complete excision rates.

Aged↗

[Study of the biopsied nephrotic syndrome for 20 years in the Cadiz Bay Area: histological correspondence, renal prognosis and clinical prognostic factors].

AIMS: To analyse the histological correspondence, the renal survival and the clinical prognostic factors in the nephrotic syndrome for more than 20 years in our environment as well as the influence of the nephrotic proteinuria in the renal survival in the different histological particular types of glomerulonephritis. PATIENTS AND METHODS: Among the 542 primary and secondary glomerulonephritis diagnosed by kidney biopsy for two decades in the Cadiz Bay Area, we selected 242 patients whose clinical presentation and the biopsy indication was the nephrotic syndrome. Statistics methods: means +/- typical deviation, percentiles, percentages, Kaplan-Meier curves, long-rank test, student's t-test, chi-square analysis and Cox proportional hazards model test. RESULTS: 242 patients with nephrotic syndrome (44.66% out of the total of glomerulonephritis), average age of 39.15 +/- 18 years old. Average proteinuria 6.75 +/- 4.53 g/day. ETIOLOGY: membranous nephropathy (33.85%), lupus nephritis (14.46%), minimal change disease (11.57%), focal segmental glomerulosclerosis (10.33%), renal amyloidosis (9.95%). 33%, 45%, 63% and 72% of the patients with nephrotic syndrome developed to the End-stage Renal Disease and starting point of dialysis in 5, 10, 15 and 20 years respectively. After the multivariate model, the age older than 60 years old, the high levels of proteinuria and the coexistence with hypertension or renal failure, in the moment of diagnosis, showed to be independents clinical prognostic factors. The nephrotic proteinuria had a negative influence in the prognosis in the different histological types, especially in the IgA nephropathy and the lupus nephritis. CONCLUSIONS: The nephrotic syndrome is the main indication of the renal biopsy in our environment. In general, as an independent group, its development is slowly progressive to the End-stage Renal Disease, having the possibility of being also conditioned by certain clinical factors present in the moment of the biopsy. The presence of nephrotic proteinuria is also a negative factor in the progression in many of the glomerulonephritis.

Adult↗

Genetic ancestry and risk factors for breast cancer among Latinas in the San Francisco Bay Area.

BACKGROUND: Genetic association studies using case-control designs are susceptible to false-positive and false-negative results if there are differences in genetic ancestry between cases and controls. We measured genetic ancestry among Latinas in a population-based case-control study of breast cancer and tested the association between ancestry and known breast cancer risk factors. We reasoned that if genetic ancestry is associated with known breast cancer risk factors, then the results of genetic association studies would be confounded. METHODS: We used 44 ancestry informative markers to estimate individuals' genetic ancestry in 563 Latina participants. To test whether ancestry is a predictor of hormone therapy use, parity, and body mass index (BMI), we used multivariate logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (95% CI) associated with a 25% increase in Indigenous American ancestry, adjusting for age, education, and the participant's and grandparents' place of birth. RESULTS: Hormone therapy use was significantly less common among women with higher Indigenous American ancestry (OR, 0.78; 95% CI, 0.63-0.96). Higher Indigenous American ancestry was also significantly associated with overweight (BMI, 25-29.9 versus <25) and obesity (BMI, > or =30 versus <25), but only among foreign-born Latina women (OR, 3.44; 95% CI, 1.97-5.99 and OR, 1.95; 95% CI, 1.24-3.06, respectively). CONCLUSION: Some breast cancer risk factors are associated with genetic ancestry among Latinas in the San Francisco Bay Area. Therefore, case-control genetic association studies for breast cancer should directly measure genetic ancestry to avoid potential confounding.

Adult↗

A review of factors influencing measurements of decadal variations in metal contamination in San Francisco Bay, California.

This review summarizes some of the principal results of systematic measurements of trace metal concentrations throughout San Francisco Bay that began in 1989, and that have yielded insights on the factors controlling temporal and spatial variations of those concentrations on seasonal to decadal time scales. Pronounced seasonal variation in some metal concentrations is associated with gradients in the system's hydrology and the diagenetic remobilization of metals from benthic sediments. Additional temporal variation is associated with interannual differences in hydrologic flushing (e.g., ENSO cycles) and episodic storm events. While intra- and inter-annual variabilities complicate assessments of long-term variations in metal concentrations, recent analyses using stable lead isotopic composition distributions and time-series models have deconvoluted decadal changes in lead and silver concentrations in the estuary. Decadal variations in concentrations of other contaminant metals (e.g., mercury) are now being characterized, as well as projections of future concentrations of other metals of concern (e.g., copper). These historic assessments and projections of trace metal variations attest to the importance of long-term, systematic monitoring programs to quantify past and future impacts on water quality in San Francisco Bay and other complex estuarine systems.

Copper↗

Estimating the distribution of worm burden and egg excretion of Schistosoma japonicum by risk group in Sichuan Province, China.

During autumn 2000 an extensive cross-sectional survey of the prevalence of Schistosomiasis japonicum was conducted among about 4000 villagers within 20 villages in the Anning River Valley located in the southwestern Sichuan Province. Two procedures were used to assess infection status, the Kato-Katz thick smear procedure and a miracidia hatch test. Whereas the Kato-Katz procedure provides information on both prevalence and intensity, the hatch test provides only prevalence data, albeit on a much larger volume of stool. In addition, we performed Kato-Katz smears for 15 consecutive samples on a subset of 15 individuals. The proportion of both hatch-test and Kato-Katz positive individuals in the larger cross-sectional survey was 25%. The goal of the study was to estimate both the egg and worm distributions among risk groups using both the hatch and Kato-Katz tests from the cross-sectional data and the repeated Kato-Katz smears from the longitudinal data sets. As a prelude to parameter estimation, individuals were classified into risk groups by natural village and occupation; the proportion of Kato-Katz positive subjects among the risk groups varied from 10% to 60%. We used the statistical model of de Vlas et al. (1992) and Bayesian techniques to derive both estimates of and inference about the worm and egg distribution parameters. The parameter estimates imply (1) similar eggs per gram stool (e.p.g.) per worm pair compared with earlier estimates, (2) a range of worm burdens among the risk groups and (3) estimates of risk heterogeneity within groups is sensitive to prior information on the within-person variability in egg excretion.

Age Factors↗

Predicting coronary heart disease mortality--assessing uncertainties in population forecasts and death probabilities by using Bayesian inference.

BACKGROUND: Predictions concerning people and their health are influenced by many factors and have many sources of uncertainty. Even so predictions can give useful guidelines for health care planning. We present a Bayesian model based on past observations and prior knowledge to predict coronary heart disease (CHD) mortality in selected areas of Finland until the year 2030. METHODS: CHD mortality data are based on official statistics. The study area consists of one western and two eastern parts of Finland. The modelling of the probability of death follows a Bayesian age-period-cohort model. Two models are used, one assuming that the trend from 1970 to 2002 will continue and the other that mortality will stay at the attained level. RESULTS: If the observed trend in CHD mortality were to continue, death probabilities would decrease significantly among men aged 50-69 and women aged 50-59. In the older age groups (men aged 70 and women 60 years or more) the changes were found to be negligible. If the trend continues, the number of CHD deaths will decrease from 2002 to 2030 significantly among men [81% decrease; 95% credible interval (95% CI) 54-96%] and women (90%; 67-100%) aged 50-59. In the age group 60-79 the changes will be smaller and non-significant. In the oldest age group (80-99 years) the predicted increase in the number of deaths will be great, from 284 to 1297 (95% CI 474-2620) in men and from 722 to 1970 (717-4017) in women. CONCLUSIONS: Our predictions emphasize the significance of maintaining the recent decline of CHD mortality among middle-aged adults. Special attention should be paid to CHD mortality among men and women aged 80 and over. Considerable improvements in prevention and treatment are needed to compensate for the effects of ageing of the population.

Age Factors↗

Cortisol rapidly suppresses intracellular calcium and voltage-gated calcium channel activity in prolactin cells of the tilapia (Oreochromis mossambicus).

Cortisol was previously shown to rapidly (10-20 min) reduce the release of prolactin (PRL) from pituitary glands of tilapia (Oreochromis mossambicus). This inhibition of PRL release by cortisol is accompanied by rapid reductions in (45)Ca(2+) and cAMP accumulation. Cortisol's early actions occur through a protein synthesis-independent pathway and are mimicked by a membrane-impermeable analog. The signaling pathway that mediates rapid, nongenomic membrane effects of glucocorticoids is poorly understood. Using the advantageous characteristics of the teleost pituitary gland from which a nearly pure population of PRL cells can be isolated and incubated in defined medium, we examined whether cortisol rapidly reduces intracellular free calcium (Ca(i)(2+)) and suppresses L-type voltage-gated ion channel activity in events that lead to reduced PRL release. Microspectrofluorometry, used in combination with the Ca(2+)-sensitive dye fura 2 revealed that cortisol reversibly reduces basal and hyposmotically induced Ca(i)(2+) within seconds (P < 0.001) in dispersed pituitary cells. Somatostatin, a peptide known to inhibit PRL release through a membrane receptor-coupled mechanism, similarly reduces Ca(i)(2+). Under depolarizing [K(+)], the L-type calcium channel agonist BAY K 8644, a factor known to delay the closing of L-type Ca(2+) channels, stimulates PRL release in a concentration-dependent fashion (P < 0.01). Cortisol (and somatostatin) blocks BAY K 8644-induced PRL release (P < 0.01; 30 min), well within the time course over which its actions occur, independent of protein synthesis and at the level of the plasma membrane. Results indicate that cortisol inhibits tilapia PRL release through rapid reductions in Ca(i)(2+) that likely involve an attenuation of Ca(2+) entry through L-type voltage-gated Ca(2+) channels. These results provide further evidence that glucocorticoids rapidly modulate hormone secretion via a membrane-associated mechanism similar to that observed with the fast effects of peptides and neurotransmitters.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗