Jolanta Kunert-Radek

Evaluation of Interleukins, ACTH, Cortisol and Prolactin Concentrations in the Blood of Patients with Parkinson's Disease

Parkinsons disease (PD) is characterized by a markedly decreased number of nigrostriatal dopaminergic neurons. The pathogenesis of PD is still unknown; among other etiological factors, immunological abnormalities have been suggested. Recently, interleukin-2 (IL-2) has been hypothesized to be an endogenous cytokine that regulates striatal dopaminergic function. We examined the plasma concentrations of IL-1, IL-2, IL-6 and blood levels of ACTH, cortisol and prolactin of 21 patients with PD without any previous treatment. Age- and sex-matched subjects without any neurological or immune disorders were used as controls. Significantly higher serum concentrations of IL-2 in patients with PD were found. Treatment with antiparkinsonian drugs reduced IL-2 levels in these patients. Our results suggested a functional relationship between central dopaminergic and immune systems and a possible involvement of the latter in the pathogenesis of PD.

Effect of somatostatin on the proliferation of mouse spleen lymphocytes in vitro

The effect of somatostatin on the spontaneous proliferation of mouse spleen lymphocytes was investigated in vitro. The rate of 3H-thymidine incorporation was used as an index of lymphocyte proliferation. Somatostatin in a concentration of 10(-7) M enhanced the lymphocyte proliferation and abolished the antiproliferative effect of rat hypothalamic extract. Lower concentrations of somatostatin slightly decreased the lymphocyte DNA synthesis.

Immunomodulatory action of somatostatin

The influence of somatostatin (SST) on spontaneous proliferation and cyclic AMP level in mouse spleen lymphocytes and on inhibition of human leukocyte migration was studied. The rate of [3H]thymidine incorporation was used as an index of proliferation. It was found that lower concentrations of SST/10(-9) and 10(-8)M, inhibited the splenocyte proliferation. In contrast, a higher SST concentration, 10(-7)M, exerted a stimulatory effect. SST in concentrations from 10(-9) to 10(-6)M did not influence cyclic AMP levels in mouse splenocytes; a significant decrease of cyclic AMP was found after the exposure to superactive SST analog RC-102-2H in concentrations 10(-8) and 10(-7)M. SST, 10(-7)M, and RC-102-2H, 10(-7)M, significantly enhanced the migration inhibition of human leukocytes induced by the exposure of leukocytes to cardiac antigen or phytohemagglutinin. The data provide evidence for an immunomodulatory action of SST.

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.

The Effect of Thyrotropin Releasing Hormone on Cell Proliferation in the Anterior Pituitary Gland of Thyroidectomized Rats

In thyroidectomized rats, a single injection of TRH (25 µ g) results in a marked increase in the number of mitoses in the anterior pituitary gland 12 h after injection, followed by a

Angiotensins II and IV stimulate the activity of tyrosine kinases in estrogen-induced rat pituitary tumors.

The effects of angiotensin II (AngII) and its fragment 3-8 (angiotensin IV, AngIV) on tyrosine kinase (TK) activity in estrogen-induced rat pituitary tumor homogenates were studied. It was found that both angiotensin peptides increase the TK activity. AngIV was effective in a lower concentration and its maximal effect was greater as compared to that of AngII. Moreover, the specific inhibitors of aminopeptidase A (EC33) and of aminopeptidase N (PC18) significantly attenuated the stimulatory effect of AngII. Because the action of both aminopeptidases is necessary to convert AngII into AngIV, this finding suggested that the effect of AngII on TK activity is (at least in part) exerted via AngIV.

SSTR1 and SSTR5 subtypes are the dominant forms of somatostatin receptor in neuroendocrine tumors

The effectiveness of the long acting somatostatin analogues like octreotide and lanreotide depends on the expression of specific somatostatin receptors on the target cells. The immunohistochemical method performed on surgically removed tumors searches the expression of receptors at the level of receptor protein and gives us insight into receptors cellular localization. The aim of study was to assess the presence of all the 5 subtypes of SSTR 1-5 (including 2A and 2B SSTR isoforms) in surgically treated human neuroendocrine tumors (NETs) to establish which receptor subtype is the dominant form of somatostatin receptor in particular tumor and thus to be able to predict which somatostatin analog will be effective in NETs treatment. 18 samples of neuroendocrine tumors (surgically excised tumors or biopsies) were immunostained with specific antibodies. Expression of SSTR was scored semiquantitatively. Only strong or moderate immunostaining was considered as positive reaction. The summarized expression pattern of SSTR in the investigated neuroendocrine tumors in our material was: SSTR 1> SSTR 5> SSTR 3> SSTR 2A> SSTR 2B. The receptors were distributed mainly in the area of cells cytoplasm with a few specimens showing only membranous or mixed: membranous--cytoplasmic localization. The observed pattern suggests that apart from octreotide and lanreotide, newly synthesized multiligand analogs such as SOM 230, KE 108 or SSTR 1 and SSTR 5 selective analogs could be effective in NETs treatment.

Melatonin inhibits growth of diethylstilbestrol-induced prolactin-secreting pituitary tumor in vitro: possible involvement of nuclear RZR/ROR receptors

Melatonin exerts a marked antiproliferative action in numerous experimentally‐induced tumors in vivo as well as in both animal and human cell lines in vitro. However, the mechanisms of oncostatic action of melatonin is not clear, and the involvement of both membrane and nuclear receptors are suggested. Therefore, the aim of this study was to investigate effects of melatonin, and both agonist (CGP 52608), and antagonist (CGP 55644) of RZR/ROR nuclear receptors on the growth of diethylstilbestrol‐induced rat prolactin‐secreting pituitary tumor cells in vitro.

Thyroxine Inhibition of the Proliferative Response of the Anterior Pituitary to Thyrotropin Releasing Hormone in vitro

TRH increased cell proliferation in organ-cultured rat adenohypophysis. Thyroxine by itself had no effect on adenohypophysial cell proliferation in vitro but inhibited the mitogenic effect of TRH.

Angiotensin II stimulation of the rat pituitary tumoral cell proliferation in vitro

The effect of angiotensin II (AT II) on proliferation of rat pituitary tumoral cells was investigated in vitro. The tumoral cells were isolated from the prolactin-secreting pituitary tumors induced by stilboestrol implantation. The incorporation of [3H]-thymidine into DNA was used as an index of cell proliferation. It was found that AT II significantly enhanced the [3H]-thymidine incorporation into pituitary tumoral cells in the concentrations of 10(-10) and 10(-8) M. The stimulatory effect disappeared at the concentration of 10(-6) M. The possible involvement of pituitary renin-angiotensin system in pituitary tumorigenesis was discussed.