title: [The functional activity of thyroid of male rats with acute and mild streptozotocin diabetes].
abstract: The type 1 diabetes mellitus (DM1) and dysfunction of thyroid are the most common endocrine diseases, which are interrelated. However, the molecular mechanisms of thyroid dysfunction in DM1 and the role of adenylyl cyclase signaling system (ACSS) in this process remain poorly understood. Typically for studying etiology and pathogenesis of thyroid diseases in DM1 the models of acute DM1 induced by high doses of streptozotocin (STZ) are used. At the same time, a suitable model for this purpose is the model of mild DM1 induced by moderate doses of STZ, which more closely resembles human DM1. The aim of this work was a comparative study of the thyroid functional state in rats with 30-day acute DM1 induced by injection of STZ at a dose of 65 mg/kg, and in rats with the 30- and 210-day mild DM1 induced by three consecutive injections of STZ at medium doses (30-40 mg/kg). For this purpose in diabetic animals the levels of thyroid hormones and TSH and the functional activity of hormone-sensitive ACSS in membranes isolated from thyroid were studied. It was shown that in blood of rats with acute DM1 the levels of fT4, fT3 and tT3 were decreased by 45%, 23% and 19%, respectively, while the level of TSH did not changed significantly. In rats with 30-day mild DM1 the concentration of fT4 was decreased by 32%, while the levels of tT4, tT3 and TSH were similar to those in control. In rats with prolonged mild DM1 after 150 and 210 days after the first treatment with STZ the levels of tT4, fT4 and tT3 were significantly reduced, but the concentration of TSH in rats with 210-day mild DM1 was increased by 119%. The results obtained in the study of the thyroid status and TSH levels in rats with prolonged mild DM1 are in good agreement with the data obtained in the study of thyroid diseases in patients with DM1. It was found that the basal activity of adenylyl cyclase (AC) in the membranes isolated from thyroid of diabetic rats did not change, except for rats with prolonged mild DM1 where this activity was increased by 21%. In all groups of diabetic rats the decrease of AC stimulating effects of GppNHp (10(-5) M) and TSH (10(-8) M) was found, and in the rats with prolonged mild DM1 the AC effect of PACAP-38 (10(-6) M) was also reduced. The decrease of the AC effect of TSH varied among different groups of the diabetic animals: in the rats with acute DM1 this effect was reduced by 46% and in the rats with the 30- and 210-day mild DM1--by 18% and 34%. Thus, it was concluded that the key cause of thyroid resistance to TSH under conditions of DM1 is a weakening of the signal transduction generated by TSH via the ACSS.
authors.forename: I V
authors.initials: IV
authors.lastname: Moyseyuk
authors.forename: K V
authors.initials: KV
authors.lastname: Derkach
authors.forename: A O
authors.initials: AO
authors.lastname: Shpakov
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000378:metabolism* / Q000503:physiopathology; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood
chemical_list: D013963:Thyroid Hormones; D013972:Thyrotropin; D000262:Adenylyl Cyclases