[Role of calcium ions and cyclic nucleotides in the regulation of somatotroph functional activity in rats as a function of age]. / Rol' ionov kal'tsiia i tsiklicheskikh nukleotidov v reguliatsii funktsional'noi aktivnosti somatotrofov krys v zavisimosti ot vozrasta.

Somatotropic hormone (STH) biosynthesis and secretion were studied in primary adenohypophyseal cultures of neonatal, prepubertal, and adult rats. It was shown by disc PAAG electrophoresis of products synthesized in incubation of neonatal rat hypophyseal cells that L-14C leucin incorporates predominantly in the STH containing fraction. The share of prelabeled STH secreted into the culture virtually did not depend on the age of animals, this indicating the maturity of mechanisms of basal somatotroph secretion as early as in the neonatal period of development. Ca-regulating agents (ionophore A23187, EGTA) caused quantitatively similar changes of somatotroph secretory activity in cultures of hypophyseal cells from rats of different ages. At the same time, clear-cut age-specific features of stimulating effect of dibutyryl derivatives of cAMP and cGMP on secretion of immunoreactive STH were detected. The results indicate that somatotropic function in neonatal hypophysis is a dominant one and demonstrates increased reactivity to secretogenic action of cyclic nucleotide analogs.

[The effect of insulin on protein synthesis and secretion in primary liver cultures]. / Vliianie insulina na sintez i sekretsiiu belkov v pervichnykh kul'turakh kletok pecheni.

The effects of insulin on the rates of synthesis of intracellular and secreted proteins have been studied in primary cultures of fetal rat hepatocytes. During 3-h incubation with the hormone and 14C-L-leucine similar stimulation of synthesis of both intracellular and secreted protein was observed. Insulin did not affect significantly the proportion of 14C-labelled proteins destined for secretion in the cell cultures grown on standard nutrient medium, as well as on selective medium containing phenobarbital and cortisol. The results obtained show that the major part (85-90%) of newly synthesized proteins remains inside the cells. Therefore, biological testing of insulin or its synthetic analogs on hepatocyte cultures may be limited by the estimation of the rate of biosynthesis of intracellular proteins only.

[Effect of steroid hormones and noradrenaline on somatotropin hormone secretion by primary cultures of hypophyseal cells of rats of various ages]. / Vliianie steroidnykh gormonov i noradrenalina na sekretsiiu somatotropnogo gormona pervichnymi kul'turami gipofizotsitov krys razlichnogo vozrasta.

Dexamethasone and aldosterone in concentrations 10(-8) to 10(-6) stimulated STH secretion by hypophyseal cells of neonatal and adult rats under conditions of prolonged (72 h) incubation of primary cultures. Corticosterone and progesterone had a stimulating effect on STH release by hypophyseal cells. Long exposure of cultured suckling rat cells to dexamethasone resulted in increase of STH basal secretion and enhanced the stimulating effect of low concentration (10(-7) mole) of noradrenaline on STH release during a subsequent short (2 h) incubation. The results permit us to suggest that development of hypophyseal somatotropic function observed in the postnatal period may be to a certain measure explained by combined effects of corticosteroids and catecholamines.

[The possible participation of gap junctions in the realization of the effects of stimulators of secretory processes in the hypophysis]. / Vozmozhnoe uchastie shchelevykh kontaktov v realizatsii éffektov stimuliatorov sekretornykh protsessov v gipofize.

Sodium butyrate and octanol did not change the basal rate of GH secretion. However, octanol completely and partially suppressed GH release stimulated by thyroliberin and DbcAMP, respectively. Octanol did not influence GH secretion induced by DbcGMP. Besides, octanol did not change significantly basal prolactin release, but this agent blocked secretogenic action of on lactotrophs. The results show the important role of cell-to-cell communication mediated by gap junctions in stimulatory action of thyroliberin and cAMP analogue on GH release from neonatal pituitary cells, as well as in secretogenic action of thyroliberin on lactotrophs.

[Age-related differences in macromolecule biosynthesis reactions in rat pituitary cells to catecholamine, serotonin and acetylcholine]. / Vozrastnye razlichiia reaktsii biosinteza makromolekul gipofizarnykh kletok krys na katekholaminy, serotonin i atsetilkholin.

In experiments using primary monolayer cultures norepinephrine, isoproterenol, and serotonin (10(-6)-10(-5) M) inhibited the rate of total protein biosynthesis more effectively in pituitary cells of pubertal and sexually mature rats as compared to neonates and prepubertal animals. Acetylcholine (10(-5)M) reduced the rate of total protein synthesis in pituitary cells of pubertal rats but did not change this parameter of functional activity in pituitary cells of neonatal animals. Norepinephrine and isoproterenol inhibited the rate of DNA synthesis in pituitary cells of newborn rats whereas serotonin and acetylcholine were of no avail in this respect. These results permit us suggest an important role of neurohumoral agents in regulation of rat pituitary cells growth and functional activity during the postnatal development.

[Increased sensitivity of hypophyseal cells from neonatal rats to bromocriptine and melatonin]. / Povyshennaia chuvstvitel'nost' gipofizarnykh kletok neonatal'nykh krysiat k bromokriptinu i melatoninu.

Age-related peculiarities of the bromocriptine and melatonin effect on macromolecule biosyntheses in cultured rat pituitary cells were studied during long-term (3 day) incubation. Bromocriptine (10(-9)-10(-7) M) caused dose-dependent inhibition of DNA synthesis in pituitary cells of neonatal rats, but only in maximal dose (10(-7) M) it decreased significantly this parameter in pituitary cells of adult animals. Melatonin (10(-8)-10(-6) M) caused significant inhibition of DNA synthesis in cultured cells of neonatal rat pituitaries. However, melatonin did not change DNA biosynthesis in pituitary cells of adult rats. The results obtained permit us to suggest certain contribution of dopaminergic tone and melatonin to the control of proliferative activity of rat pituitary in neonatal period of development.

[The cytoarchitectonics of the adenohypophysis in light of the concepts of cellular flows]. / Tsitoarkhitektonika adenogipofiza v svete predstavlenii o kletochnykh potokakh.

Analysis of published data allows to suggest a possible model of adenohypophyseal cytoarchitectonics based on the concepts of tissue self-renewal and streaming in this gland. The model provides a framework for understanding: a) the existence of ambiguous cellular elements; b) change of relationship between different types of hormone secreting cells with sex-dependent prevalence of somato- or lactotrophs; c) relatively high proliferative activity of lactotrophs in mature pituitary gland; d) specific spatial arrangement of various types of hormone secreting cells; e) multiple effects of some bioregulators on the secretion of two or more pituitary hormones; f) the existence of polyfunctional pituitary adenomata containing and secreting several adenohypophyseal hormones simultaneously. Possible approaches to thorough evaluation and testing of the model in experiments using organ or cell cultures of adenohypophysis are discussed.

[Secretory activity of lactotrophs and its regulation by hypothalamic hormones in primary cultures of pituitary cells of rats of different ages]. / Sekretornaia aktivnost' laktotrofov i ee reguliatsiia gipotalamicheskimi gormonami v pervichnykh kul'turakh gipofizarnykh kletok krys raznogo vozrasta.

Basal prolactin (PRL) secretion and the responses of lactotrophs to thyroliberin, dopamine and somatostatin were studied in the experiments employing primary monolayer cultures of pituitary cells obtained from developing rats of different ages. High responsiveness of PRL-secreting cells to the action of hypothalamic hormones was observed in the group of neonatal rats, although basal PRL release was about two orders lower in pituitary cultures of neonatal rats as compared to the cultures of immature, pubertal and adult animals. The investigation performed could reveal quantitative, but not qualitative differences in the reactions of lactotrophs of various age groups. It is concluded that postnatal development in the rat is coupled with significant changes of basal PRL release and to a lesser extent, with changes of lactotroph responsiveness to hypothalamic hormones.

[Enhanced sensitivity of pituitary cells to corticosteroids in neonatal rats]. / Povyshennaia chuvstvitel'nost' gipofizarnykh kletkok neonatal'nykh krysiat k kortikosteroidam.

The effects of corticosteroids on pituitary cells, obtained from developing rats of different ages, were studied during long-term (3-4 days) incubation. Dexamethasone, cortisol and aldosterone inhibited the rate of DNA synthesis in primary cultures of pituitary cells from neonatal and pup rats more efficiently than in cell cultures of prepubertal and adult animals. Moreover, the above mentioned corticosteroids inhibited total protein biosynthesis in pituitary cells of infantile rats and did not change significantly this index of functional activity in cells of prepubertal and adult animals. In separate experiments steroid specificity of glucocorticoid action was examined in detail: estradiol and testosterone did not change the rates of macromolecule synthesis in neonatal pituitary cells whereas progesterone possessed a weak inhibitory effect that was, however, far less marked as compared to the effect of corticosterone. It has been concluded that neonatal rat pituitary cells demonstrate enhanced sensitivity to anti-proliferative and catabolic action of corticosteroids.

[Reactions of rat fetal hepatocytes to hormones in primary cultures grown in selective media with an addition of glucocorticoid and barbiturate]. / Reaktsii gepatotsitov plodov krys na gormony v pervichnykh kul'turakh vyrashchennykh v selektivnoi srede s dobavleniem gliukokortikoida i barbiturata.

After growing of fetal rat hepatocytes in the medium containing cortisol and sodium barbital for 4-8 days and subsequent cultivation in the medium without glucocorticoid and barbiturate for 1-4 days insulin retained its ability to stimulate total RNA and protein synthesis, while human growth hormone kept its enhancing action on RNA biosynthesis. However, cortisol did not change protein synthesis and inhibited paradoxically incorporation of 3H-uridine into total RNA, after preincubation of cells in the selective medium. This suggests that prolonged exposure of cultured fetal rat liver cells to cortisol and sodium barbital may cause phenomena similar to those of hormonal and/or enzymatic imprinting.

[Effects of dibutyryl derivatives of cyclic nucleotides on synthesis of total RNA and proteins in cultured fetal rat hepatocytes]. / Vliianie dibutirilproizvodnykh tsiklicheskikh nukleotidov na sintez summarnykh RNK i belka v kul'tiviruemykh gepatotsitakh plodov krys.

During short-term (6 h) or long-term (24 h) incubation of fetal rat liver cells in primary cultures, 10(-3) M dibutyryl-derivative of cyclic AMP (Bt2cAMP) and sodium butyrate decreased total RNA and protein synthesis. In contrast, dibutyryl-cyclic GMP (Bt2cGMP) at the same dose (10(-3) M) was without significant effect on RNA and protein biosynthesis. During short-term (4 h) incubation 10(-3) M Bt2cAMP and Bt2cGMP stimulated serum albumin production, while sodium butyrate was without effect. In long-term (22 h) incubation only 10(-3) M Bt2cAMP noticeably increased albumin production. The results obtained clearly show that Bt2cGMP, unlike Bt2cAMP, is not able to modify significantly total RNA and protein synthesis in cultured fetal rat liver cells. It is concluded also that the effects of dibutyryl-derivatives of cyclic nucleotides, at least on albumin production, are not mimiebet by butyrate.

[The direct stimulating action of thyroliberin on the biosynthesis of total protein in cultured liver cells of rat fetuses]. / Priamoe stimuliruiushchee vliianie tiroliberina na biosintez summarnogo belka v kul'tiviruemykh kletkakh pecheni plodov krys.

In experiments using fetal rat liver cultured cells TRH was shown to stimulate total protein synthesis but not RNA synthesis during long incubation. Somatostatin affected neither protein synthesis nor RNA synthesis in cultured liver cells. Possible physiological role of peripheral TRH during perinatal period in the rat is discussed.

[An analysis of the distribution by molecular weight of an aggregate of biologically active compounds taking into account their possible penetration through gap-junction channels]. / Analiz raspredeleniia po molekuliarnoi masse sovokupnosti biologicheski aktivnykh soedinenii s uchetom ikh vozmozhnogo proniknoveniia cherez kanaly shchelevykh kontaktov.

Analysis of molecular weight distribution of most well-known biologically active compounds demonstrates that all known types of bioregulatory compounds, excluding most peptides, have molecular mass less than 800 Da, i.e. they may penetrate the gap junction channels and, hence, play a part of intratissue regulators. Possible consequences of the analysis performed for understanding the role of neurohumoral regulation in phylogenesis and ontogenesis of multicellular eukaryotes have been discussed.

[The effect of dibutyryl derivatives of cyclic nucleotides on albumin production in a primary culture of rat liver cells]. / Osobennosti vliianiia dibutirilproizvodnykh tsiklicheskikh nukleotidov na produktsiiu al'bumina v pervichnykh kul'turakh kletok pecheni krys.

Dibutyryl-derivative of cyclic AMP (Bt2cAMP, 10(-3)M) affected the basal and cortisol-induced production of immunoreactive serum albumin (SA) in primary cultures of fetal rat liver cells by the type of two-phase time dependency. The same two-phase character exhibited dose-dependent effect of Bt2cAMP (10(-5)-10(-3)M) on SA production in cultured liver cells obtained from fetal and 3 weeks old rats. Similar two-phase dose- and time-dependent effects demonstrated Bt2cGMP (10(-5)-10(-3)M), although certain differences were detected when either action of Bt2cAMP and Bt2cGMP or response of cultured liver cells from fetal and early postnatal rats to these drugs were studied. The data obtained suggest that normal liver cells are provided with feed-back mechanism which limited the cellular reaction to cyclic nucleotides under experimental conditions involving, potentially excessive doses and/or time of action of these agents.