title: Possible role of corticosterone in the down-regulation of the hypothalamo-hypophysial-thyroid axis in streptozotocin-induced diabetes mellitus in rats.
abstract: We investigated the effects of diabetes mellitus on the hypothalamo-hypophysial-thyroid axis in male (R x U) F1 and R-Amsterdam rats, which were found to respond to streptozotocin (STZ)-induced diabetes mellitus with no or marked increases, respectively, in plasma corticosterone. Males received STZ (65 mg/kg i.v.) or vehicle, and were killed 1, 2 or 3 weeks later. At all times studied, STZ-induced diabetes mellitus resulted in reduced plasma TSH, thyroxine (T4) and 3,5,3'-tri-iodothyronine (T3). Since the dialyzable T4 fraction increased after STZ, probably as a result of decreased T4-binding prealbumin, plasma free T4 was not altered during diabetes. In contrast, both free T3 and its dialyzable fraction decreased during diabetes, which was associated with an increase in T4-binding globulin. Hepatic activity of type I deiodinase decreased and T4 UDP-glucuronyltransferase increased after STZ treatment. Thus, the lowered plasma T3 during diabetes may be due to decreased hepatic T4 to T3 conversion. Median eminence content of TRH increased after STZ, suggesting that hypothalamic TRH release is reduced during diabetes and that this is not caused by impaired synthesis or axonal transport of TRH to the median eminence. Hypothalamic proTRH mRNA did not change in diabetic (R x U) F1 rats during the period of observation, but was lower in R-Amsterdam rats 3 weeks after STZ. Similarly, pituitary TSH and TSH beta mRNA had decreased in R-Amsterdam rats by 1 week after STZ treatment, but did not change in (R x U) F1 rats. The difference between the responses in diabetic R-Amsterdam and (R x U) F1 rats may be explained on the basis of plasma corticosterone levels which increased in R-Amsterdam rats only. Hypothalamic TRH content was not affected by diabetes mellitus, but the hypothalami of diabetic rats released less TRH in vitro than those of control rats. Moreover, insulin had a positive effect on TRH release in vitro. In conclusion, the reduced hypothalamic TRH release during diabetes is probably not caused by decreases in TRH synthesis or transport to the median eminence, but seems to be due to impaired TRH release from the median eminence which may be related to the lack of insulin. Inhibition of proTRH and TSH beta gene expression in diabetic R-Amsterdam rats is not a primary event but appears to be secondary to enhanced adrenal activity in these animals during diabetes.
authors.affiliation: Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands.
authors.forename: G A
authors.initials: GA
authors.lastname: van Haasteren
authors.forename: E
authors.initials: E
authors.lastname: Sleddens-Linkels
authors.forename: H
authors.initials: H
authors.lastname: van Toor
authors.forename: W
authors.initials: W
authors.lastname: Klootwijk
authors.forename: F H
authors.initials: FH
authors.lastname: de Jong
authors.forename: T J
authors.initials: TJ
authors.lastname: Visser
authors.forename: W J
authors.initials: WJ
authors.lastname: de Greef
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008473:Median Eminence / Q000378:metabolism; D009924:Organ Culture Techniques; D010902:Pituitary Gland / Q000378:metabolism; D011355:Prodrugs / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D011355:Prodrugs; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D007453:Iodide Peroxidase; D013974:Thyroxine; D003345:Corticosterone