Abstract
The effects of mifepristone on basal and stimulated production of cyclic adenosine monophosphate (cAMP) and corticosteroid hormones (progesterone and corticosterone) have been studied in vitro using adrenal glands from control rats and rats with streptozotocin-induced diabetes. In adrenals of rats with streptozotocin diabetes, both basal and adrenocorticotropic hormone (ACTH) stimulated cAMP production were significantly increased; this was accompanied by an increase in basal and ACTH stimulated production of rat adrenal progesterone and corticosterone in vitro. Repeated administration of mifepristone to control and diabetic rats resulted in a preferential increase of the ACTH-stimulated production of corticosterone, the main glucocorticoid hormone, without additional changes in the level of cAMP production. These results suggest activation of two mechanisms responsible for increased steroidogenesis in experimental animals. In rats with streptozotocin diabetes, the increased formation of the second messenger mediating of ACTH action on adrenocortical cells, cAMP, increases both basal and ACTH-stimulated activity of all stages of steroidogenesis. After long-term administration of mifepristone to both control and diabetic rats activity of the later stages of steroidogenesis increases with a predominant increase in the synthesis of physiologically active hormone corticosterone without additional changes in the level of cAMP production.
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The experiments were carried out in accordance with the Rules of the Laboratory Practice Using Experimental Animals, approved by order of the Ministry of Public Health of the Russian Federation (no. 267 of June 19, 2003), and ethical principles established by the European Convention for the Protection of Vertebrate Animals Used for Experimental and other Scientific Purposes (1986).
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Selyatitskaya, V.G., Afonnikova, E.D., Pal’chikova, N.A. et al. Hypercorticism During Streptozotocin Diabetes and Mifepristone Administration: the Role of Cyclic Adenosine Monophosphate. Biochem. Moscow Suppl. Ser. B 14, 57–61 (2020). https://doi.org/10.1134/S1990750820010138
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DOI: https://doi.org/10.1134/S1990750820010138