Osteopontin and endostatin concentrations in peripheral blood of patients with adrenal tumors undergoing unilateral adrenalectomy.

Peripheral blood osteopontin (OPN) and endostatin (END) levels were studied in 35 patients with adrenal cortex tumors and 10 patients with pheochromocytoma before unilateral adrenalectomy, as well as in 10 healthy subjects (controls). Thirty days after surgery, OPN and END were evaluated again in 16 patients with adrenal cortex tumors and 4 female patients with pheochromocytoma. Before surgery, OPN blood concentrations increased in the group of patients with adrenal cortex carcinomas as compared to controls (p < 0.001) and the group with Conn syndrome (p < 0.05); they did not change after surgery. Before adrenalectomy, OPN blood levels in pheochromocytoma patients were also lower than in Conn syndrome subjects (p < 0.05). After adrenalectomy, the normal concentrations of END decreased only in the group of patients with hormonally inactive cortical adenomas (p < 0.05). We were unable to demonstrate any relationships between removed tumor volumes and OPN or END blood levels.

Resorcylic acid lactone L-783,277 inhibits the growth of the human adrenal cancer cell line H295R in vitro.

The resorcylic acid lactone L-783,277, isolated from a Phoma sp. (ATCC 74403), is a potent and specific inhibitor of MEK (Map kinase kinase) that exerts very interesting pharmacological activities including anti-neoplastic properties. However, the role of this compound in the regulation of endocrine-related cancer cell growth and tumor progression remains unknown. In the present study we have evaluated the effect of L-783,277 on the viability, proliferation and cell cycle of the human adrenocortical carcinoma cell line H295R. L-783,277 inhibited viability (IC50 of 22 microM) and cell proliferation (IC50 of 21 microM) of H295R. At concentrations of 10(-6)-10(-8)M this effect was associated with the accumulation of H295R cells in S-phase, whereas at concentrations of 10(-9)-10(-10)M a prolonged G1-phase and reduced transition into S-phase were observed. Our findings demonstrate for the first time the anti-proliferative action of L-783,277 on the human adrenocortical H295R cell line.

Effect of the growth hormone-releasing hormone [GHRH(1-44)NH2] on IL-6 and IL-8 secretion from human peripheral blood mononuclear cells in vitro.

OBJECTIVE: Bidirectional communication between the neuroendocrine and immune systems is now a subject of an intensive investigation. Growth hormone-releasing hormone (GHRH) is synthesized by the hypothalamus, but is present also in the immune cells. Some recent data indicate also an immunomodulatory role of the neuropeptide. The aim of the study was to examine the influence of GHRH(1-44)NH2 on interleukin-6 and interleukin-8 secretion from human peripheral blood mononuclear cells cultured in vitro. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated by centrifugation using Böyum technique and cultured in a humidified atmosphere of 5 % CO2 and 95 % O2 at 37 degrees C for 24 hours in the presence of lipopolysaccharide (LPS) at the concentration of 2 microg/ml and GHRH(1-44)NH2 (the final neuropeptide concentrations to be tested were 10(-12) to 10(-6) M). ELISA methods were used to measure IL-6 and IL-8 concentrations in the supernatants of cultured cells RESULTS: GHRH(1-44)NH2 influenced IL-6 secretion from cultured cells, but significant inhibition of IL-6 release was observed at 10-6 M (p < 0.001). The negative correlation between the GHRH concentration studied and the IL-6 level in the supernatants was found (r = -0.759; p < 0.001). GHRH had no influence on the secretion of IL-8 from activated PBMC. CONCLUSIONS: Our results demonstrate that GHRH in vitro modulates IL-6 secretion from the human peripheral blood mononuclear cells, without any significant effect on IL-8 secretion.

P53 concentration and soluble FasL (sFasL) serum level as indicators of apoptosis in patients with benign and malignant thyroid tumors.

During embryonal development and morphogenesis, apoptosis may be induced by two pathways. The first is an external protein signal originating from other cell--also named as "death signal". The another one is a specific cell reaction to external stress factors. Plasma concentration of proteins regulating both apoptosis pathways may be useful in early diagnosis and staging of thyroid tumors. The aim of the study was to evaluate p53 and sFasL plasma concentration in patients with benign and malignant thyroid tumors. The study population was composed of 33 patients with thyroid carcinoma and 10 patients with follicular carcinoma (tumor types were verified by fine-needle biopsy). All patients underwent surgical procedures. p53 and sFasL levels were evaluated before surgery. Control group consists of 10 adult healthy volunteers. The results revealed high p53 and sFasL plasma concentration in patients with benign and malignant thyroid tumors. Such results confirm a significant role of p53 and sFasL in apoptosis in thyroid tumors. Expression of both proteins may be an indicator of an increased apoptosis and useful in preoperative diagnosis in thyroid tumors (Tab. 1, Ref. 31).

Effect of growth hormone-releasing hormone (GHRH) and GHRH antagonist (MZ-4-71) on interferon-gamma secretion from human peripheral blood mononuclear cells in vitro.

Numerous reports indicate close interactions between the neuroendocrine and the immune systems. Hypothalamic neuropeptide, growth hormone-releasing hormone (GHRH) stimulates growth hormone (GH) secretion from the anterior pituitary gland, but recently some immunomodulatory properties of this peptide have also been demonstrated. In the present studies we evaluated the effect of human synthetic GHRH(1-44)NH(2) and GHRH antagonist (MZ-4-71) on interferon (IFN)-gamma secretion from human peripheral blood mononuclear cells (PBMC). GHRH(1-44)NH(2) at 10(-10), 10(-8) and 10(-6) M concentrations significantly (p < 0.05) increased the IFN-gamma level in supernatants of cultured cells, as compared with the controls. GHRH antagonist (MZ-4-71) at 10(-10), 10(-8) and 10(-6) M concentrations diminished the IFN-gamma level in supernatants in a dose-dependent manner, but statistically significant differences were observed only at 10(-8) M and 10(-6) M (p < 0.05 vs controls). Our results demonstrate that GHRH and GHRH antagonist MZ-4-71 can modulate IFN-gamma secretion in vitro by human peripheral blood mononuclear cells.

Soluble intracellular adhesion molecules (sICAM-1, sVCAM-1) in peripheral blood of patients with thyroid cancer.

The growth of a neoplasm and its ability to form metastases is a multistep process dependent on angiogenesis and immunological reactions of the organism. In this process adhesive factors are also involved. The aim of this work was estimation of the concentration of soluble intercellular adhesion molecules (sICAM-1) and vascular cellular adhesion molecules (sVCAM-1) in the serum of peripheral blood of patients with thyroid cancer before operation. The study comprised 48 patients ( 38 women and 10 men) aged from 18 to 87 years, in whom thin needle aspiration biopsy revealed cancer of the thyroid. Postoperative histopathological examination showed papillary cancer in 35 patients, oxyphilic cancer in 5 patients, anaplastic cancer in 4 and medullary cancer in 4 patients. In those patients, using the immunoenzymatic method ELISA, the concentration of sICAM-1 and sVCAM-1 in the serum of peripheral blood was determined. The control group comprised 26 healthy persons. We found statistically significant increase of sICAM-1 concentration in serum in all forms of cancer, in comparison with the control group. Mean concentrations of sICAM-1 were as follows: in papillary cancer patients 455.23+/-28.66 vs. 299.62+/-11.54 ng/ml, p<0.05; in oxyphilic cancer 455.60+/-95.21 vs. 299.62+/-11.54 ng/ml, p<0.05; in anaplastic cancer 570.00+/-170.89 vs. 299.62+/-11.54 ng/ml, p<0.05; and in medullary cancer 512.00+/-11.46 vs. 299.62+/-11.54 ng/ml, p<0.05. The mean concentration of sVCAM-1 in serum was statistically significantly higher than in the control group only in case of anaplastic cancer (1033.75+/-86.30 vs. 644.58+/-27.30 ng/ml; p<0.05). We evaluated the correlation coefficient between the concentration of sICAM-1 and sVCAM-1 in the serum of patients with thyroid cancer. Positive correlation was observed between the concentration of sICAM-1 and sVCAM-1. The obtained results confirm essential role of the investigated adhesive factors in the process of thyroid cancer growth.

GH-RH antagonist (MZ-4-71) inhibits VEGF secretion and proliferation of murine endothelial cells.

Angiogenesis plays a key role in solid tumor formation, invasiveness and metastasis. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is necessary in the process of neovascularisation. Antagonists of growth hormone-releasing hormone (GH-RH) have been shown to suppress both in vivo and in vitro growth and metastasis of many human cancer cell lines. The mechanisms that mediate the antitumorigenic actions of these antagonists involve direct and indirect pathways, but are not completely elucidated. We have examined the effect of GH-RH antagonist MZ-4-71 on proliferation activity and VEGF release from cultured murine endothelial cells HECa10 in vitro. MZ-4-71 at 10(-8) to 10(-6) M concentrations inhibited the proliferative activity of cultured cells and suppressed the release of VEGF into supernatants of 72 h endothelial cell cultures. To our knowledge this is the first study reporting antiangiogenic properties of GH-RH antagonists.

Matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and angiogenic cytokines in peripheral blood of patients with thyroid cancer.

Stimulation of growth of endothelial cells from preexisting blood vessels, i.e., angiogenesis, is one of the essential elements necessary to create a permissive environment in which a tumor can grow. During angiogenesis, the matrix metalloproteinase (MMP) family of tissue enzymes contributes to normal (embriogenesis or wound repair) and pathologic tissue remodeling (chronic inflammation and tumor genesis). The proposed pathogenic roles of MMPs in cancer are tissue breakdown and remodeling during invasive tumor growth and tumor angiogenesis. Tissue inhibitors of metalloproteinases (TIMPs) form a complex with MMPs, which in turn inhibits active MMPs. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are unique among mediators of angiogenesis with synergistic effect, and both can also be secreted by thyroid cancer cells. The goal of the study was to evaluate the plasma blood concentration of VEGF, bFGF, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1, and TIMP-2 in patients with cancer and in normal subjects. Twenty-two patients with thyroid cancers (papillary cancer, 11; partly papillary and partly follicular cancer, 3; anaplastic cancer, 5; medullary cancer, 3) and 16 healthy subjects (controls) were included in the study. VEGF, bFGF MMPs, and TIMPs were evaluated by enzyme-linked immunosorbent assay (ELISA). In patients with thyroid cancer, normal VEGF concentrations (74.29 +/- 13.38 vs. 84.85 +/- 21.71 pg/mL; p > 0.05) and increased bFGF (29.52 +/- 4.99 vs. 6.05 +/- 1.43 pg/mL; p < 0.001), MMP-2 (605.95 +/- 81.83 vs. 148.75 +/- 43.53 ng/mL; p < 0.001), TIMP-2 (114.19 +/- 6.62 vs. 60.75 +/- 9.18 ng/mL; p < 0.001), as well as lower MMP-1 (0.70 +/- 0.42 vs. 3.87 +/- 0.53; p < 0.001) levels have been noted. Increased plasma levels of MMP-3 and MMP-9 were also found in patients with medullary carcinoma. In conclusion, predominance of MMP-2 over TIMP-2 and TIMP-1 over MMP-1 as well as increased concentration of bFGF in peripheral blood are common features in patients with thyroid cancer.

Circulating angiogenesis inhibitor endostatin and positive endothelial growth regulators in patients with systemic lupus erythematosus.

Serum concentrations of three angiogenic cytokines: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-18 (IL-18) and antiangiogenic factor endostatin in the serum of 52 patients with systemic lupus erythematosus (SLE) and 20 healthy subjects were investigated. The possible association between serum levels of these proteins and SLE activity as well as correlation between the concentrations of angiogenic cytokines and the level of endostatin was also analyzed. VEGF and IL-18 were detectable in all SLE patients and healthy control group. bFGF was measurable in 71.2% of patients with SLE and 65% of healthy persons. Endostatin was detectable in 94.2% of SLE patients and 95% of normal subjects. The serum levels of endostatin and bFGF were not significantly different in SLE and healthy control (P > 0.05). The median concentration of VEGF was higher in active SLE (238.4 pg/ml) than in inactive disease (118.1 pg/ml, P < 0.05) or in control group (133.5 pg/ml, P < 0.04). The median serum level of IL-18 was higher in the SLE patients (595.2 pg/ml) than in the control group (252.7 pg/ml) (P < 0.001). The correlations between the levels of angiogenic cytokines and endostatin with clinical features, laboratory abnormalities and also with the type of treatment were analysed. We found a positive correlation between VEGF serum concentration and SLE activity according to SLAM score (p = 0.275, P < 0.05). The significant positive correlation was also found between IL-18 and endostatin (p = 0.289, P < 0.04). In contrast, the correlation between bFGF and endostatin was significantly negative (p = - 0.299, P < 0.04). In conclusion, serum levels of the angiogenic and antiangiogenic factors may play an important role in SLE pathogenesis.

Angiogenesis of endocrine gland tumours--new molecular targets in diagnostics and therapy.

Angiogenesis is one of the key stages in the development of neoplastic tumours, in which a small group of mutated cells transforms into a large malignant tumour metastasising to the neighbouring tissues and organs. The studies on the significance of neoangiogenesis in the progression of endocrine gland neoplasms have recently become one of the most rapidly evolving branches of molecular endocrinology. The induction of angiogenesis has been demonstrated to result from the imbalance between positive and negative factors which control this process. Our paper presents the results of current studies on the role of factors such as molecular markers of angiogenesis (e.g. vascular endothelial growth factor and basic fibroblast growth factor), metalloproteinases (which regulate the decomposition of the extracellular matrix) and their inhibitors, and adhesive molecules (e.g. soluble vascular cellular adhesion molecule-1 and soluble intracellular adhesion molecule-1) in the pathogenesis and diagnostics of endocrine gland tumours in humans. Also, we discuss new therapeutic strategies for inhibiting the growth of neoplasms by blocking the formation of blood vessels using angiogenesis antagonists, which inhibit various stages of angiogenesis. More and more data are being accumulated suggesting that these preparations could, in the near future, be used in the pharmacotherapy of some endocrine gland neoplasms.

Serum levels of angiogenic cytokines in systemic lupus erythematosus and their correlation with disease activity.

We investigated the serum concentration of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) using an enzyme-linked immunosorbent assay (ELISA) in a group of 60 patients with systemic lupus erythematosus (SLE), and 20 healthy controls. We also examined the possible association between the serum concentrations of these factors and certain clinical, laboratory parameters and SLE activity. HGF, VEGF and TGF-beta1 were detectable in all patients with SLE, and in all normal individuals. bFGF was measurable in 70% of the patients with SLE and in 65% of the healthy controls. The HGF level was higher in active SLE (median 1,019.5pg/ml) than in inactive SLE (median 787.8 pg/ml) (p < 0.005) or in the control group (median 847.0 pg/ml) (p < 0.009). The level of VEGF in active SLE was also higher (203.5 pg/ml) than in inactive disease (116.1 pg/ml) (p < 0.05) or in healthy persons (133.5 pg/ml) (p < 0.04). The levels of bFGF and TGF-beta1 were similar for both the active and inactive SLE, and the control group (p > 0.05). We found a significant, positive correlation between the levels of HGF and bFGF (r = 0.268, p < 0.04), HGF and TGF-beta1 (r = 0.365, p < 0.005) and HGF and VEGF (r = 0.327, p < 0.02) as well as VEGF and TGF-beta1 (r = 0.543, p < 0.001). We found a positive correlation between VEGF serum levels and platelet counts (r = 0.272, p < 0.04), and the TGF-beta1 concentration and platelet count (r = 0.313; p < 0.02). There was also a positive correlation between HGF serum concentration and the SLE activity score (r = 0.435, p < 0.001), as well as between the level of VEGF and SLE activity (r = 0.252, p = 0.05). In conclusion, serum levels of the angiogenic factors HGF and VEGF may be relevant in SLE pathogenesis. Their concentrations seem to be markers of SLE activity.

Evaluation of MMP-1, MMP-8, MMP-9 serum levels in patients with adrenal tumors prior to and after surgery.

The aim of the study is to evaluate MMP-1, MMP-8 and MMP-9 serum levels in patients with adrenal tumors prior to and after surgery. Metalloproteinase-1 (MMP-1), MMP-8 and MMP-9 serum levels were evaluated in 43 patients operated on at our clinic between 1997-1999. Forty-one (95.3%) patients underwent adrenalectomy. Two (4.7%) patients were disqualified from surgery due to infiltration of adjacent tissues. MMP-1, MMP-8 and MMP-9 serum levels were determined at the admission and in case of surgery again one month after the operation. ELISA assay (K&D) was applied. Tumor type was determined on the basis of clinical, hormonal and histopathological examination. The correlation between MMP levels and tumor sizes was also evaluated. Patients were divided into 6 groups. Group I included 11 patients with adrenocortical carcinoma (4 with Cushing's syndrome and 7 with incidentalomas); group II--6 patients with benign hormonally active adrenocortical adenoma (4 with Cushing's syndrome and 2 with Conn's syndrome); group III--patients with benign, hormonally inactive adenocortical adenoma; group IV--6 patients with benign, hormonally active phaeochromocytoma; group V--4 patients with hormonally inactive phaeochromocytoma; group VI--5 patients with hormonally inactive adrenal tumors of extraglandular origin (2 myolipomas, 2 fibrolipomas, 1 hammartoma). The control group comprised 10 healthy individuals. Increased MMP-8 and MMP-9 levels were noted in patients with benign and malignant adrenal tumors. No increase of MMP levels was found in patients with tumors of extraglandular origin. The increased MMP-8 and MMP-9 levels occurred most frequently in patients with adrenocortical and hormonally active adrenomedullar cancer, and most rarely in patients with hormonally active adrenocortical tumors. MMP-8 and MMP-9 serum levels did not significantly differ between patients with adrenocortical incidentaloma cancers and in patients with benign incidentalomas. MMP-8 and MMP-9 levels were not increased in patients with inoperable adrenocortical cancers. Serum MMP-1 levels were not increased in patients with benign and malignant adrenal tumors. After surgery, MMP-8 and MMP-9 levels decreased significantly in patients with adrenocortical cancers, whereas the decrease of these MMPs in patients with benign tumors, although noticeable, was not statistically significant. MMP-8 and MMP-9 levels decreased significantly in all patients with increased preoperative levels, although they remained higher than the maximum normal values only in few patients (in 7 and 2 patients, respectively). No correlation between the levels of evaluated MMPs and tumor sizes were found.

Usefulness of VEGF, MMP-2, MMP-3 and TIMP-2 serum level evaluation in patients with adrenal tumours.

OBJECTIVE: To estimate serum levels of vascular endothelial growth factor (VEGF), metalloproteases MMP-2 (gelatinase A), MMP-3 (stromyelisine 1) and metalloprotease tissue inhibitors (TIMP-2) in patients with various benign and malignant adrenal tumours before and after surgery, as well as to evaluate if there is a correlation between serum levels of these agents and tumour types. METHODS: Serum levels of VEGF, MMP-2, -3 and TIMP-2 were estimated in 43 patients with adrenal tumour at the admission and, in case of surgery, again one month after surgery. The patients were divided into 6 groups according to the type of the tumour (I - patients with adrenal cortex carcinoma, II - with benign hormonally active adrenocortical adenomas, III - with benign, hormonally inactive adenocortical adenomas (incidentaloma), IV - with benign, hormonally active phaeochromocytomas, V - with hormonally quiescent phaeochromocytomas, VI - hormonally inactive adrenal tumours of extraglandular origin. The control group consisted of 10 healthy individuals. RESULTS: There was no correlation between MMP-2 serum levels and tumour types and no significant difference between MMP-2 level before and after surgery. There were no significant differences between TIMP-2 serum levels in patients with adrenal tumours and the control values. Significant increase of serum MMP-3 level was found in patients with cortex cancer and hormonally active benign adrenocortical tumours. The MMP-3 mean serum level was also significantly higher in patients with malignant incidentalomas than in those with benign ones. In all groups of patients with adrenal tumours the means serum VEGF level was significantly higher than in control patients, and it was also significantly higher in patients with malignant incidantalomas than in those with benign ones. After surgery the VEGF level decreased significantly in patients with extraglandular tumours and cortex cancers who had no recurrence. CONCLUSIONS: Since MMP-3 and VEGF serum levels were found significantly higher in patients with malignant adrenal incidentalomas than in those with benign ones, they might be applied as markers of malignancy of incidentalomas. VEGF and MMP-3 levels decreased after tumour resection in all patients with malignant tumors and increased significantly in patients with recurrence. Therefore, they are supposed to be of prognostic value in these patients.

[Pituitary adenoma penetrating the sphenoidal sinus and nasal cavity: a case report]. / Gruczolak przysadki penetrujacy do zatoki klinowej i jamy nosa--opis przypadku.

We describe a case of pituitary adenoma penetrating to the sphenoidal sinus and nasal cavity in a patient with recurrent nasal polyps. Histopathological examination of the removed polyps revealed transitional carcinoma. CT and MRI of the head showed a solid tumour filling the spheniodal sinus and the sella, penetrating to posterior ethmoid cells and superior nasal duct. In hormonal investigations increased concentration of prolactin (PRL) was found. Histopathological examination performed after neurosurgical operation revealed pituitary adenoma, and the diagnosis of pituitary adenoma was established. About 30% of tumour cells gave positive reaction with anti-PRL antibody in the immunocytochemical investigation. The immunocytochemical investigation of the nasal polips was also done--similarly about 30% of cells showed strong positive reaction with anti-PRL antibody. The investigations indicate the presence of pituitary macroadenoma (prolactinoma), manifesting initially as nose tumour. Considering cases of ectopic pituitary adenomas covered with transitional epithelium (for example some nasal tumours and paranasal sinuses tumours) immunocytochemical investigations are recommended in such cases.

Relationship between circulating interleukin-10 (IL-10) with interleukin-6 (IL-6) type cytokines (IL-6, interleukin-11 (IL-11), oncostatin M (OSM)) and soluble interleukin-6 (IL-6) receptor (sIL-6R) in patients with multiple myeloma.

We investigated the serum concentration of the interleukin-10 (IL-10), along with cytokines of interleukin-6 (IL-6) family (IL-6, IL-11 and oncostatin M - OSM), as well as soluble receptor for IL-6 (sIL-6R), in 121 patients with multiple myeloma (MM) and 28 healthy subjects. We studied the interactions between IL-10 and other cytokines, and the receptor. The correlation between IL-10 and some clinical and laboratory parameters associated with the disease activity were also analysed. The IL-10 was detectable in all patients with multiple myeloma and in all controls. The IL-10 concentration was significantly increased in myeloma patients compared with healthy persons (mean - 7.09 and 2.1 pg/ml, respectively) (p = 0.008). The level of IL-10 correlated positively with the advanced stage of disease estimated according to the Salmon and Durie classification (I versus III stage - p = 0.03). Higher values of IL-10 were found in patients with the light chain disease, hypercalcaemia, and correlated with the elevated concentrations of C-reactive protein (CRP). IL-6 was detected in 117 of the 121 patients and in all controls. The concentration of IL-6 was statistically increased in MM patients compared with control group (mean - 16.06 and 4.49 pg/ml, respectively) (p = 0.01). We found a positive correlation between IL-10 and IL-6 serum levels in MM patients. The relationship, expressed as Spearman's rank sum coefficient (rho = 0.249, p = 0.006) was significant. IL-11 was detected in 26 of the 121 MM patients and in 3 of the 28 healthy subjects at the mean concentration of 1.2 and 0.6 pg/ml respectively (p > 0.05). OSM was at detectable levels in 51 of the 121 patients and in only 4 of the 28 controls (mean - 3.84 and 0.1 pg/ml, p = 0. 002). The correlation between IL-10 and IL-11 levels in MM patients was not significant, but there was a strong statistical correlation between IL-10 and OSM concentrations (rho= 0.327, p = 0.0002). The serum concentration of sIL-6R was measurable in all patients and all controls (mean - 66.00 and 39.57 ng/ml respectively), but the difference between these groups was not significant. We found significant, positive correlation between the levels of IL-10 and sIL-6R (rho= 0.233, p = 0.01). In conclusion, we state that the serum concentrations of IL-10, IL-6, OSM and sIL-6R in MM patients may be a useful markers for the evaluation of the disease activity.

Effects of Gn-RH, TRH, and CRF administration on plasma leptin levels in lean and obese women.

Leptin, a hormone which is produced by adipose tissue, has been shown to inhibit food intake, increase energy expenditure and influence the function of hypothalamo-pituitary-gonadal, -thyroid, and -adrenal systems. We have examined the association between leptin concentrations (RIA method) and levels of different hormones using standard Gn-RH, TRH and CRF tests (at 0, 30, 60, and 120 min) in regularly menstruating 10 lean and 10 obese premenopausal women in follicular phase. FSH, LH, estradiol (E2) and progesterone (P) concentrations in Gn-RH test; TSH, PRL, fT3, fT4 in TRH test; ACTH, DHEA-S, cortisol in CRF test were measured by RIA, ELISA or IRMA methods. The obese subjects had thicker four skinfolds, higher fat content in the body, and bigger BMI, compared to the lean females. Gn-RH test: We have noted higher basal leptin values in obese women than in lean subjects, which was stable during the Gn-RH test. In the same blood specimen, basal insulin concentrations did not differ between the tested groups of patients. There were no correlations between E(2), P, or gonadotropins and plasma leptin concentrations between both groups of patients. We have revealed the negative correlation between LH mobilization (maximal incremental values over basal levels; Delta%) and baseline leptin concentrations in all observed subjects. TRH test: In both groups of patients the leptin levels decreased at 120 min of TRH administration. We have noted diminished PRL and TSH mobilisation in obese subjects in comparison to the controls. In all females (n = 20) the correlations between TSH or PRL mobilization and BMI, skinfold thickness and the mass of body fat in kg were negative. In obese subjects only we observed the positive correlations between fT(3)concentrations at 60 and 120 min of the test or Delta% of fT(3)and leptin levels. CRF test: In obese females, we noted higher basal ACTH and cortisol concentrations with decreased mobilization (Delta%) of ACTH or cortisol, as compared to the controls. Basal leptin values were also higher in obese women comparing controls and did not significantly change within 2 h after CRF injection. In all the observed subjects (n = 20), we noted positive correlations between baseline values of leptin and ACTH, as well as negative correlation between basal concentrations of leptin and mobilisation of cortisol. The obtained results show that the hypothalamic neuropeptides may influence leptin secretion in humans.

Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and soluble interleukin-2 receptor (sIL-2R) concentrations in peripheral blood as markers of pituitary tumours.

Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and soluble interleukin-2 receptor (sIL-2R) are important cytokines. They are secreted by normal pituitary glands and those with all types of adenomas and may be involved in pituitary tissue growth. The peripheral blood concentrations of VEGF, bFGF and sIL-2R in nineteen patients (17-70 years) with pituitary tumours and ten healthy subjects (23-34 years) were studied. Hypersecretion of prolactin (five cases), human growth hormone (four cases), and thyroid stimulating hormone (one case) was recorded in some patients, and the remaining subjects were diagnosed as having nonfunctional pituitary tumours. Increased peripheral blood plasma levels of VEGF (310.82 +/- 59.17 pg/ml) compared with controls (40.32 +/- 11.80 pg/ml; p < 0.01), as well as bFGF (87.27 +/- 7.58 pg/ml) versus controls (11.14 +/- 2.43 pg/ml; p < 0.001) were recorded. The levels of sIL-2R did not differ between the pituitary tumour patients (4,490.58 +/- 581.50 pg/ml) and control subjects (3,617.01 +/- 1,397.18 pg/ml; p > 0.05). The concentrations of VEGF and bFGF in the peripheral blood are useful additional markers of the presence of tumours.

Vascular endothelial growth factor and basic fibroblast growth factor evaluation in blood serum of patients with hormonally active and inactive adrenal gland tumours.

The vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels of 36 patients with adrenal gland tumours were analysed. The mean age of patients was 43 years (29-67 years), and there were 25 women (69.4%) and 11 men (31.6%). In 34 patients adrenalectomy was performed and in two cases lesions were considered inoperable. In all cases VEGF and bFGF were measured preoperatively and in all operated patients the level of VEGF was measured at 1 month postoperatively. A statistically significant increase in VEGF levels before surgery in comparison with the controls was recorded in all patients with adrenal tumours. No correlation between the size of a tumour and VEGF levels was observed. The serum level of VEGF decreased in patients after surgical removal of the tumour, no matter which type of tumour, with the exception of a patient showing a recurrence of cortex cancer. A statistically significant decrease was found only in patients operated on for cortex cancers and hormonally active and inactive cortex and medulla inactive benign tumours. The postoperative recurrence of the malignant tumour may be preceded by an increase in plasma VEGF levels. Such correlations were not found with bFGF.