TSH REBOUND PHENOMENON IN THE RAT ADENOHYPOPHYSIS1

Abstract

The dynamics of pituitary TSH secretion have been studied in the female rat throughout prolonged goitrogencsis (3 weeks to one year) and during readjustment of the pituitary-thyroid system after removal of the goitrogenic stimulus (2–21 days). TSH levels in sera of rats 5–15 months old are relatively constant but hormone concentration in the adenohypophysis is more variable and falls substantially in the old animal. With chronic PTU treatment, blood thyrotrophin levels increase 70-300% and pituitary hormonal stores decrease to less than 5% of normal. Goitrogen withdrawal results in heightened accumulation of hormone stores in the pituitary (4–8 fold increase) with peak of rebound at 6–12 days. TSH rebound in the adenohypophysis is associated with return of AF-positive glycoprotein granulation in the thyroidectomy cell. Blood TSH titers during pituitary repletion remain at nearly normal levels. Doses of triiodothyronine and thyroxine which normally induce almost complete disappearance of thyrotrophin from blood and hypophysis are relatively ineffective in preventing the TSH rebound phenomenon in goitrous rats. The rebound effect is not induced in normal rats 10 days after cessation of thyroid hormone treatment. A “differential threshold” hypothesis of thyroid hormone function is proposed to explain the asynchronism in the dynamics of TSH secretion after goitrogen withdrawal. It is postulated that the momentum of TSH hypersecretion in the pituitary temporarily “overshoots” despite release from PTU and that the synthetic and storage phases are abnormally sensitive at this time to the low level of thyroid hormone produced by the unblocked gland. With subsequent rise in circulating levels of thyroid hormone, production and release of TSH are brought into balance and a steady state is re-established. Further increase in thyroid hormone to excessive levels inhibits both synthesis and release of thyrotrophin by the adenohypophysis.