Altered thyrotropin (TSH) carbohydrate structures in hypothalamic hypothyroidism created by paraventricular nuclear lesions are corrected by in vivo TSH-releasing hormone administration.
TSH is a glycoprotein hormone composed of two subunits with attached carbohydrate chains that have varying structural characteristics. To determine the role of TRH in vivo in regulating structural characteristics of TSH carbohydrate chains, adult rats received paraventricular nuclear (PVN) lesions (n = 6) or sham lesions (n = 6). The PVN contain large amounts of TRH, and rats with lesions in these hypothalamic nuclei have been shown to have decreased plasma thyroid hormone levels. At 10 days after surgery, sc osmotic pumps infusing saline or 1 mg/kg/day TRH were placed. At 14 days after surgery, pituitaries were removed and incubated with [3H]glucosamine for 24 h. Glycopeptides prepared from secreted TSH were sequentially eluted from Concanavalin-A chromatography columns selecting unbound, weakly bound, and strongly bound forms. Plasma free T4 was lower in the PVN lesioned rats treated with saline than sham lesioned rats treated with saline (1.6 +/- 0.4 vs. 5.2 +/- 0.1 ng/dl, P less than 0.001). In vivo TRH administration in the PVN lesioned group normalized plasma free T4 but had no effect on free T4 in the sham group. Secreted TSH glycopeptides in the PVN lesioned rats treated with saline as compared to sham lesioned rats treated with saline had fewer unbound forms reflecting multiantennary structures (43 +/- 4 vs. 57 +/- 1%; P less than 0.05) and more weakly bound forms reflecting biantennary structures (50 +/- 4 vs. 35 +/- 2%; P less than 0.05). TRH administration in vivo normalized the Concanavalin-A binding pattern of secreted TSH glycopeptides in the PVN lesioned group but had no significant effect in the sham lesioned group. TSH alpha-subunit demonstrated both multi- and biantennary forms but TSH-beta subunit showed a predominance of multiantennary forms in both the PVN and sham lesioned groups treated with saline. In vivo changes in TRH levels altered TSH carbohydrate characteristics as described above for both subunits. In summary, hypothalamic hypothyroidism altered TSH carbohydrate structures, and in vivo TRH administration normalized these structures in parallel with the correction of serum free T4. In addition to reported quantitative changes in TSH in response to TRH, these qualitative changes may have an important effect on TSH action.
Taylor
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Molecular, Cellular, and Nutritional Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Weintraub
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BD
D000818:Animals; D002241:Carbohydrates; D055598:Chemical Phenomena; D002621:Chemistry; D007031:Hypothalamus / Q000502:physiology*; D007037:Hypothyroidism / Q000378:metabolism*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D002241:Carbohydrates; D013963:Thyroid Hormones; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin