Amiodarone and thyroid hormone effects on anterior pituitary hormone gene expression.
Amiodarone therapy results in marked changes in circulating thyroid hormone and TSH concentrations in man. In the present study we have demonstrated that amiodarone treatment of the rat increases serum TSH and pituitary cytoplasmic concentrations of TSH beta and alpha subunit messenger RNAs (mRNAs) and reduces PRL mRNA as measured by cytoplasmic dot hybridization with specific complementary (c) DNA probes. The fall in circulating TSH and TSH mRNA resulting from thyroid hormone treatment was less marked in animals receiving amiodarone in addition to T3 and T4. In contrast, in the hypothyroid state, increases in serum TSH, TSH beta and alpha mRNA, and reductions in PRL and GH mRNA were less marked in rats treated with amiodarone. In studies of rat anterior pituitary cells in primary monolayer culture we demonstrated a direct effect of amiodarone on PRL gene expression which was antagonized by T3. Changes in circulating thyroid hormone concentrations and deiodination of T4 and T3 induced by amiodarone in vivo may be important in the regulation of pituitary hormone gene expression but we have, in addition, shown a direct interaction between amiodarone and T3 effects on the anterior pituitary cell.
Franklyn
J A
JA
Department of Endocrinology, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, UK.
Gammage
M D
MD
Sheppard
M C
MC
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005796:Genes / Q000187:drug effects*; D007037:Hypothyroidism / Q000503:physiopathology; D010903:Pituitary Gland, Anterior / Q000187:drug effects; D010908:Pituitary Hormones, Anterior / Q000235:genetics*; D011388:Prolactin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013974:Thyroxine / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*
D010908:Pituitary Hormones, Anterior; D012333:RNA, Messenger; D014284:Triiodothyronine; D011388:Prolactin; D000638:Amiodarone; D013974:Thyroxine