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Biomedical subjects

J Kunert-Radek

Publications and source records attributed to J Kunert-Radek.

At least 19 recordsLinked to original sources
PubMed2005

The effect of selective sst1, sst2, sst5 somatostatin receptors agonists, a somatostatin/dopamine (SST/DA) chimera and bromocriptine on the "clinically non-functioning" pituitary adenomas in vitro.

The aim of the work was to investigate the effects of somatostatin analogs acting selectively on sst1 (BIM-23926), sst2 (BIM-23120) and sst5 (BIM-23206) receptor subtypes on the viability of "clinically non-functioning" pituitary adenomas in vitro. The effects of native SST (SST-14), a SST/DA chimera (BIM-23A387) and a D(2)-dopamine receptor agonist bromocriptine (BC) were also examined. The study was performed on 10 surgically removed pituitary macroadenomas, diagnosed before surgery as "non-functioning". A part of each tumor was mechanically dispersed and digested with collagenase to isolate the tumoral cells. Another part of each tumor was fixed, embedded in paraffin and immunostained to reveal the pituitary hormones and SST receptor subtypes (sst1, sst2A, sst2B, sst3, sst4, sst5). The tumoral cell suspensions were incubated for 24 h with the substances mentioned above. The quantity of viable cells was estimated using the EZ4U system. The results were compared with the immunohistochemical evaluation of the hormonal profile of adenoma and the sst receptor subtype immunoreactivities present. The findings indicate that selective sst1, sst2 and sst5 receptors agonists, SST/DA chimera and D(2)-dopamine receptor agonist bromocriptine affect the viability of some, but not all, "clinically non-functioning" pituitary adenomas in vitro. The most effective was bromocriptine. The investigated somatostatin analogs including SST/DA chimera exerted roughly similar inhibitory effects. Further studies are needed to fully evaluate the potential usefulness of these compounds in the pharmacological treatment of "non-functioning" pituitary tumors.

Adenoma↗
PubMed2001

Anti-tumoral action of octreotide and bromocriptine on the experimental rat prolactinoma: anti-proliferative and pro-apoptotic effects.

OBJECTIVES: The purpose of the study was to compare the effects of bromocriptine (BC) - D-2 receptor agonist and octreotide (OCT) - somatostatin analog on the tumor weight, prolactin (PRL) secretion, cell proliferation and apoptosis in the diethylstilboestrol (DES)-induced rat prolactinoma. MATERIAL AND METHODS: Male four-week Fisher 344 rats were used in the experiment. The animals were implanted subcutaneously (s.c.) with capsules containing DES. Six weeks after the implantation the rats were given OCT (2 x 25 microg/animal/24 h s.c.) or BC (3 mg/kg b.w./24 h s.c.) for 10 days. The incorporation of bromodeoxyuridine (BrDU) into the tumor cell nuclei was used as an index of cell proliferation (labeling index - LI). The labeling of nuclear DNA fragmentation according to the TUNEL method was considered as an index of apoptosis (AI). PRL was measured by radioimmunoassay (RIA). RESULTS: It has been found that OCT and BC significantly decreased the tumor weight and LI of tumor cells to the same extent. Both OCT and BC suppressed the PRL levels, but the inhibitory effect of BC was stronger than that of OCT. BC and OCT significantly enhanced the number of apoptotic cells in the tumor, but the pro-apoptotic effect of BC was more pronounced. The joint treatment exerted additive effects on tumor mass reduction, PRL secretion and cell proliferation, but OCT attenuated the pro-apoptotic effect of BC. CONCLUSIONS: Summing up, both OCT and BC inhibit PRL secretion and cell proliferation. The anti-tumoral action of BC, and to some extent the action of OCT, is also connected with induction of apoptosis.

Animals↗
PubMed2000

Effect of somatostatin and octreotide on proliferation and vascular endothelial growth factor secretion from murine endothelial cell line (HECa10) culture.

Angiogenesis, development of new blood vessels, is required for normal tissue repair and also for tumor cell proliferation, extracellular matrix invasion, and hematogenous metastases. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that has been shown to play a key role in neovascularization. Inhibition of angiogenesis in vitro and in vivo was documented by administration of native neuropeptide somatostatin and its analog octreotide. We have studied the effect of somatostatin-14 (SRIF) and ocreotide (sandostatin) on proliferation activity and VEGF release from cultured murine endothelial cells HECa10 in vitro. SRIF in concentrations from 10(-9) to 10(-5) M and ocreotide in concentrations from 10(-9) to 10(-5) M diminished the proliferative activity of cultured cells vs controls. SRIF and ocreotide in concentrations from 10(-14) to 10(-6) M did not change the release of VEGF into supernatants of 24 or 72 h endothelial cell cultures. Although we showed the antiproliferative effect of SRIF and ocreotide on mouse endothelial cells, we were unable to demonstrate the inhibitory effect of tested peptides on VEGF secretion in vitro.

Animals↗
PubMed1998

Differential effects of somatostatin and its analog on protein tyrosine kinases activity in the rat pituitary and the murine colonic tumors.

The effects of the native somatostatin-14 (SST-14) and of its analog octreotide (OCT) on the activity of protein tyrosine kinases (PTK) in the normal rat anterior pituitary gland, diethylstilbestrol (DES)-induced rat pituitary tumor and murine colonic cancer Colon 38 were studied in vitro. PTK activity was estimated in tissue homogenates using gamma-[32P]ATP and poly (Glu80, Tyr20) as a substrate. It was found that both SST-14 and OCT suppressed the PTK activity in all examined tissues. The suppressive effect was more pronounced in DES-induced pituitary tumor than in normal anterior pituitary gland, and in the former, OCT was more effective than SST-14. In contrast, SST-14 stronger suppressed PTK activity in colonic cancer than OCT. We hypothesize that SST-14 acts on PTK activity in colonic cancer mainly via SSTR-1 subtype of somatostatin receptors.

Animals↗
PubMed1997

Angiotensin IV stimulates the proliferation of rat anterior pituitary cells in vitro.

The effects of angiotensins II (A II) and IV (A IV) and of A II receptor antagonists losartan (Los) and PD 123319 on [3H]-thymidine incorporation into DNA of the rat anterior pituitary cells in vitro have been studied. The anterior pituitary cells were isolated from the pituitaries of male rats implanted chronically by diethylstilboestrol (DES). It has been found that A IV, like A II, stimulated the tritiated thymidine incorporation into pituitary cells. The effect has not been blocked by antagonists of AT1 and AT2 receptors, Los and PD 123319, respectively.

Angiotensin II↗
PubMed1997

The effect of somatostatin analog octreotide on diethylstilbestrol-induced prolactin secretion, cell proliferation and vascular changes in the rat anterior pituitary gland.

The effects of diethylstilbestrol (DES) and of long-acting somatostatin analog, octreotide (SMS) on the rat anterior pituitary microvasculature have been studied by means of computer-assisted image analysis. Additionally, the effects of DES and SMS on prolactin secretion and anterior pituitary cell proliferation have been studied, as well. The vascularization was visualized using Selye's method modified by Poely et al. (1964). The prolactin serum levels were estimated by radio-immunoassay. The proliferation indices were assessed using bromodeoxyuridine incorporation assay. As expected, it was found that DES sharply increased serum prolactin levels and enhanced cell proliferation in the anterior pituitary gland. DES also induced changes in parameters of vascularization. Simultaneous treatment of rats with SMS inhibited the DES-induced elevation of prolactin levels and pituitary cell proliferation. It also suppressed some but not all DES-induced changes in the anterior pituitary vascularization. These data suggest that the angio-inhibitory activity of SMS might be involved in its anti-tumor action on pituitary adenomas, but not as a sole or principal mechanism.

Animals↗
PubMed1997

Differential effects of somatostatin analogues on proliferation of murine colonic cancer cells in vitro.

The effects of somatostatin analogues octreotide (SMS 201-995), ASS-51 and ASS-52 on [3H]-thymidine incorporation into DNA of the murine colon 38 cancer cells in vitro were investigated. It was found that SMS 201-995 and ASS-51 inhibited the tritiated thymidine incorporation in a dose-dependent manner. In contrast, analogue ASS-52 in spite of a very similar structure to ASS-51, which differed from the latter only by one CH2OH group, was devoid of remarkable antiproliferative activity. These results indicate that slight modification of the molecule of somatostatin analogues may deeply influence their antiproliferative activity.

Amino Acid Sequence↗
PubMed1996

Effects of TRH, prolactin and TSH on cell proliferation in the intermediate lobe of the rat pituitary gland.

The effect of TRH on cell proliferation in the anterior lobe of the pituitary is well known and documented. On the other hand, there are no data on the effects of TRH on the intermediate lobe of the pituitary gland. The aim of this study was to investigate the effect of TRH and its analogues (pGlu-HIs-Gly, pGlu-His-Gly-NH2) on cell proliferation in the intermediate pituitary lobe. The bromodeoxyuridine technique was used to detect the proliferating cells. It was found that TRH stimulated cell proliferation 24 h after a single injection at a dose of 100 micrograms/kg body weight. The TRH analogues did not exert any significant stimulatory effect either 12 h or 24 h after the injection. The second experiment was carried out to distinguish the probable mechanism of the action of TRH. The effects of TSH and prolactin (PRL) on intermediate lobe cell proliferation were examined. It was found that both PRL and TSH exerted a significant stimulatory effect 24 h after a single s.c. injection of PRL at a dose of 150 IU/kg body weight or TSH at a dose 20 IU/kg body weight. It therefore appears that the stimulatory effect of TRH on intermediate pituitary lobe cell proliferation is mediated by PRL and TSH.

Animals↗
PubMed1996

Inhibitory effects of fumagillin and its analogue TNP-470 on the function, morphology and angiogenesis of an oestrogen-induced prolactinoma in Fischer 344 rats.

The process of angiogenesis occurs in many physiological states, but it is also essential for the growth of solid tumours and metastasis formation. An abnormal arterial vascularization has been shown in prolactin-secreting pituitary adenomas induced by prolonged treatment with oestrogens in Fischer 344 (F344) rats. It is thought that anti-angiogenic agents might be useful in therapy for these tumours. Fumagillin and its analogue TNP-470 are known to inhibit endothelial cell proliferation selectively, but their effect on lactotroph cell secretory function and prolactinoma formation has not yet been described. The aim of the present study was to examine the effects of fumagillin and TNP-470 on prolactin secretion, and morphological and vascular changes within the anterior pituitary in long-term oestrogen-treated male F344 rats in vivo and in vitro. As expected, 7 weeks after s.c. implantation of Silastic tubes containing 10 mg diethyl-stilboestrol (DES), a very high rise in serum prolactin levels was found. Both angiogenesis inhibitors injected s.c. at doses of 10 mg/kg body weight for 24 days attenuated the stimulatory effect of DES on prolactin production and release. They also diminished prolactin cell density and inhibited cell proliferation expressed as the number of anterior pituitary cells labelled with bromodeoxyuridine (BrdU), but the effect of TNP-470 was minor compared with fumagillin. Both angioinhibitors suppressed neo-vascularization within the anterior pituitary with similar potency but, on the other hand, they did not affect DES-induced increases in prolactin secretion from cultured rat pituitary cells and cell proliferation in vitro. In conclusion, our results provide strong evidence for the anti-tumour and anti-prolactin activity of angiogenesis inhibitors in the experimentally oestrogen-induced pituitary adenoma; this might be mediated indirectly through the inhibition of angiogenesis.

Animals↗
PubMed1996

The effect of angiotensin II receptor antagonists on diethylstilbestrol-induced vascular changes in the rat anterior pituitary gland: a quantitative evaluation.

The effects if diethylstilbestrol (DES) and of angiotensin II (Ang II) receptor antagonists, such as losartan (selective AT1 receptor antagonist) or PD 123319 (selective AT2 receptor antagonist) on the anterior pituitary microvasculature were studied by means of computer-assisted image analysis. The vascularization was visualized using Selye's method modified by Poely et al. (1964). It was found that DES induced a sharp increase in vessel area, mean vessel diameter and perimeter, whereas mean vessel number was reduced. These DES-induced changes were inhibited by simultaneous administration of losartan. On the other hand, PD 123319 was less effective. These findings suggest an involvement of Ang II, acting mainly via AT1 receptors, in the mechanism of estrogen-induced vascular changes in the rat anterior pituitary gland.

Angiotensin II↗
PubMed1994

Stimulatory effect of angiotensin II on the proliferation of mouse spleen lymphocytes in vitro is mediated via both types of angiotensin II receptors.

The influence of different concentrations of angiotensin II (ANG II) and two specific nonpeptide ANG II receptor antagonists losartan (AT1 receptor blocker) and PD 123319 (AT2 receptor blocker) on the spontaneous proliferation of mouse spleen lymphocytes has been estimated in vitro by the [3H]thymidine uptake assay. It was found that ANG II (10(-6)-10(-12)M) significantly enhanced the [3H]thymidine incorporation into DNA of mouse splenocytes with the maximal effect at 10(-10)M. This stimulatory effect of ANG II on the proliferation of mouse spleen lymphocytes was completely blocked when ANG II receptor antagonists losartan (10(-8)M) or PD 123319 (10(-8)M) were added together with ANG II (10(-10)M). Losartan or PD 123319 tested alone were inactive in this experimental conditions. This findings indicate for the first time the stimulatory effect of ANG II on the proliferation of mouse spleen lymphocytes in vitro. This effect seems to be mediated by both types of ANG II receptors.

Angiotensin II↗
PubMed1994

Inhibition of rat pituitary tumor cell proliferation by benzodiazepines in vitro.

The effect of various benzodiazepines (peripheral-type receptor ligands: Ro 5-4864, PK 11135; central-type receptor ligands: clonazepam, Ro 15-1788, Ro 15-4513; mixed type: diazepam) on the proliferation of estrogen-induced rat pituitary prolactin-secreting tumor cells was studied in vitro. [3H]thymidine incorporation into DNA was used as an index of cell proliferation. It was found that tested peripheral- and mixed-type benzodiazepine receptor ligands significantly suppressed the pituitary cell proliferation in a dose-dependent manner (10(-4)-10(-8) M). The inhibitory effect of Ro 5-4864 was reversed by 5 x 10(-3) M calcium chloride. On the other hand, central-type benzodiazepine receptor ligands suppressed tumor cell proliferation only at the highest concentration studied (10(-4) M). Our results indicate that benzodiazepines might exert an antiproliferative action on pituitary tumor cell growth, and that this effect seems to be a calcium-dependent process.

Animals↗
PubMed1994

Interactions between atrial natriuretic factor (ANF) and thyrotropin or somatostatin in their effects on thyroid growth processes; studies in vitro and ex vivo in vitro.

The goal of our present study has been to examine the effects of the atrial natriuretic factor (ANF) on the growth processes in rat thyroid lobes. In the initial in vitro experiment, thyroid lobes were preincubated with rat ANF (Sigma) for 30 min in RPMI 1640 medium with 3H-thymidine (2 microCi/ml), and later on 15% fetal calf serum (FCS), Hepes buffer and the remaining tested substances [TSH 20 mIU/ml, somatostatin (SS) 10(-7)M] were added. Preincubations with ANF were not conducted in the controls and in the group exposed to TSH alone. Incubations of all the examined groups (controls, TSH alone, ANF alone, ANF together with TSH or ANF together with SS) with 3H-thymidine were carried out for 4 hours. We obtained the following results: at none of the examined concentrations (10(-5)M, 10(-7)M, 10(-9)M), did ANF significantly affect the rate of 3H-thymidine incorporation in vitro. Neither did TSH alone nor ANF with TSH jointly significantly influence the process in question. However, we observed increased rates of the 3H-thymidine uptake, following the joint exposure of thyroid lobes to ANF (10(-7)M or 10(-9)M) and SS (10(-7)M), when compared to ANF alone. In the ex vivo in vitro experiment, direct intrathyroidal microinjections of ANF alone or jointly with TSH or SS, were carried out. Twenty four (24) hours after the microinjections, all the animals were sacrificed by decapitation, the thyroid lobes being collected and incubated for 4 hours with 3H-thymidine (2 microCi/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Changes of 3H-thymidine incorporation into DNA and thymidine kinase activity in rat thyroid lobes, following their exposure to neuropeptide Y.

The effects of neuropeptide Y (NPY) on 3H-thymidine incorporation into DNA of rat thyroid lobes in a 4 h incubation, and on the activity of thymidine kinase (TK) in the homogenates of thyroid lobes in vitro, as well as the influence of thyrotropin (TSH), applied alone or together with NPY, were investigated. The effects of NPY were dependent on the concentration used. Neuropeptide Y, in the lowest and the highest concentrations, decreased both the incorporation of 3H-thymidine to DNA and TK activity, and when used in intermediate concentrations NPY did not significantly affect the processes examined. Thyrotropin decreased TK activity and revealed a tendency towards lowering 3H-thymidine uptake, the latter effect being not statistically significant. NPY (10(-10) M) used together with TSH, produced an increase of 3H-thymidine incorporation into DNA, when compared with controls and the TSH-exposed group. Following the joint exposure to NPY and TSH, TK activity declined.

Animals↗
PubMed1994

Melatonin-induced decrease of the size of thyrocyte nuclei in rat thyroids incubated in vitro.

The mean volume, intersection area and perimeter of thyrocyte nuclei in rat thyroid lobes incubated with melatonin (Mel), thyrotropin (TSH) or with both substances together, were investigated. The measurements were carried out using a computer system for karyometric examination. Melatonin in concentrations of 10(-8) M, 10(-10) M and 10(-12) M significantly decreased the mean nuclear volume and intersection area of thyrocytes (p < 0.01); the mean perimeter of thyrocyte nuclei was significantly decreased by melatonin in concentrations of 10(-10) M and 10(-12) M (p < 0.01). TSH (20 mIU/ml), when applied alone, significantly decreased the mean volume, intersection area and perimeter of thyrocyte nuclei (p < 0.01). TSH generally did not counteract the melatonin-induced decrease of thyrocyte nuclei except for 10(-10) M melatonin concentration when TSH increased the mean nuclear perimeter (p < 0.01) and slightly enlarged the mean volume (p < 0.05), compared with Mel alone. The results suggest an inhibitory influence of melatonin on thyroid follicular cell activity, and are in compliance with earlier observations.

Animals↗
PubMed1993

[Effect of melatonin on the function of the pituitary-gonadal axis in food restriction states].

The effects of melatonin (25 micrograms s.c. daily in the late afternoon during ten days) on the ovarian morphometry and the gonadotropin secretion were investigated in food-restricted and fed ad libitum rats. It was found that in food-restricted rats melatonin produced the significant decrease of the surface area of the whole ovary and of zona granulosa. Moreover melatonin treatment of food-restricted rats resulted in significant decrease of the relative areas of graafian follicles and zona granulosa estimated in relation to the whole ovary cross-section surface area. On the other hand melatonin did not produced significant alterations of the morphometric indices of the ovary in fed ad libitum rats. Melatonin administration was found to inhibit the effects of gonadotropin release in food-restricted but not in normally fed rats. These findings suggest that food restriction sensitizes the pituitary ovarian axis to antigonadotropic melatonin action.

Animals↗