The efficiency of calcitonin transport across the C-cell-blood barrier in rat thyroid.

This paper studies calcitonin (CT) transport across the C-cell-blood (CCB) barrier in normal rats. The efficiency of this transport is expressed as endogenous calcitonin bioavailability (F(CT)), i.e., that portion of CT molecules extruded by the thyroid C-cell basal pole that enters the circulating blood. Because currently F(CT) cannot be estimated directly, a novel methodology was used for its estimation. The essence of this methodology is to assess the CT level before and after the CCB barrier, to study these input-output CT relationships mathematically, and to find the F(CT) range allowed by the relationships. In this context, the subplasmalemmal granule numerical density in the C-cell basal pole (X) and the CT concentration in the right ventricular blood (Y) were found to be highly correlated: r(xy) = 0.922, P < 0.001; the covariance coefficient rho(xy) = 0.9980, P < 0.0001. Clearly, the overall variance of these input-output relationships in the covariance model (square root Var(xy) = 6.32) is explained, specifically, by CT retention (R(CT)) variability at the CCB transport stages. The greater the R(CT) mean value in the studied rats, the greater is the impact of R(CT) variability on Var(xy). The estimated variance caused by R(CT) (Var(CCBR)) makes it possible to determine R(CT) and F(CT) (F(CT) = 100% - R(CT)). Thus we estimated Var(CCBR) as Var(CCBR) < Var(xy) - CV(RIA)(2), where CV(RIA)(2) is CT assay variance: square root Var(CCBR) = 6.00% (P > or = 0.95). We then estimated F(CT) as the value range that does not contradict the Var(CCBR) obtained: 62% < F(CT) < 100% (P > or = 0.95).

[Interrelations of morphological parameters in the system of neuroendocrine regulation following longterm morphine administration]. / Vzaimootnosheniia morfologicheskikh parametrov v sisteme neiroéndokrinnoi reguliatsii pri dlitel'nom vozdeistvii morfina.

To study the morpho-physiological changes of the nervous and endocrine regulatory systems following long-term influence of morphine hydrochloride, morphometric and correlation analysis of the structural components of the cerebral cortex, hypothalamus, adenohypophysis and thyroid gland was performed. The interrelation between the values of some parameters and the dose of morphine hydrochloride, that caused the tolerance to the drug, was shown. Dose-dependent effect was found in the degree of morphological remodeling of organ components that was demonstrated by the changes in cell and nuclear dimensions, staining properties of cytoplasm, ultrastructural components of thyrocytes, neurons and their processes, hormonal background, the number of the functioning blood capillaries. Interrelations of the morphological parameters are demonstrated by the correlations of different strength and direction.

[Study of the endogenous calcitonin transport in the rat thyroid gland]. / Issledovanie transporta éndogennogo kal'tsitonina v shchitovidnoi zheleze krysy.

Regression analysis revealed a significant correlation between Nvsq and calcitonine. The regression model was then transformed into a covariation one to establish: 1) probability of all calcitonine molecules moving across the C-cell-blood barrier into the blood, 2) confidence interval of endogenous calcitonine bioavailability, and 3) estimate of the period of calcitonine half-retention by the C-cell-blood barrier.

[The efficiency of the calcitonin-transporting activity of the hemato-C-cellular system in the thyroid gland]. / Effektivnost' kal'tsitonin-transportiruiushchei deiatel'nosti gemato-C-tselliuliarnoi sistemy v shchitovidnoi zheleze.

The efficiency of hemato-C-cellular transport of calcitonin into the systemic blood flow was evaluated by the methods of statistical modelling. The linear regression model obtained on 36 rats suggests essential predetermination of the serum concentrations of calcitonin (CT) by the intensity of incretory activity of the thyroid parafollicular epithelium: CT = 13.733+ (0.318 Nvsg; rxy = 0.830; p < 0.001 (Nvsg is numerical density of the sublemmal granules on the C-cells vascular pole). At the same time, the resulting index (CT) depends not only on Nvsg. This index is also influenced by the factors not controlled by the model, such as Hemato-C-cellular delay of calcitonin. These factors determine each certain proportion of the error of prognostication of the calcitonin serum content according to Nvsg. A covariation model CT = bNvsg was plotted in order to determine the total influence of uncontrolled factors. Its error of prognostication was subject to analysis of variance and a confidence interval of biological accessibility of endogenous calcitonin was calculated (73% < FCT < or = 100%; p > or = 0.95). The results obtained suggest the absence of essential intrathyroid loss of calcitonin at the transinterstitial and transmural stages of hemato-C-cellular hormone transfer.

[The postnatal development of the hemato-C-cellular system in the thyroid of rats sympathectomized with guanethidine]. / Postnatal'noe razvitie gemato-C-tselliuliarnoi sistemy v shchitovidnoi zheleze desimpatizirovannykh guanetidinom krys.

We used ultrastructural morphometry to examine submicroscopical organization of spatial contacts between the C-cells and perifollicular hemocapillaries in the thyroid gland of 2-, 4-, 12-, 26-, and 52-week-old rats desympathized with guanetidine. We found that desympathization does not affect typology of ultrastructural elements of the hemato-C-cellular complex, and predominant coupling of the vascular pole of the C-cell with peripheral zone of endotheliocyte highly effective in terms of transport. Postnatal changes of certain parameters of the hemato-C-cellular system, however, undergo some statistically significant changes. Under experimental conditions, we observed the formation of hemato-C-cellular contacts simultaneously involving two C-cells.

[The dynamic postnatal morphogenesis of the hemato-C-cellular interrelations in the rat thyroid gland]. / Dinamika postnatal'nogo morfogeneza gemato-C-tselliuliarnykh vzaimootnoshenii v shchitovidnoi zheleze krysy.

The system of hemato-C-cellular interactions in the thyroid gland of rats at the age of 2, 4, 12, 26, and 52 weeks is characterized by similar submicroscopical organization: the typology of hemato-C-cellular complex is preserved during ontogenesis and predominant coupling of the vascular pole of C-cell to the highly effective peripheral zone of the endotheliocytes with reference to the transport is provided. Ultrastructural changes in the zones of the perifollicular hemocapillaries facing the vascular fields of C-cells reflect the dynamics of functioning of the hemato-C-cellular system at different stages of postnatal morphogenesis.

[A method for determining the formal boundary of the hematocellular interaction zone]. / Sposob opredeleniia formal'nykh granits zony hematotselliuliarnogo vzaimodeistviia.

A method of standard marking of the boundaries of hematocellular interaction zone is proposed. It is intended for identification of most effective transport zone of hematocellular conjugation. The main point of the method is to find minimal zone of the investigated hematocellular interface, the expansion of which will be accompanied by an increment of the perimicrovascular interstitium mean thickness. To verify the method applicability, a stereometric study is carried out on hematocellular barrier formed by thyroid C-cells and perifollicular hemocapillaries. The proposed method has a negligible error and provides accurate ultrastructurometry of blood-cell barriers.

[A stereometric method for the single-criterial evaluation of the incretory activity of the thyroid parafollicular epithelium]. / Stereometricheskii sposob monokriterial'noi otsenki inkretornoi deiatel'nosti tireoidnogo parafollikuliarnogo épiteliia.

A stereometric value of secretion of the thyroid C-cell is developed. The method is based on the count of sublemmal secretory granules. To verify the method applicability, a correlation analysis is carried out.

[The compensatory-adaptive reactions of the thyroid and adrenal adrenergic structures in the postnatal ontogeny of sympathectomized rats]. / Kompensatorno-adaptatsionnye reaktsii adrenergicheskikh struktur shchitovidnoi zhelezy i nadpochechnikov v postnatal'nom ontogeneze desimpatizirovannykh krys.

The study was performed in albino rats treated during first two postnatal weeks with guanetidin isotonic solution injected subcutaneously in dose 20 mg/kg body weight to obtain desympathization. Control animals received similar volume of the solution during equal terms. Thyroid and adrenal glands were studied in 1- and 6-month-old rats both by light and electron microscopes. Serotonin and catecholamines were revealed by fluorescent-histochemical method. In experimental 1-month-old animals morphological indexes indicate the thyroid gland hyperfunction. In these animals serotonin and catecholamines content is lower in parafollicular endocrinocytes, mast cells and in adrenergic fibres, the density of which is significantly lower than that in control animals. The adrenal gland weight in experimental animals increases due to the medulla. Serotonin and catecholamine content is essentially higher. Thyroid gland in 6-month-old experimental rats is hyperfunctioning. Adrenal fibres density in its stroma is close to control indexes. Catecholamines and serotonin adrenal glands medulla grows with age and remains higher than the appropriate control level, which indicates active participation of adrenal glands in adaptive reactions is desympathized animals. Serotonin plays an important role in local regulation of thyroid glands. Parafollicular endocrinocytes perform the function of local biogenic amines-producers, while mast cells regulate the serotonin content.

[Thyroid morphofunctional changes in various types of experimental chronic stress]. / Morfofunktsional'nye izmeneniia shchitovidnoi zhelezy pri razlichnykh variantakh khronicheskogo éksperimental'nogo stressa.

Structural and functional parameters of the thyroid were studied in mature rabbits, inducing stress by stimulating the ventromedial nucleus of the hypothalamus or by exposing the animals to electrocutaneous irritations. Morphometric and radioimmunoassay results have revealed thyroid activation during the adaptation syndrome. Prolonged intensive stress was shown to cause a decrease in thyroid secretory activity, reflecting change of a stage of stable resistance by a phase of depletion of compensatory resources. However the nature of changes in the blood levels of thyroid and thyrotropic hormones in experimental animals have some characteristic features. A conclusion was made of the correlation between pathogenesis of the general adaptation syndrome and a methodological approach to simulation of a body tension reaction.

[Effects of chronic experimental stress and endogenous opioids on histophysiological parameters of the thyroid gland]. / Vliianie khronicheskogo éksperimental'nogo stressa i éndogennykh opioidov na gistofiziologicheskie parametry shchitovidnoi zhelezy.

In adult rabbits stress was modelled by electrostimulation of the hypothalamus ventromedial nucleus (15-hour-long session during 30 days) and medulla's raphe big nucleus which is one of the central places of the opioid peptides synthesis was irritated. It is revealed, that under stress thyroid gland responds by serum T3 increase in comparison with control animals with statistically significant variability of the T4 profile. Chronicity of the emotional agitation involves destructive changes in the thyroid parenchyma the hurting effect of the negative emotional factor is expressed less during opioid peptides complex activation. It is suggested that there are its own stress-limiting mechanisms in thyroid gland.

[Effects of dosed sympathectomy on the development of adaptation-compensation reaction of C-cells of the thyroid gland and chromaffin cells of the adrenal glands in young rats]. / Vliianie dozirovannoi desimpatizatsii na razvitie adaptatsionno-kompensatornykh reaktsii C-kletochnogo apparata shchitovidnoi zhelezy i khromaffinotsitov nadpochechnikov u krys rannego vozrasta.

Using radioimmunological, morphometrical, electron microscopic and luminescent methods, comparative analysis of thyroid C-cells and adrenal chromaffin cells has been carried out at guanethidine sympathectomy in young rats. Significant decrease of functional activity of C-cells with concomitant hyperplasia of C-cells population under blockade of sympathetic influences has been revealed. Compared to C-cells, adrenal chromaffinocytes of sympathectomized rats possess higher degree of structural-functional mobilization and are characterized by intensive secretion of catecholamines directed at restoration of tissue neurotransmitter deficit.

[Compensatory-restorative processes of the thyroid gland in 1- and 3-month-old rats in health and in desympathization]. / Kompensatorno-vosstanovitel'nye protsessy shchitovidnoi zhelezy 1- i 3-mesiachnykh krys v norme i pri desimpatizatsii.

In 172 white male rats 1- and 3-month-old, using electron microscopical, autoradiographical, morphometrical and radioimmunological methods, analysis of structural-functional changes of the thyroid gland has been carried out both under normal conditions and at guanethidine desympathization (15 mg/kg for 14 days after birth). Resection of 2/3 of the organ has been performed on the 3d, 5th, 7th and 15th days before sacrifice. In the 1-month-old desympathized rats hypofunctional state of the gland is observed. By the 3d month at the expense of an increased production of thyrotropin and calcitonin the thyroid status becomes normal. The dynamics of the restorative processes in the thyroid gland after resection of 1/3 of the organ in the control and test rats occurs with a similar intensity. Proliferative potency of the desympathized thyroid tissue is much higher.

[Characteristics of the recovery processes in the resected thyroid of adult rats after sympathectomy]. / Osobennosti vosstanovitel'nykh protsessov rezetsirovannoi shchitovidnoi zhelezy vzroslykh krys pri desimpatizatsii.

The investigation was carried out on 65 adult white male rats (12-month-old) after normal development or chemical sympathectomy by guanethidine and subtotal thyroidectomy. By means of electronic microscopic, autoradiographic and radioimmunological methods the increased functional activity in thyroid gland of chemically sympathectomized rats was found. This is mainly due to thyrotropin hyperproduction and intensification of proliferative potential of the organ. Partial resection of sympathectomized rats thyroid gland leads to exhaustion of adenohypophysis compensatory potential manifested in disjunction of integrative connections in hypothalamus-hypophysis-thyroid gland system and delay of thyroid status normalization.

[Effect of adrenergic innervation on the degree of reparation of the thyroid after its resection]. / Vliianie adrenergicheskoi innervatsii na stepen' reparatsii shchitovidnoi zhelezy posle ee rezektsii.

The time course of thyroid functional changes in normal and in partial desympathization was observed in experiments on 250 albino male rats aged 15 days, 1, 3, 6, 12 and 24 mos. Desympathization was induced by the administration of guanethidine at a dose of 15 mg/kg of body mass in the first 14 days after birth. Resection of the two thirds of the gland was performed on the 3rd, 5th, 7th, 15th and 30th days before killing. T3, T4, CT and TSH levels were determined by radioimmunoassay. Analysis of thyroid hormonal patterns showed variability of functional changes of this organ in desympathization. Desympathization at the age of 15 days and one month led to thyroid functional suppression, later on a rise of hormonogenesis was noted as a result of enhanced production of the pituitary body and CT. At the age of 1 and 3 mos. after thyroidectomy the rates of implementation of thyroid reparative potentials in desympathization were much higher than those in controls and were accompanied by a more marked increase in TSH. At the age of 12 mos. the resection of the two thirds of the thyroid caused a progressive decrease in the level of serum TSH which determined a decrease in the rate of normalization of the thyroid status.

[Dynamics of postnatal histogenesis of the thyroid in normal rats and after sympathectomy]. / Dinamika postnatal'nogo gistogeneza shchitovidnoi zhelezy krys v norme i pri desimpatizatsii.

The changes of the thyroid gland and neurocytes of the cranial sympathetic ganglia were followed in rats of different ages after guanethidine injections with the use of radioimmunological assay, electron microscopy and morphometry. The injection of 15 mg of the drug per kg of body weight within the first two weeks after birth caused the death of over 80% of the cells in the sympathetic ganglion. In the sympathectomized 15-day- and 1-month-old rats the functional activity of the thyroid gland was markedly reduced. Later on, intrathyroid hormonogenesis somewhat increases due, apparently, to partial recovery of the organ adrenergic innervation and increase in the production of thyrotropic hypophysial hormone and calcitonin.

[Characteristics of the compensatory repair processes in the thyroid of 1-month-old rats as affected by sympathectomy]. / Kharakteristika kompensatorno-vosstanovitel'nykh protsessov shchitovidnoi zhelezy odnomesiachnykh krys v usloviiakh desimpatizatsii.

A considerable decrease in the amount of sympathetic nervous cells in neonatal rats injected guanethidine resulted in the depression of thyroid gland functional activity in 1-month-old animals, there was an apparent parallel increase in the proliferative activity of the gland. A 2/3 thyroidectomy led to the functional tension of the remaining part of the organ. A comparison of compensatory-reparative processes after thyroidectomy has shown similarity of reparative changes in experimental and control rats, however, the degree of repair potential was much higher in the sympathectomized thyroid gland.