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Cancer pain is one of the main problem in modern medicine. According European Society for Medical Oncology data, cancer pain prevalence is 64% among patient with terminal stage of disease and in 46% standard pain therapy was ineffective. Radiosurgical hypophysectomy is one of the important and perspective method in cancer pain treatment. This method could be offered patient with chronic disease. According literature review, endocrinology complications were very rare and occurred 10 months after therapy. Value of analgesic effect was 70-90%. In some trials, procedure was effective not only nociceptive, but also in neuropathic pain. More trials require for determination of indications and mechanism of action. The case of successful relief of resistant pain in patient with pancreatic cancer by means of radiosurgical hypophysectomy is described.

The aim of the paper was to investigate effects of Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly peptides which were designed and synthesized on the basis of amino acid study of the hypophyseal anterior and posterior lobe peptides on the thyroid morphology and hormonal activity in mature chicken and old birds. Hypophysectomy was established to produce atrophic changes in the thyroid gland and development of secondary hypothyrosis. Administration of Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly tetrapeptides significantly prevented these impairments by increasing the levels of the thyroid-stimulating hormone (TSH) as well as T3 and T4. Restoration of the thyroid functions and morphology was registered to be greater in one-year-old chicken as compared to five-year-old ones.

Neonatal hypophysectomy in chicken produces enlarged follicles of the thyroid gland, accumulation of colloids, impressed follicular epithelium, increased nucleus-cytoplasm ratio in thyrocytes, atrophied inter-follicular epithelium, depressed immunity, development of hypercoagulation and depressed fibrinolysis. When hypophysectomy is performed in one-year-old birds the impairments developing in thyroid morphology, immunity and hemostasis are less pronounced. Peptides of the anterior (Lys-Glu-Asp-Gly) and posterior (Ala-Glu-Asp-Gly) thyroid lobes injected to hypophysectomized birds prevent atrophic changes of the thyroid gland, normalize immune and hemostatic parameters.

It has been found that chicken hypophysectomized early in the neonatal period develop anemia, cellular and humoral immune deficiency, hypercoagulation and inhibited fibrinolysis by their 45th postnatal day. An analogous operation performed on old birds produces less significant changes in erythrocytes, immunity and hemostasis. Injections of epithalon tetrapeptide (Ala-Glu-Asp-Gly) administered to either hypophysectomized chicken or old birds during a period of 40 days completely eliminate the shifts registered in erythrocytes, immunity and hemostasis, while injections of cortagene (Ala-Glu-Asp-Pro) which is distinguished from epithalon by a different terminal aminoacid (with Gly being replaced by Pro) do not affect the parameters studied.

Neonatal hypophysectomy in chicken, as well as that in old hen has been established to entail in 1,5 months after surgery cellular and humoral immunity disturbances, pronounced hypercoagulation and fibrinolysis depression. Administration of Epitalon (Ala-Glu-Asp-Gly) to a large extent eliminates revealed shifts. This effect appeared to be stronger in neonatally hypophysectomized chicken than in old hens.

It was shown in experiments on white mongrel rats that some components of the diffuse neuroendocrine system are involved in the realization of magnetobiological effects.

In hypophysectomised noninbred [correction of inbred] rats and in male rabbits, a direct influence of stimulation with oxytocin, vasopressin, dopamine of the hypophysis substance's adenocytes enhanced their proliferation as well as the DNA synthesis. The role of hypothalamic nonapeptides as the regulators of cells and tissues homeostasis is discussed.

In 21--23-day-old female Wistar rats with atresia of the ovarian follicles, naloxone administration increased the number of 100-200 mcm follicles with atresia-induced changes, whereas enkephaline prevented the effect. Role of the brain opioid system in the above phenomenon, is discussed.

Immunohistochemistry and histomorphometry were employed to assay thyroid and parathyroid glands in hypophysectomized rats following a10-day tail suspension in head-down position and daily injection of either physiological solution or growth hormone or insulin-like growth factor 1 on the background of physical exercise, i.e. ascent up a 1 m high staircase with a load fastened to the tail. Hypophysectomy was found to cause atrophic/sclerotic changes in the thyroid and parathyroid glands, and dramatically suppress the functional activity of thyrocytes, C-cells (calcitonin producers) and parathyrocytes (parathormone producers). Assumingly, the impairing effect of hypophysectomy on C-cells and parathyrocytes is consequent to the reduced production of thyroid hormones and concomitant moderation of metabolism. The suspension by tail added somewhat to the severity of changes in thyroid and parathyroid glands under the effect of hypophysectomy, whereas the injection of growth hormone or insulin-like growth factor 1 slightly stimulated thyrocytes, C-cells, and parathyrocytes activities; however, it failed to offset the hypophysectomy-provoked developments. Although the activities of thyrocytes, C-cells or parathyrocytes were not affected by physical exercise, there was a mild C-cell proliferation.

Accessory groups (AG) of oxytocin (OT)--and vasopressin (VP)--ergic cells (circular, perifornical, ventro- and dorsolateral groups and periventricularly localized nonapeptidergic cells) were studied morphometrically in intact and hypophysectomized rats. Additionally, the AG of medulla stria thalamus was demonstrated and investigated. The total number of nonapeptidergic cells in the AG is about 600 cells. The AG consist of OT-ergic cells predominantly (58%) except the perifornical group (68%) VP-ergic cells) and ventrolateral group (equal propotion). 7 days after hypophysectomy the size of perikaryon, nucleus and nucleolus of the cells in AG decreased, though, in contrast to the supraoptic and paraventricular hypothalamic centres, no degeneration of cell occured. That is why it is possible to suggest, that axons of the AG cells do not project to the posterior pituitary. The absence of hypertrophy of the AG cells in compensatory function of degenerating cells in the supraoptic and paraventricular nuclei indicates a functional diversity of these nonapeptidergic cells.

Experiments on white rats found that both chronic acidosis and chronic alkalosis cause fasting hyperglycemia and decreases glucose tolerance. In hypophysectomized animals, alkalosis causes similar effects and acidosis leads to hypoglycemia. Acute acidosis stimulates insulin and corticotropin secretions acute alkalosis reduces blood insulin and corticotropin levels and increases glucagon concentration. Chronic acidosis and alkalosis decrease insulin secretion and stimulates corticotropin secretion. Glucagon levels remain increased in chronic alkalosis. It has been concluded that primary cause of diabetogenic action of chronic acidosis is glucocorticoid hyperfunction and exhausting stimulation of B cells with glucose. Alkalosis causes a direct inhibitory action on B cells and activates A cells of Langerhans' islets.

Response of the vasopressin (VP) and oxytocin (OT) cells of hypothalamic post optical nucleus (PON) was studied in male Wistar rats under various experimental conditions. Seven days after hypophysectomy, the majority of both VP- and OT-cells became pyknomorphic which seemed to be the result of transsection of the PON-cell axons and indicated that the PON-cells released neurohormones from the posterior pituitary into the blood. When rats were cooled (2 h at 4 degrees C), the size of nucleoli in VP-cells diminished significantly, but in rats stressed by severe immobilization (20 min) these cells revealed clear signs of activation. In contrast to that, no changes were observed in the OT-cells after these treatments. The functional relation of the PON and thyroid gland is discussed.

Effect of various doses of oxytocin, vasopressin or adrenalin on the thyroid gland activity was studied in hypophysectomized and nonoperated rats 20 minutes after a single injection of the neurohormones. The minimal applied dose of the neurohormones stimulated increasing of their concentration in blood up to level typical for stress reaction. Injection of oxytocin led to no effect at any dose. In nonoperated rats vasopressin stimulated the thyroid gland but did not influence on TSH level in blood. In hypophysectomized rats thyrostimulating effect of vasopressin was also detected need. Adrenalin injection inhibited the thyroid gland function in both nonoperated and hypophysectomized rats. Effect of adrenalin in combination with vasopressin was like the action of adrenalin alone. Thus, it is possible to assume that under stress conditions a high blood level of adrenalin attenuates thyrostimulating effect of vasopressin.

Luliberin's analogue (surfagon) has been established to activate shock-induced aggression of short-sleeping (SS) and long-sleeping (LS) rats in painful stress. The using of the castration and hypophysectomy has proved this effect to result from the direct neurotropic action of peptide. It has been shown, that SS rats differ from LS ones by more expressed reducing of painful aggressive and reference reactions after castration and hypophysectomy as well as by definitive peculiarities of peptidergic effects of surfagon.

Using morphometric technique, it has been shown that single and especially three successive injections of a hypothalamic nonapeptide neurohormone, arginin-vasotocin (5.10(-9) M/kg of body weight) affect functional activity of the thyroid gland in sexually mature male frogs which had been subjected to hypophysectomy 10 or 60 days before neurohormonal treatment. These data presumably confirm a hypothesis about the direct para-adenohypophysial influence of the hypothalamic nonapeptide neurohormone on the peripheral endocrine glands, particularly, the thyroid one.

The localization of an unusual estrogen-binding protein (UEBP) was studied in the rat liver using indirect immunoperoxidase reaction in intact rats and after different hormonal influences. The distribution of the UEBR in normal males displays a form of a gradient with the maximum near the central veins. The gradient is absent in normal females. Castration or hypophysectomy of males, or their injection with estradiol or triiodyronine leads to a decrease in the UEBP concentration, though the gradient character of its distribution is persisting. There is a stable increase in the UEBP concentration in the first two layers of cells adjacent to the central veins in the female rat liver after ovariectomy and especially in combination with androgen injections. The revealed changes in the intensity of immunoperoxidase reaction after different hormonal influences correlate with the UEBP concentration in liver studies performed by the radioligand assay.

The purpose was to determine the effect of a complex of factors of large cell (supraoptic, paraventricular) or small cell (arcuate) hypothalamic nuclei on adenohypophyseal proliferation and cytodifferentiation, manifested in body tissue culture. Experiments were staged on 80 hypophysectomized random bred albino male rats with a body mass of 200-230 g. The evaluation of cell types of adenocytes was performed at stages of implantation every 12h-26 days with the help of light optic, electron microscopic, histoautoradiographic, immunohistochemical and radioimmunoassay methods. Supraoptic and paraventricular nuclei were shown to provide for the stimulation of adenocytic proliferation. The factors of paraventricular nuclei enhanced secretion in somato-, mammo-, thyro- and corticotropocytes and created conditions for their secondary cytodifferentiation.

The possibility of direct androgen determination of high unusual estrogen-binding protein (UEBP) level in female rat hepatocytes to the level typical to the males was studied. The direct effect of androgen (A) on the UEBP content in hepatocytes of ovariectomized female rats was shown by estimation in vivo and on hepatocyte culture. It has been revealed that the permissive action of growth hormone (GH) is necessary for normal expression of direct androgen effect. The latter has been stable after cessation of hormone action. High concentration of GH was found to possess positive regulatory effect on the UEBP in hepatocytes of ovariectomized rats. Effect of GH quickly disappeared after hormone withdrawal and was under negative regulation by physiological concentrations of A. It was concluded that A owing to its direct action together with permissive influence of GH is capable of determining stable expression of male phenotype of the UEBP level in hepatocytes of females.

The role of the pituitary gland was investigated in the regulation of the level of rat liver androgenic receptors (AR) and in the realization of polydifferentiating action of gonadal hormones. The level of AR in the female and male rat liver was shown not to depend directly on the presence of the pituitary gland or STH administration. The pituitary gland is not a mediator in the realization of polydifferentiating action of androgens and estrogens. STH enhances the development of a positive effect of androgens on the level of AR.

The simulation of the hypo- and hyperactivity of the hypophysis-adrenocortical system induced considerable changes in the reactivity of alpha 2-adrenoceptors, as well as in the resistance of the organism to stressful influences. The findings support the assumption that the blockade of alpha 2-adrenoceptors is one of the key features in the adaptive mechanism of the glycocorticoid hormones action.

In CBA mice immunized with the sheep red blood cells (5 x 10(8)), the section of the pituitary stalk prevented the changes in the immune response caused with drugs affecting the activity of GABA-ergic system. Activating effect of the benzodiazepine receptor agonist diazepam, and inhibitory effect of bicucullin on the immune response were not manifest in animals after the lesion of the hypothalamo-pituitary stalk. The mechanism of increasing of the L3T4 T-helpers in bone marrow under the effect of GABA-ergic system activity was also actualized through the hypophysis. The central GABA-ergic mechanisms of the neuroimmunomodulation are discussed.

Using radioimmunoassay it has been detected that both nonoperated and hypophysectomized, lacking endogenous ACTH, frogs injected one or three times with arginine vasotocin (5.10(-9) M/kg b. w.) show a statistically significant increase of plasma corticosterone level as compared with that in control animals and frogs injected with Ringer solution. The level of 11-hydroxycorticosteroids (fluorometric determination) in the interrenal gland decreases significantly only in animals three times injected with arginine vasotocin. It is assumed that arginine vasotocin produces a direct stimulatory effect on corticosteroid-producing cells of the frog interrenal gland.

A significant increase of the content of corticosterone in the blood collected from intravenous cannula or by intracardiac punction has been detected using radioimmunoassay in non-operated and adenohypophysectomized frogs Rana catesbeiana subjected to dehydration in 6.2% mannitol solution during 24 hours. The osmolality of the blood plasma of these animals also increases although less significantly than the growth of plasma corticosterone content. There is a tendency to substantial increase of plasma arginine-vasotocin level prior to the growth of corticosterone level, already after 6 hours of dehydration. Based on the present results and literature data, it is suggested that in adenohypophysectomized frogs lacking endogenous ACTH just the increase of blood arginine-vasotocin level results in a substantial activation of corticosteroid-producing cells of the interrenal gland and in the growth of plasma content of corticosterone.

The procedure designed for the estimation of estrogen receptors (ER) in rat liver cytosol using sodium thiocyanate was shown to be useful for differential quantification of the ER level in liver cytosol of male rats, containing the unusual estrogen-binding protein. The ER concentration in rat liver cytosol was shown to be a sex dependent feature: its content in male rats (55 +/- 4 fmol/mg of protein) was lower (p 0.001) than that in female rats (116 +/- 4 fmol/mg of protein). The differences in the ER content were revealed only after maturation and disappeared after hypophysectomy of adult rats. Gonadectomy of males performed on the 1st postnatal day or in the pre- or postpubertal period resulted in complete "feminization" of the ER content in these animals. Ovariectomy in female rats at all stages of ontogenesis did not influence the ER level in liver cytosol. It was concluded that androgens have no programming, but only a negative regulatory influence on the ER level in rats.

Male Wistar rats were hypophysectomized 1 week before restraint stress. The hypophysectomy caused a decrease of blood vasopressin (30%, P less than 0.05) and a diminution of the thyroid activity (the thyrocyte height lowered to 43%, P less than 0.01). The TSH concentration was about normal and remained constant during the experiment. After 20 min of the restraint stress, the vasopressin concentration reached 178% (P less than 0.01), but the thyroid did not response in rats with the intact hypophysis. In the hypophysectomized rats, the restraint stress caused neither essential changes of the blood vasopressin nor the thyroid function as compared with the hypophysectomized control. An injection of vasopressin (5.0 ng/100 g) or oxytocin (15.0 ng/100 g) resulted in a slight activation of the thyroid in the hypophysectomized rats but significantly stimulated in when combined with the restraint stress; vasopressin injection led to an increase of the thyrocyte height to 152% (P less than 0.01), oxytocin--to 126% (P less than 0.05). Thus, in hypophysectomized rats, vasopressin and oxytocin can influence the thyroid directly. Stressful conditions facilitate the thyroid stimulating effect of these nonapeptide neurohormones.

The rate of 35S-methionine incorporation into the anterior and posterior hypothalamus, tonsil and hippocamp was studied in experiments on intact, adrenalectomized, and hypophysectomized rats as well as in those exposed to ACTH or dexamethasone. A conclusion is drawn that ACTH and glucocorticoids exert a dissimilar and non-equivalent effect on the brain structures responsible for the activity displayed by the hypophyseal-adrenal system.

A simple method for isolating hepatocytes from the liver with the aid of trypsin and their cultivation is described. The functional activity of the primary monolayer culture of hepatocytes was evaluated from the rate of albumin synthesis and secretion. The basal rate of albumin synthesis was fairly high during the first 10 minutes but after 2 hours decreased and reached plateau. On the contrary, the basal rate of albumin secretion rose with time and after 2 hours attained the rate of albumin synthesis. Human growth hormone (500 ng/ml) stimulated albumin output within 3 hours of incubation with hormonal stimulation in the cells from hypophysectomized rats being more pronounced as compared to that seen in hepatocytes from intact animals. A conclusion is made that the hepatocyte culture prepared by the method described can produce a release albumin and retains sensitivity to the hormonal regulator.

The influence of 4-nitro-3-trifluoromethylisobutyranilide (niftolide, flutamide) on the blood plasma testosterone content, the level of the total and specific activity of testicular steroid- delta5-3beta-ol-dehydrogenase was studied in the experiments on male rats in the early (5 days) and late (30 days) periods after hypophysectomy. The operation completely prevents gonadal response to antiandrogen administration. The data obtained indicate that niftolide does not exert direct effect on androgen production in the rat testes.

The work is devoted to a study of the hypophysis control of the adrenal cortex hormone--18-hydroxy-11-deoxycorticosterone (18-HO-DOC) secretion; these investigations were performed on 136 mongrel female rats, weighing 130-140 g. The regulating role of the hypophysis on the 18-HO-DOC secretion was ascertained on the hypophysectomized animals (pseudohypophysectomized animals served as control) and intact rats to which ACTH was administered (physiological saline was injected to control animals). The rate of secretion, specific rate of secretion, and the secretion content in the blood and in the arenal efferent and the peripheral vessels were determined by thin-layer chromatography and competitive protein binding. The data obtained led to the conclusion that both corticosterone and 18-HO-DOC were regulated by the hypophysis. Under the effect of stress there apparently occurred selective regulating action of ACTH on 18-HO-DOC and corticosterone secretion indicating that the expediency of elevation of one or another steroid secretion was determined by the character of stress reaction, the blood adrenocorticotropin and corticosteroid level.

Using ion-filtration chromatography on DEAE-Sephadex A-25, a homogeneous polynucleotide phosphorylase having specific activity of 350--360 u./mg and containing no admixtures of nucleases or phosphatases was obtained. Injection of 32P phosphate to hypophysectomized animals was accompanied by the label incorporation into the enzyme molecule. The data obtained indirectly indicate that the enzyme is activated by phosphorylation and is inactivated by dephosphorylation, both processes being mediated by some factor found in liver cytosol of intact animals.

With a prolonged enteral introduction indole alkaloids vincamine (5--20 mg/kg), vinervine (5 mg/kg) and serotonin (2 mg/kg) significantly lengthen the duration of the sex cycle through extending the estrus cycle (vincamine, vinervine and serotonin) and diestrus (serotonin). Without changing the weight of the uterus the studied alkaloids tend to significantly increase the weight of the ovaries and the number of follicles therein. In test with sexually mature castrated and also sexually immature (both alkaloids) and hypophysectomized (vincamine) animals these alkaloids fail to display any estrogenic action.

After hypophysectomy luteinizing hormone /LH/ did not disappear from rat blood serum within 2 months; but concentration of the hormone decreased 2-fold. Administration of luliberine into the hypophysectomized rats led to approximately 3-fold increase of the LH concentration in blood serum within 20 min. The hormones from blood serum of the hypophysectomized rats, from hypophysis and blood serum of intact rats exhibited similarity in their immunochemical and chromatographic properties. The data obtained suggest the presence of extrahypophyseal sources of LN in rats. By means of radioimmunochemical procedure immunoreactive LH was found in 14 structures of the central nervous-system/brain cortex, hypothalamus, hippocampus, medulla oblongata etc/as well as in some peripheral tissues and glands/heart, liver, pancreas etc/. Chromatographically pure LH from liver tissue of the hypophysectomized rats exhibited the biological activity similar to that to the hypophyseal hormone, which was estimated by stimulation of testosterone biosynthesis in the testicular tissue in vitro.

Content and relative concentration (per 1 mg of protein) of luteinizing hormone (LH) varied in rat hypothalamus depending on the animal sex and age. In hamster hypothalamuses the hormone content correlated with the state of sexual cycle; maximal content of LH was found during estrus. Content of LH in hypothalamus depend also on the effect of light (rhythmic illumination, permanent light or darkness, duration of the light effect). After gonadectomy content of LH was increased in hypothalamus of female rats within 60 days. Simultaneous hypophys- and ovariectomies increased the LH content in hypothalamus already within 14 days after the treatment. Whole-body perfusion of rats did not alter the LH content in hypothalamus. LH was found in the middle and posterior parts of hypothalamus, particularly, in arcuate nucleus, middle eminence and mammillary bodies.

Hypothyreosis or the injection of actinomycin D have been shown to reduce the expression in dedifferentiation changes that take place in the fascicular and reticular zones of the adrenal gland cortex of hypophysectomized rats. The reduced intensity of such a dedifferentiation may occur due to the suppression of m-RNA synthesis, the character of the power resulting in the inhibition of DNA-dependent polymerase (actinomycin D or hypothyreosis) having no real significance.

The reactivity of pancreatic B-cells of the decapitated and encephalectomized rat foetuses was determined by changes of insulin secretion in response to glucose introduction in the incubation medium. Upon removal of hypophysis together with hypothalamus in the intact rat females and females with alloxanic diabetes on the 17.5-18.5 day of prenatal development, their pancreas, unlike that of the control foetuses, remained refractory to glucose on the 21.5 day of development. The removal of hypothalamus only upon encephalectomy of the foetuses of the same age led to a similar effect, thus suggesting possible influence of hypothalamus on the regulation of functional maturation of the pancreatic B-cells in the end of prenatal development. Upon the combined incubation of pancreas fragments of the decapitated rat foetuses with adenohypophyses of the adult rats, the effect of decapitation was cut short and the gland responded by the increase of insulin secretion to the rise of glucose content in the medium.

Under study was the hypophysis influence on the growth of human melanoma explants, cultivated in the abdominal cavity of mice and rats. The heterotransplants growth was compared in intact and hypophysectomized animals exposed to ACTH, and also the effect of the murine hypophysis explanted into the adjacent chamber compartments on the melanoma explants growth was investigated. The growth was assessed by a square area of the explants growth zones. ACTH and the hypophysis explanted were found to render a stimulating effect on the growth of tumor heterotransplants. Hypophysectomy in rats would suppress the growth of all melanoma explants under investigation. When injecting ACTH into hypophysectomized animals the growth of melanoma heterotransplants in the chambers does not differ from that in control series.

Disturbances of the microvascular permeability were studied by the "vascular labelling" technique during the immobilization stress of hypophysectomized and adrenalectomized rats. Animals with sham operations served as controls. As revealed, hypophysectomy and adrenalectomy caused disturbances of vascular permeability in the mesentery. Vascular permeability disturbances in the hypophysectomized and adrenalectomized rats under conditions of immobilization were more expressed than in the sham-operated animals. Removal of the pituitary and adrenal glands produced mast cell degranulation at the earlier immobilization period.