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.
ASJC Scopus subject areas