Thyroid hormones regulate the expression of somatostatin receptor subtypes in the rat pituitary.
Circulating TSH levels are increased in hypothyroidism and suppressed in hyperthyroidism. On the other hand, the hypothalamic hormone somatostatin suppresses basal and TRH-induced TSH release, an effect which is enhanced by thyroid hormones. To investigate whether the effects of thyroid hormones on TSH secretion may be mediated in part through alterations in the gene expression of pituitary somatostatin receptors (SSTR), 3-week-old male Sprague-Dawley rats were rendered hypothyroid with antithyroid drugs for 3 weeks. Total RNA extracted from anterior pituitaries were analysed for SSTR mRNA levels, using Northern blot hybridization. Compared to controls, hypothyroid rats had significantly lower pituitary mRNA levels of SSTR1 and SSTR2 (p < 0.0001 for both, n = 16); the reductions could be prevented by T4 supplementation (3 microgram/100 g body weight/day i.p.). In vitro studies using GH4C1 rat pituitary cells showed that the addition of T3 10(-8) M to cells cultured in charcoal-stripped bovine calf serum resulted in significant increases in mRNA levels of SSTR1 (p < 0.0001; n = 7) and the two transcripts of SSTR2 (p < 0.0005; n = 7). The increase for SSTR1 showed no further increase with higher doses of T3, but was time-dependent and could be seen consistently after 8 h of incubation. We conclude that thyroid hormones regulate the gene expression of SSTR subtypes in the pituitary, via a direct action on anterior pituitary cells. Changes in SSTR gene expression may contribute to the increase in circulating TSH levels in hypothyroidism.
Lam
K S
KS
Department of Medicine, University of Hong Kong, Hong Kong, China. ksllam@hkucc.hku.hk
Wong
R L
RL
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013963:Thyroid Hormones / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013963:Thyroid Hormones; C101130:somatostatin receptor type 1; D013972:Thyrotropin; C093733:somatostatin receptor 2; D013974:Thyroxine