Subacute thyroiditis follows an unpredictable clinical course that is hardly affected by its clinical features or treatment.

No abstract

Neuropeptide-Y (NPY) is a 36-amino acid C-terminally amidated peptide found within the hypothalamus that can potently stimulate carbohydrate feeding. Moreover, the hypothalamic content of NPY can be modulated by peripheral hetabolic status. To further evaluate the regulation of NPY synthesis in states of altered metabolic homeostasis, we measured the hypothalamic content of prepro-NPY mRNA in streptozocin (STZ)-diabetic, STZ-diabetic insulin-replaced, and control rats by both nuclease protection and in situ hybridization analyses. Adult male Sprague-Dawley rats received a single injection of STZ (100 mg/kg, ip) or citric acid (control). Beginning 72 h later one group of STZ-treated animals received daily injections of insulin (4 U Ultralente/day). All animals were killed 17-19 days after STZ or control treatment. STZ-treated animals were hyperglycernic and showed growth failure compared to control rats. Glycemic control was restored by insulin replacement, as was partial growth. Nuclease protection analysis revealed an approximately 3- to 4-fold increase in prepro-NPY mRNA levels in the samples from STZ-treated rats vs. control. This increase was returned to control values by insulin replacement. In situ hybridization analysis revealed the STZ-induced increase in hypothalamic prepro-NPY mRNA was detectable in the arcuate nucleus at levels that were in agreement with the nuclease protection results, but that NPY expression in other brain regions appeared to be either unaffected or decreased after STZ treatment. These data suggest that hypothalamic NPY expression is modulated by peripheral metabolic status and provide further explanation for the hyperphagia accompanying STZ-induced diabetes.

Diabetes mellitus in the rat is associated with loss of pulsatile GH secretion. An interplay between hypothalamic GH-releasing factor (GRF) and inhibitory factor [somatostatin (SRIF)] secretion is thought to account for episodic pituitary GH release. An increase in SRIF tone/action or a decrease in GRF release/response in diabetic rats could account for the suppressed GH levels. Pituitaries from streptozotocin-diabetic rats contained less GH than controls (15.9 +/- 2.5 vs. 29.5 +/- 4.6 micrograms/mg; P less than 0.05) despite normal somatotrope representation, as demonstrated using immunofluorescence studies. Basal GH secretion from monolayer culture of dispersed anterior pituitary (AP) cells from diabetic rats was proportionately decreased (150 +/- 10 vs. 103 +/- 10 ng/10(5) cells; P less than 0.005). GRF (10(-11)-10(-8) M)-induced release of GH from AP cells was decreased in diabetic rats (maximum response to 10(-8) M GRF, 401 +/- 60 vs. 618 +/- 41 ng/10(5) cells; P less than 0.01); however, sensitivity to GRF was unchanged (EC50, 79 +/- 41 vs. 128 +/- 67 pM). By contrast, SRIF (10(-7)-10(-10)-induced inhibition of GRF (10(-8) M)-mediated GH release was impaired in AP cells of diabetic rats compared to that in controls (IC50, 112 +/- 33 vs. 55 +/- 31 pM; P less than 0.05) associated with a decrease in AP plasma membrane SRIF receptor concentration (63.4 +/- 15.6 vs. 160.3 +/- 13.7 fmol/mg protein; P less than 0.05), with no change in affinity. These findings are consistent with chronic exposure to increased hypothalamic SRIF influence. GH synthesis has been shown to be independent of SRIF regulation; however, insulin-like growth factor-I and GRF inhibit and stimulate GH synthesis, respectively. In diabetic rats insulin-like growth factor-I levels were decreased, appropriate to low GH status, in serum (290 +/- 66 vs. 1662 +/- 92 ng/ml; P less than 0.001) and hypothalamus (6.8 +/- 1.0 vs. 13.0 +/- 0.4 pg/mg wet wt; P less than 0.001) and, thus, did not seem to account for the low AP GH content. Hypothalamic GRF content in diabetic rats (1.11 +/- 0.10 ng/hypothalamus) did not differ from that in controls (1.16 +/- 0.17 ng/hypothalamus). GRF mRNA levels, however, were reduced by 80% in diabetic rats compared to controls. Taken together these data support a combined role for decreased hypothalamic GRF and increased SRIF in mediating alterations of GH synthesis and secretion in streptozotocin-induced diabetes.