The thymic factor tactivin prevents ACTH from stimulating steroidogenesis by mouse adrenal cells.

The effect of tactivin, a thymic hormonal factor, (MW 1-6 KD), on the adrenal glucocorticoid function in mice was studied. Tactivin (0.1-2 micrograms/mouse i.p.) produced a slight decrease in plasma corticosterone. The decrease was much more pronounced when tactivin was administered to mice with a high basal level of the hormone. The tactivin supplement had a significant suppressive effect on corticosterone production in both the whole adrenals and the intact isolated adrenal cells. When added at the doses of 0.00064-2 micrograms/ml to the isolated adrenal cells in the presence of ACTH, tactivin abolished the stimulatory effect of corticotropin on corticosterone production. The abolition was complete at a low dose (1.6 microIU/ml) and incomplete, yet significant, at a high dose of ACTH (1600 microIU/ml). The in vitro data are in a good agreement with those obtained in the in vivo experiments. The stimulatory effect of a synthetic analog of cAMP-Dibutyryl-cAMP on the steroidogenesis of adrenal cells was as pronounced as that of ACTH. Nevertheless, tactivin exerted no influence on Bu2-cAMP stimulation. The results indicate that tactivin prevents ACTH from acting on steroidogenesis at some time point preceding the formation of secondary messengers.

Corticosterone treatment affects neonatal induction of immunological tolerance to hen egg lysozyme in mice.

Immunological tolerance to hen egg lysozyme (HEL) was induced in mice by one injection of 0.1 mg of HEL intraperitoneally on day 0 (i.e. within the first 24 h after birth). After immunization with the same antigen 8 weeks later, such mice developed markedly lower numbers of specific antibody-forming cells than did the untreated controls. When the tolerized mice were injected with three doses (1 microgram each) of corticosterone (CN) on days 1, 3 and 5, the tolerogenic effect was markedly diminished. However, in adult animals neither the inducibility of tolerance nor the intensity of immune reaction was influenced by the early treatment with CN. No influence of early CN treatment on the in vitro response of spleen cells to T- and B-cell mitogens was found, when tested in adult animals. The results support a view that neonatally induced immunological tolerance to hen egg lysozyme is mediated by a population of antigen-specific regulatory cells, generation of which can be prevented by treatment with CN.

[The functional characteristics of the hypophyseal-adrenal system in female mice with a hereditary autoimmune pathology]. / Osobennosti funktsionirovaniia gipofizarno-nadpochechnikovoi sistemy u samok myshei s nasledstvennoi autoimmunnoi patologiei.

Functional activity of the pituitary-adrenal axis was studied in genetically autoimmune mice (NZB strain). Young and healthy females (2-3-month old) had high total plasma corticosteroids which sharply decreased by the 6-7th month when the first anti-erythrocyte autoantibodies appeared. At the same time, their ACHT plasma concentration significantly increased compensating, probably, for the low level of corticosteroids. At 6-7 month of age, the amount of corticosteroid-binding globulin was significantly increased therefore decreasing the pool of the active hormones. Low doses of dexamethasone increased the pool of free active glucocorticoids and prevented development of autoimmune processes. The data obtained suggest a possible role of endogenous glucocorticoids in the protection against autoimmune disease.

[Modulation of the circadian rhythm of the glucocorticoid hormone level in mice by thymoptin administration at various times of day]. / Moduliatsiia sutochnogo ritma soderzhaniia gliukokortikoidnykh gormonob u myshei vvedeniem timoptina v raznoe vremia sutok.

A study was made of the level of corticosterone in mouse blood plasma after 4-time daily administration of thymopthin (a drug containing 1% of thymosin-alpha 1, synthesized in the All-Union Research Institute of Technology of Blood Substitution and Hormonal Drugs) at a doze of 0.05 mg per mouse in the morning and evening. The object of investigation was blood plasma of CBA male mice aged 12-16 weeks. The investigation was experimental. The purpose was to elucidate a possible role of thymic hormones in the regulation of circadian rhythm of glucocorticoid function of the adrenal cortex. Plasma concentration of corticosterone was determined by concurrent protein binding of hormones. Thymopthin administration was shown to result in change of circadian rhythm of the level of corticosteroids in mouse plasma. Drug administration in the morning elevated daily concentration of corticosterone, that also evening reduced it as compared to the control group that in the received the same volume of physiological salt solution. A curve of the daily time course was obtained as a result of smoothing by a method of the least squares. These results should be taken into account when using thymic drugs for therapeutic and experimental purposes.

The possible involvement of glucocorticoids in the development of genetically determined autoimmune pathology in NZB mice.

The total blood corticosterone concentration, the reactivity of the adrenal glands to exogenous adrenocorticotrophic hormone, and the binding capacity of corticosteroid-binding globulin (CBG), were determined in male NZB mice that spontaneously develop an autoimmune disease. The appearance of antibodies to endogenous erythrocytes was also monitored. This study was performed on animals of the following age groups: (1) 2-3-month-old animals prior to the appearance of autoantibodies; (2) 6-7-month-old animals in the period when the disease developed; and (3) 10-12-month-old animals, i.e. the period when the autoimmune disease developed. It was demonstrated that in the 10-12-month-old mice there was a sharp decrease in the total corticosterone level in the plasma (from 152 +/- 32 to about 20 micrograms l-1), and the reactivity of the adrenal glands to exogenous corticotrophin decreased (from 400% to 120%). However, the binding capacity of CBG increased with age which led to a decrease in the pool of active corticosterone in the blood. The increase in this capacity was especially pronounced in affected 10-12-month-old animals. (The number of binding sites increased from 0.64 +/- 0.05 to 0.8 +/- 0.03 microM and the values of the association constant for the binding of corticosterone to CBG increased from 0.29 +/- 0.05 to 0.91 +/- 0.07 microM-1). The combination of the above-mentioned changes suggests that there is a direct correlation between the decrease in the glucocorticoid background in the NZB mice and in the appearance of autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of thymosin (fraction 5) and taktivin on adrenocortical function in mice]. / Vliianie timozina (fraktsiia 5) i taktivina na funktsiiu kory nadpochechnikov u myshei.

A study was made of the effect of the thymic factors thymosin (fraction 5) and tactivin on adrenocortical function of BALB/C mature mice. A single administration of thymosin at a dose of 1 micrograms/mouse causes a rise of the blood level of corticosterone in 3 h. Dexamethasone, a blocker of ACTH secretion, stops the thymosin effect. Thymosin does not influence adrenocortical production of corticosterone in vitro. A marked tendency to a decrease in the blood level of corticosterone is clearly observed 3 h after tactivin administration at doses of 0.1, 0.5 and 2.5 micrograms/mouse. Tactivin added to the adrenal glands in vitro causes dose-dependent suppression of corticosterone specific production. A conclusion is that both factors act in opposite directions on adrenal functioning, and their influence on the glands is mediated differently.

Involvement of thymic hormones in regulation of the pituitary-adrenal axis in mice.

The effects of thymic hormone thymosin (fraction 5) and tactivin on the adrenal glucocorticoid function were compared in BALB/c mice. An elevation in plasma corticosterone level was found 3 h after i.p. injection of thymosin (1 microgram/mouse) which was possibly caused by an activation of neuroendocrine structures. This appeared plausible because the pretreatment with dexamethasone (10 micrograms/mouse) abolished the effect of thymosin. In contrast, tactivin produced a decrease in plasma corticosterone if administered to mice with high basal level of the hormone. Tactivin added at doses from 0.00064-2 micrograms/ml together with ACTH (1.6 microIU/ml) to isolated adrenal cells hindered the stimulatory influence of ACTH on the production of corticosterone by the adrenal cells. Thus, the thymic hormone thymosin and tactivin showed opposite influences on the adrenal glucocorticoid function which appeared to be mediated through different mechanisms.

[Effects of taktivin on corticosterone production by a suspension of mouse adrenal gland cells]. / Vliianie taktivina na produktsiiu kortikosterona suspenziei kletok nadpochechnikov myshei.

The influence of the thymic hormone, not imported preparation, taktivin, on the corticosterone production by the mouse (females, BALB/c) isolated adrenocortical cells was investigated. Taktivin (0.08 and 2 micrograms/ml) reliably decreased corticosterone production by the intact cells. After stimulation of the cells by the adrenocorticotropin, the suppressive effect of the thymic hormone was expressed more strongly. On the background of ACTH (1.6 microIU/ml) taktivin (0.00064-0.4 microgram/ml) decreased corticosterone production to a basal level. When the cells were stimulated by ACTH (1600 microIU/ml) taktivin (0.000125-2 micrograms/ml) decreased corticosterone production to a marked degree. These facts witness the important role of taktivin polypeptide components in realization of cooperation between the immune and endocrine systems.

[Effect of thymosin (fraction 5) on the development of functional activity of the adrenals and gonads in genetically athymic mice]. / Vliianie timozina (fraktsiia 5) na formirovanie funktsional'noi aktivnosti nadpochechnikov i gonad u geneticheski bestimusnykh myshei.

The paper is concerned with the effect of thymosin, a hormone secreted by the thymus (fraction 5), on the development of adrenocortical and sex gland functions in genetically athymic mice (nude mutation). Multiple administration of thymosin to mice in the 1st month of their life (0.1 microgram/mouse twice a week) caused the suppression of corticosterone production by the adrenal glands in adult mice aged 2 mos., a considerable rise of the blood level of testosterone in male mice and the reduction of the specific production of estradiol by the ovaries in females. A thymosin-mediated role in the interaction between the immune and endocrine systems in the period of development of their functions was discussed.

[Effects of thymosin (fraction 5) on the endocrine function of the testis in mice]. / Vlianie timozina (fraktsii 5) na éndokrinnuiu funktsiiu semennikov u myshei.

The influence of the thymic hormone thymosin (fraction 5) on the hormonal function of testes form 2 months old BALB/c mice was investigated. It was shown that after 3 and 24 hours after thymosin administration there is a considerable decrease of plasma testosterone level as compared with the level of control animals, which were injected with BSA. 24 hours after administration of thymosin the in vitro production of testosterone by the testes was decreased essentially as compared with the control. Thymosin, injected together with indomethacin, inhibitor of prostaglandin synthesis, does not influence the hormonal activity of the testes. So, it was ascertained that thymic hormone thymosin participates in the regulation of the testes hormonal function. It is supposed that it's action on the gonads may be carried out through prostaglandins.

Evidence for thymus involvement in development of adrenal and gonadal endocrine functions in mice.

The endocrine function of the gonads and adrenals was studied in mice with congenital athymia (mutation nude); in normal mice thymectomized at 3 days of age and in congenitally athymic mice with thymic transplants from the 5th day of life. The data demonstrated that abnormal function of the adrenals and testes in nude mice is related to the absence of a functionally active thymus during early ontogenesis. The effect of thymosin (fraction 5) on the formation of adrenal functional activity was studied in congenitally athymic and normal mice. Treatment with thymosin during the first days of life resulted in suppressed adrenal function in adult athymic and normal mice. When given to adult normal mice, thymosin also decreased adrenal function. It is suggested that the thymus and its hormone thymosine are of importance in the formation of endocrine functions during the postnatal period in mice.

[Influence of the thymus on the endocrine function of the gonads and adrenals in mice]. / Vliianie timusa na endokrinnuiu funktsiiu gonad i nadpochechnikov u myshei.

Congenitally athymic (nude) mice show significant disorders of endocrine functions of the gonads and adrenals. Transplantation of the thymus to such animals in the first days of life entails the normalization of the functions of the adrenals and testes but not of the ovaries in adult animals. It is inferred that abnormalities in the functions of the testes and adrenals in nude mice are consequent on the lack of the thymus in the early stages of ontogenesis.

[Role of the thymus in producing the endocrine function of the testes in mice]. / Rol' timusa v formirovanii éndokrinnoi funktsii semennikov u myshei.

The thymic effect on the mouse gonadal endocrine function was studied. The serious gonadal endocrine dysfunction was seen in mice with genetically determined absence of the thymus. Thymectomy of healthy animals aged 3 days induces similar disorders. Transplantation of the thymus to the genetically thymus-free animals during the first days of the life returns this function to normal. It is concluded that the thymus plays an important role in the formation of the mouse gonadal endocrine function.

[Mechanisms of the immunodepression caused by ortho-aminoazotoluene and its noncarcinogenic analog in mice]. / Mekhanizmy immunodepresii, vyzvaemoi u myshei u myshei orto-aminoazotoluolom i ego nekantserogennym analogom.

Single injections of ortho-aminoazotoluene (OAT) or aminoazobenzene (AB) decrease the immune response of DD mice to the strain-nonspecific Krebs-2 tumor. The immunosuppressive action of AB is due to its toxicity for lymphoid cells, whereas the OAT effect is mediated by adrenal glands. After OAT injection,II-oxycorticosteroids level is elevated although their production by adrenal glands is not increased. The accumulation of glucocorticoids in blood after OAT injection is assumed to be the result of a decreased hormone utilization because of the blockade of receptor proteins or metabolizing enzymes in liver cells by a carcinogen.