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The effect of immunocortin, an ACTH-like decapeptide VKKPGSSVKV corresponding to the 11-20 sequence of the variable part of the human IgG1 heavy chain on the content of 11-hydroxycorticosteroids (CS) in rat adrenal glands and blood serum in vivo was studied. An intramuscular injection of immunocortin at a dose of 10 microg/kg was found in an hour to induce a twofold decrease in CS content in the adrenal glands and a 1.8-fold increase in the blood serum CS content. At the same time, an immunocortin dose of 100 microg/kg exerted practically no effect on the CS content and its dose of 1000 microg/kg increased the CS content both in adrenal glands and in blood serum by 1.6 and 2.2 times, respectively. Four hours after the injection of any of the three doses of immunocortin, the CS content in adrenal glands did not differ from the control value, and after 24 h the content decreased threefold. Immunocortin was shown to be bound by the ACTH receptors in the membranes of the rat adrenal cortex with a high affinity and specificity (inhibiting the specific binding of 125I-labeled ACTH-(11-24) peptide with Ki of 1.2 nM).

Neonatal administration of hydrocortisone decrease steroidogenesis in the rat adrenals in immature and mature animals production of progesterone and androstenedione reducing, at that. Primary long-term disturbance of central regulatory influences controlling steroidogenesis in adrenals, was proposed. The steroid production disturbance in the gonads was lesser than in the adrenals and was found only in mature rats.

Biochemical and morphometric analyses have been made of the effects of nonapeptide neurohormones, vasotocin and mesotocin, on the chromaffin tissue of the adrenal gland of the frog, both in vivo and in vitro experiments. It was shown that vasotocin exerts stimulating effect on the suprarenal gland whereas mesotocin inhibits the latter. In vitro experiments revealed that adrenalin may abolish the effect of nonapeptides on the suprarenal gland.

Morphometric studies indicate that vasotocin increases the activity of the adrenal gland in frogs, whereas mesotocin and epinephrine do not essentially affect it. Combination of epinephrine with nonapeptides in cultural medium showed that the former may abolish the effect of vasotocin on the adrenal gland.

Studies of adenohypophyseal hormones, cortisol, T3, T4, thyroxine-binding globulin, testosterone, progesterone and estradiol in 90 neurotic men, treated or not with amitriptyline and benzodiazepines, allowed a conclusion that in the majority of them, endocrine functions were activated. 11 healthy men and 11 male patients underwent the three-day test with sinacten-depot (1 mg intramuscularly). The functional test data were compared over time by the methods of nonparametric statistics. The patients manifested a decrease of reserve potentialities of the pituitary-adrenal system, redistribution of the fractions of thyroid hormones, gonadotropins, the progesterone/estradiol ratio, a rise of prolactin and testosterone secretion. The drugs were found to improve the functioning of the pituitary-adrenal system. However, they did not contribute much to the positive changes in the pituitary-thyroid and other systems.

Unilateral lesions of septal region, which partially included commissure anterior, commissural nuclei, fornix and apical parts of medial and lateral preoptic area, inhibited hypothalamic self-stimulation in rabbits. Intraventricular injection of ACTH (4-10) and ACTH (1-24) evoked the restoration of self-stimulation behaviour.

The effect of repeated administration of a prolonged ACTH agent on the secretion of glucocorticoids, dehydroepiandrosterone (DEA) and delta 4- and delta 5-precursors was studied in experiments on male hamadryas baboons. The administration of Sinacten-depot at a dose of 1 mg for 5 days caused a noticeable decrease in the basal levels of cortisol, 11-deoxycortisol, pregnenolone, 17-oxypregnenolone, and DEA. Response of the adrenal glands to additional ACTH stimulation against a background of lowered basal indicators was completely preserved and increased 2-3-fold for pregnenolone, 17-oxypregnenolone and DEA. The amplitude of a maximum increment of cortisol in response to stress before and after ACTH treatment did not differ significantly, and for DEA it increased three times. Immobilization stress after preliminary ACTH treatment caused a stable increase in the level of DEA during stress factor action as well as 3 days after drug action.

Possible hormonal activity of ACTH4-7, a long-acting ACTH4-10 analog (ProGly Pro) was studied. Unlike ACTH5-10 the peptide did not reveal steroidogenic and melanocyte-stimulating activity.

The influence of ACTH (200 micrograms/kg), corticosterone (20 mg/kg) and cortexolone (20 mg/kg) on the anxiolytic activity of diazepam was studied. ACTH partly and corticosterone completely blocked the action of diazepam. Cortexolone injection 30 min before the administration of diazepam induced a 100% anxiolytic effect of diazepam in the range of doses from 0.1 to 0.3 mg/kg (ED50 of anxiolytic diazepam effect is 0.2 mg/kg). The role of stress hormones in the regulation of psychotropic drug activity is discussed.

Serum corticotropin and cortisol levels were measured in 20-40-year old healthy residents (144 males and 361 females) in the North. A functional Synacthen Depot test was performed in 5 volunteers. The adrenal glands from 56 males and 8 females of the same age who had died from accidents were pathohistologically and stereometrically examined. The signs of functional tension were established in the pituitary-adrenal cortex system. The Synacthen Depot test determined sufficient potentials of the organ to show responses to specific stimulation. Morphologically, a number of changes were found, which might be regarded as a prerequisite to the development of functional and pathological disturbances in the above-mentioned link of the endocrine system.

Submicroscopic changes in the adrenal cortex in dynamics of stress reaction development following preliminary corticotropin injection are characterized by less pronounced variations in quantitative parameters of basic structural components of parenchyma and stroma and are combined with stabilization of the 11-HCS level in blood and phasic effacement of general adaptogenic syndrome. The adaptogenic effect of the preparation at the organism level is observed with an accompanying increase in the adrenal cortex resistance to the influence of extreme factors.

Fragments of the adrenocorticotropic hormone ACTH1-24 and ACTH5-7 facilitate memory in the beetle T. molitor, the effect being observed at different stages after learning. An analogue of ACTH5-7 which contains D-phenylalamine, as well as D-phen7-ACTH4-7, inhibit memorization (the results checked 1 day after learning) and induce some other disturbances in the behaviour of beetles. To the 10th day of learning, the effects of the analogues cannot be distinguished from those of L-Phe7-fragments. The results obtained are compared with the known effect of ACTH fragments on memory in vertebrates.