Effect of Streptozotocin Diabetes on the Hypothalamic-Pituitary-Thyroid Axis in the Rat*

Abstract

Studies of the hypothalamic-pituitary-thyroid axis have been performed in streptozotocin (STZ)-diabetic Wistar rats and their controls. Plasma PBI concentration, plasma and pituitary TSH, contents, and hypothalamic TRH content were measured by RIA in basal and stimulated conditions. Compared to controls, rats made diabetic by 6.0 or 7.5 mg STZ/100 g BW showed decreased plasma PBI and TSH and diminished pituitary TSH content, with greater alterations in rats receiving the highest STZ dose. Both diabetic groups showed an almost 50% reduction of hypothalamic TRH content in comparison with the mean control value. After thyroidectomy, pituitary TSH secretion increased in diabetic, ad libitum fed, and semistarved animals, but it was lower in the diabetic group in which the reduction in plasma PBI was similar or greater. To evaluate pituitary sensitivity to the inhibitory action of L-T4 on TSH secretion in diabetes, thyroidectomized control (Thx-C), thyroidectomized diabetic (Thx-D), and thyroidectomized semistarved (Thx-S) rats were injected twice daily for 7 days with either saline or a fractional L-T4 dose of 0.25, 0.50, or 1.00 microgram/100 microgram/100 g BW. In Thx-D rats, a daily dose of 1.00 microgram L-T4 was sufficient to normalize pituitary TSH secretion, while a dose of 2.00 microgram was required to induce a similar effect in the Thx-C and Thx-S animals. Pituitary TSH content was increased in the Thx-C group with increasing T4 doses. No modification in this parameter was seen in the Thx-D and Thx-S animals. The fact that diabetes caused a reduction in the hypothalamic TRH content indicates that the primary cause of pituitary-thyroid alterations in STZ-diabetic rats lies in the hypothalamus, although the metabolic imbalance induced by diabetes and, in less degree, by undernutrition could also be partly responsible for some of the described modifications.

Pituitary-thyroid axis in short- and long-term experimental diabetes mellitus

“…Absolute thyroid and pituitary gland weights were unchanged in all 3 DM groups, in contrast to a significantly decreased thyroid or pituitary gland weight reported previously (17,18) for male Wistar rats 15 days after DM induction. This difference may be related to the different sex or strain of the animals studied.…”

“…Several investigators have reported decreased serum TSH as well as T 4 levels 10 to 30 days after DM induction (1)(2)(3)17,18). The decreased TSH has been ascribed to a diminished pituitary sensitivity to TRH (17,19) or to an intrinsic reduction in the constitutive and/or regulated TSH secretion by the diabetic thyrotropes (20).…”

Central neuropeptide Y infusion and melanocortin 4 receptor antagonism inhibit thyrotropic function by divergent pathways

“…In addition to glucocorticoids, the hypothalamo-pituitary-thyroid axis is regulated by insulin. Rats that were made insulin deficient by the administration of streptozotocin showed decreases in circulating levels of TSH, T3 and T4 as well as pituitary TSH and hypothalamic TRH content (Gonzalez et al, 1980 andMitsuma andNogimori, 1982). Thus, it is unlikely that the hyperinsulinemia observed after acute (this study) and chronic (Baran et al, 2002) ICV NPY but not HS014 administration in pair fed rats could contribute to the differences in effects on thyroid hormone concentrations presently observed, in keeping with the observation that insulin administration is unable to prevent the fasting-induced reduction in thyrotropic axis in rats .…”

“…Moreover, corticosterone and insulin status can have significant effects on thyroid hormone concentrations (Kakucska et al, 1995, Alkemade et al, 2005, Nicoloff et al, 1970, Gonzalez et al, 1980and Mitsuma and Nogimori, 1982. Therefore, in order to determine whether changes in insulin or corticosterone levels may have contributed to these changes in thyroid hormone concentrations, we investigated circulating insulin and corticosterone concentrations in NPYand HS014-injected rats.…”

“…Acute ICV NPY administration is known to modulate circulating concentrations of corticosterone and insulin (Sainsbury et al, 1996;Wisialowski et al, 2000), both of which -in addition to thyroid hormones -influence energy homoestasis. Moreover, corticosterone and insulin status can have significant effects on thyroid hormone concentrations (Kakucska et al, 1995;Alkemade et al, 2005;Nicoloff et al, 1970;Gonzalez et al, 1980;Mitsuma and Nogimori, 1982). Therefore, in order to determine whether changes in insulin or corticosterone levels may have contributed to these changes in thyroid hormone concentrations, we investigated circulating insulin and corticosterone concentrations in NPY-and uncoupling protein 3 (UCP-3) in this tissue was determined, since the expression and activity of UCP-3 is known to be regulated by thyroid function (Lanni et al, 2003;Flandin et al, 2009).…”