The paraventricular nucleus of the hypothalamus has a major role in thyroid hormone feedback regulation of thyrotropin synthesis and secretion

T. Taylor, F. E. Wondisford, T. Blaine, B. D. Weintraub, T. Taylor

Research output: Contribution to journalArticle

Abstract

The role of the hypothalamic paraventricular nucleus (PVN) in thyroid hormone regulation of TSH synthesis during hypothyroidism was studied in adult male rats that were normal (n = 10), had primary hypothyroidism with sham lesions in the hypothalamus (n = 17), and had primary hypothyroidism with PVN lesions (n = 14). Two and 4 weeks after initiation of treatment, plasma levels of thyroid hormones (TSH, corticos-terone and PRL) and pituitary content of TSHβ and α-subunit mRNA were measured. TRH mRNA levels in the PVN were determined by in situ hybridization histochemistry. At 2 weeks, despite a decrease in plasma free T4 in both hypothyroid groups, plasma TSH levels increased, but to a lesser degree, in the hypothyroid PVN lesioned compared to hypothyroid sham-lesioned group (7.8 ± 1.3 vs. 20.5 ± 1.1 ng/dl; P < 0. 05). Similarly, at 4 weeks, the hypothyroid PVN-lesioned group demonstrated a blunted TSH response compared to the hypothyroid sham-lesioned group (6.8 ± 0.7 vs. 24.0 ± 1.3 ng/dl; P < 0.05). Plasma corticosterone and PRL did not significantly differ between sham-lesioned and PVN-lesioned groups. TSHβ mRNA levels markedly increased in hypothyroid sham-lesioned rats compared to those in euthyroid controls at 2 weeks (476 ± 21% vs. 100 ± 39%; P < 0.05) and 4 weeks (1680 ± 270% vs. 100 ± 35%; P < 0.05). In contrast, TSHβ mRNA levels did not increase with hypothyroidism in the PVN-lesioned group compared to those in euthyroid controls at 2 weeks (140 ± 16%, P = NS) and only partially increased at 4 weeks (507 ± 135; P < 0.05). a mRNA levels at 4 weeks markedly increased in hypothyroid sham-lesioned rats compared to those in euthyroid controls (1121 ± 226% vs. 100 ± 48%; P < 0.05), but did not increase in the hypothyroid PVN-lesioned rats (61 ± 15%; P - NS). TRH mRNA in the PVN increased in the hypothyroid sham-lesioned rats compared to those in euthyroid controls (16.6 ± 1.3 vs. 4.8 ± 1.2 arbitrary densitometric units; P < 0.05), and TRH mRNA was not detectable in the PVN of hypothyroid- lesioned rats at 2 weeks. In summary, lesions in rat PVN prevented the full increase in plasma TSH, pituitary TSHβ mRNA, and α mRNA levels in response to hypothyroidism. Thus, factors in the PVN are important in thyroid hormone feedback regulation of both TSH synthesis and secretion.

Original languageEnglish (US)
Pages (from-to)317-324
Number of pages8
JournalEndocrinology
Volume126
Issue number1
DOIs
StatePublished - Jan 1990

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ASJC Scopus subject areas

  • Endocrinology

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