Responses of serum corticosterone and corticosteroid-binding globulin to acute and prolonged stress in the rat.

Responses of serum corticosterone (B) and corticosteroid-binding globulin (CBG) to ether anesthesia (a "classic" acute stress) and to a number of stressors influencing metabolic homeostasis--fasting, physical exercise, cold exposure, and water deprivation--were studied in male and female rats. Metabolic stressors included placing in an ice bath, physical exercise (swimming), fasting for 2 d, swimming after fasting for 2 d, cold-room (4 degrees C) exposure for 2 d, fasting in combination with cold-room exposure for 1 d, and water deprivation for 2 d. The study demonstrated clear differences between males and females in basal B levels and B responses to some stressors. Only ether anesthesia and fasting resulted in similar B levels in males and females whereas in control and all other groups serum B levels were higher in females. Serum CBG was considerably higher in females. In females, ether, swimming, swimming after fasting, fasting, and fasting during cold exposure resulted in a decrease in circulating CBG. Ice bathing and cold exposure did not influence CBG, and water deprivation elevated serum CBG. In males, animals subjected to fasting and fasting during cold exposure had CBG levels lower than control animals. Other groups did not differ from the control. Higher CBG levels in females counterbalanced higher total B in setting circulating free B: significant sex differences in free B were observed only after swimming or fasting during cold exposure. Stress-responsive changes in CBG levels seem to contribute little to changes in free B; the main contributing factor is the rise in total B. However, CBG may play a special role, independent of the functions of corticosteroids. It is proposed that the need for substantial mobilization of spare fuel (as it takes place during physical exercise or fasting) is critical in involving CBG in the stress response.

Increased corticosteroid binding capacity of plasma albumin but not of corticosteroid-binding globulin caused by ACTH-induced changes in free fatty acid concentrations in snowshoe hares and rabbits.

Free fatty acids (FFAs) are rapidly mobilized by ACTH and have been shown to be potent endogenous modulators of steroid-protein interactions. We increased FFA in lagomorphs by ACTH and then separated the transient increase in glucocorticoid binding capacity of plasma into that accounted for by changes in binding to albumin and to corticosteroid-binding globulin (CBG). Sequential injections of dexamethasone and ACTH into both snowshoe hares and laboratory rabbits resulted in the rapid mobilization of FFA only after the ACTH injection. The maximum corticosteroid binding capacity increase paralleled that of the FFA increase in both species. In rabbits, CBG levels remained constant over the duration of the experiment. Corticosterone binding by rabbit albumin increased in a dose-dependent fashion in response to increases in FFA (oleic and linoleic acid) concentrations. Finally, by stimulating FFA release in snowshoe hares with ACTH and separating the increase in corticosteroid binding capacity through selective denaturing of CBG by heat, we determined that the increase in plasma binding capacity was a response to changes in binding by albumin, not CBG. Thus FFA released in response to stressors in lagomorphs may effect short-term increases in steroid binding.

[Pleiotropic physiological effects of mutation di, which determines diabetes insipidus in rats]. / Pleiotropnye fiziologicheskie éffekty mutatsii di, determiniruiushchei nesakharnyi diabet u krys.

The main phenotypic expression of mutation di is diabetes insipidus, which is pronounced in didi homozygotes. Additional physiological traits have been revealed that are associated with diabetes insipidus and are accounted for by the pleiotropic effect of gene di on the function of the reproductive system, metabolism of neurotransmitters in brain, and central regulation of the stress response. In didi mutants, the age-related decrease in fertility is retarded, the increase in B monoamine oxidase activity associated with aging is shifted to an older age, and the level of corticosteroid-binding globulin is decreased in young animals.

Corticosteroid and immune responses to cardiac surgery.

Serum corticosteroid-binding globulin (CBG) and cortisol levels as well as subsets of circulating immunocompetent cells (ICCs) were measured during cardiac surgery. Closed heart surgery (closed mitral commissurotomy) resulted in an elevation of cortisol levels (up to 32 +/- 5 micrograms/dL by the end of the surgery) with no changes in CBG and ICC levels observed. Open heart surgery (open reconstruction of the mitral valve) in surface-induced hypothermia (without extracorporeal bypass) caused a dramatic drop in CBG activity (from 250 +/- 17 microM before the beginning of anesthesia to 198 +/- 15 microM by the end of cooling (just before cardiac arrest) and 158 +/- 13 microM after 30 min of reperfusion), whereas cortisol levels were only slightly elevated by the end of cooling, and a significant increase (up to 17 +/- 2 micrograms/dL) was observed only at the end of the surgery (60 min of reperfusion and warming). Similar to CBG, a significant decline in circulating ICC contents occurred in response to cooling and circulatory arrest.

The interaction between interleukin-1 and glucocorticoids in the in vivo antibody response of mice to three concentrations of antigen.

Antigenic challenge leads to a transient increase of serum glucocorticoids, a phenomenon that has been implicated in regulation of the magnitude of the immune response. In the present study, we determined the effects of immunization with three different doses of the T-dependent antigen, sheep red blood cells (SRBC), on glucocorticoid levels, IL-1 production by splenic macrophages, and number of splenic antibody-forming cells in mice. Immunization with three doses of antigen caused a dose-dependent increase in serum glucocorticoid after 2-4 h. No effect of immunization on serum corticosteroid-binding globulin levels was found, suggesting that the concentration of free, hormonally active corticosterone was increased. Antigenic challenge resulted in a significant rise of IL-1 production in a dose-related manner 2 h after immunization, except for the group given the highest dose of SRBC, which demonstrated strong elevation of serum corticosterone level by this time. However, IL-1 production by splenic macrophages, isolated at the peak of the hormonal reaction to SRBC (4 h after immunization), was suppressed in a dose-dependent fashion. An inverse relationship between endogenous levels of glucocorticoids and splenic plaque-forming cells number was also revealed. It is concluded that the interaction of IL-1 and glucocorticoids during the first hours after antigenic challenge is one of the factors controlling the magnitude of the immune response.

Serum corticosteroid-binding globulin levels in children undergoing heart surgery.

Serum corticosteroid-binding globulin (CBG) levels were measured in children (mean age 4 years) during heart surgery. Considerable decrease in CBG level occurred between baseline examination (416 +/- 39 nM) and the day of surgery (314 +/- 30 nM). Relatively simple closed heart surgery did not influence CBG level with maximal cortisol level being 20 +/- 4 micrograms/dl. Open heart surgery under conditions of profound hypothermia (26 C, without extracorporeal circulation) caused dramatic lowering of CBG level, particularly striking after resuscitation (180 +/- 20 nM). At the same time cortisol level reached extremely high values (78 +/- 8 micrograms/dl). These data suggest that CBG is likely to play an important role in pituitary-adrenal response to surgery under severe conditions of hypothermia and cardiac arrest.

Corticosteroid-binding globulin levels in the rat serum under conditions of starvation and restriction of motions.

Serum corticosteroid-binding globulin (CBG) concentrations were measured by a radioligand method in rats under the action of some factors influencing activity of pituitary-adrenal system. Basal CBG levels were about 2-fold higher in females than in males. In females only starvation resulted in a significant lowering of CBG activity, while in males CBG was affected only by restriction of motions for 5h Ether treatment in both sexes, pregnancy in females and adrenalectomy in males did not influence CBG levels.

On the role of corticosteroid-binding globulin (CBG) in modulating activity of glucocorticoids: developmental patterns for CBG, corticosterone, and a-fetoprotein levels in the rat serum.

The levels of corticosterone, corticosteroid-binding globulin (CBG), and a-fetoprotein (AFP) were measured in the serum of developing rats. It has been shown that the dramatic increase in CBG concentration and the decrease in AFP concentration of the same degree occur in males and females during the third postnatal week. The considerable rise in corticosterone level was observed only during 4th postnatal week. The data obtained in the study suggest that CBG may be responsible for the essential contribution to the developmental rise in glucocorticoid activity.

Interaction between cortisol and cortisol-binding protein in silver foxes (Vulpes fulvus).

1. Selection of silver foxes for domestic behaviour resulted in the parallel lowering of both cortisol and cortisol-binding protein (CBP) levels in the blood plasma. 2. During seasonal cycles (summer-winter) and after stress an increase in cortisol levels is followed by a decrease in CBP activity. 3. It is concluded that there are two types of interaction between cortisol and CBP in silver foxes: parallel changes in the process of domestication and opposite changes under the influence of environmental factors.

The study of properties of immunoreactive estradiol secreted by adrenals and ovaries of immature female rats.

Some properties of immunoreactive estradiol secreted by adrenals and ovaries of immature female rats were studied. It was shown that adrenals and ovaries of 15-day-old animals secrete approximately equal amounts of immunoreactive estradiol, with thin-layer chromatogram of immunoreactive material being identical for both glands. Adrenal- as well as ovarian-derived estradiol can bind to uterine cytosol estradiol receptors with the formation of complexes, which can be activated in the cell-free system. The removal of either adrenals or ovaries causes a decrease of cytosol estradiol receptor levels in the uterus 6 hours after the operation. From these results and previously reported data, nothing suggests that immunoreactive estradiol secreted by the adrenals of immature rats should be regarded as "spurious" hormone.

[Fast-dissociating complexes of estradiol and corticosterone with rat serum proteins]. / Bystrodissotsiiruiushchie kompleksy estradiola i kortikosterona s belkami syvorotki krovi krys.

The dissociation of estradiol complexes with specific binding proteins of blood sera from 5-day-old and pregnant rats was studied. Two types of complexes differing essentially in their dissociation rates were obtained. The decomposition of fast-dissociating complexes was completed within 30 s. Two classes of corticosterone-binding sites, one of which could form highly labile complexes, were revealed.

[Effect of cortisol on estradiol secretion and its reception in the morning and evening hours in 30-day-old female rats]. / Vliianie kortizola na sekretsiiu éstradiola i ego retseptsiiu v utrennie i vechernie chasy u samok krys v 30-sytochnom vozraste.

Cortisol administration (250 micrograms) to 5-day-old female rats was studied for its effect on the diurnal (morning-evening) rhythm of the estradiol secretion and reception on the 30th day of life. This stimulus had no influence on the estradiol level in the morning time. In the evening the estrogen concentration in the control group decreased while in the cortisol-treated group there were no changes. Disturbance of the circadian periodicity in the serum estradiol concentration in cortisol-treated animals was not induced by changes in the secretory ability of adrenals and ovaries, which was estimated by measurement of the estradiol production by glands in vitro. This disturbance was not a result of changes in hormone reception in uterine cytosol. The increased estradiol level in cortisol-treated rats in the evening is in good agreement with effects caused by neonatal glucocorticoid treatment in the reproductive system.

[Neonatal exposure to cortisol: disturbance of adrenal and reproductive system function in developing female rats]. / Neonatal'noe vozdeistvie kortizolom: Narushenie funktsii nadpochechnikov i polovoi sistemy u razvivaiushchikhsia.

A study was made of the effect of cortisol administration on the 5th day of postnatal life on the development of the sexual system and adrenal function in female rats. Neonatal treatment with cortisol at a dose of 250 micrograms was shown to cause delayed maturity and a decrease in sex receptivity. This treatment also caused a decrease in adrenal and ovarian secretion in vitro of corticosterone and progesterone by rats aged 30 days and a decrease in the blood level of corticosterone of maturing animals. It was assumed that sex developmental disorder was determined by chronic deficiency of blood corticosterone.

[Endocrine mechanisms of a delay in the onset of sexual maturity in female rats after neonatal exposure to cortisol]. / Endokrinnye mekhanizmy zaderzhki nastupleniia polovoi zrelosti u krys-samok posle neonatal'nogo vozdeistviia kortizolom.

A study was made of the effect of neonatal cortisol treatment on maturity development, ontogenesis of the secretion of estradiol by the endocrine glands and its reception in the uterine cytosol in female rats. This treatment caused a considerable delay of the vaginal opening and the onset of the first estrus. An increase in estradiol secretion by the adrenal glands was observed in maturing rats of the study group. Estradiol secretion by the ovaries was not greatly changed. Neonatal cortisol treatment did not influence the development of estradiol reception in the uterine cytosol either. It was assumed that sex developmental disturbance was associated with estradiol hypersecretion by the adrenal glands.

[Secretion of steroid hormones by the adrenals and ovaries and estradiol receptors in the uterine cytosol in postnatal ontogenesis]. / Sekretsiia steroidnykh gormonov nadpochechnikami i iaichnikami i retseptsiia éstradiola v tsitozole matki v postnatal'nom ontogeneze.

The authors presented the results of a comparative study of ontogenesis of progesterone and estradiol production by the adrenal glands and ovaries in rats (from the 8th to the 60th days of life). A parallel study was made of the formation of the estradiol receptor system of the uterus. Immature rats adrenal glands in vitro were shown to produce much more progesterone than the ovaries. Progesterone production in the adrenal glands correlated with the intensity of corticosterone secretion. At the prepubertal age (the 8th-30th days of life) the adrenal glands and ovaries produced approximately the same amounts of estrogens determined as estradiol by a radioimmunoassay. The development of the uterine receptor system demonstrated parallelism with ontogenesis of the adrenal estrogen secreting activity. Such a regularity was undetectable for the ovaries. The authors discussed possible influence of the adrenal glands on the concentration of estradiol receptors in the uterus by means of estrogen synthesized by these receptors and immunologically similar to estradiol.