Modulation of thyrotrophin release from an intracellular pool by pre-exposure to thyrotrophin-releasing hormone and dibutyryl cyclic AMP.
Amplification of desensitization of TSH response to thyrotrophin-releasing hormone (TRH) may be important mechanisms in the regulation of its secretion. We have investigated this possibility in vitro, using monolayer culture of rat anterior pituitary cells. Cells (1-1.5 X 10(5)/250 microliters per well) were cultured for 72 h, exposed to TRH or dibutyryl cyclic AMP (dbcAMP) for 6 or 8 h, washed, and then treated for 4 h with various doses of TRH, or with K+ (55 mmol/l) as a non-specific secretagogue. Pretreatment with TRH (20 nmol/l) for 8 h reduced subsequent TSH release: basal release fell to 64% of the control value (1.01 +/- 0.10 micrograms/l pretreated, 1.58 +/- 0.16 control) and release in response to TRH (100 nmol/l) to 69% of the control (2.7 +/- 0.19 micrograms/l vs 3.98 +/- 0.22); K+ response was reduced to 86% of the control (3.77 +/- 0.21 micrograms/l vs 4.39 +/- 0.20), significantly less than the other reductions. The extent of the parallel downward shift of the TRH dose-response curve was proportional to dose and duration of prior TRH exposure. There was no significant change in the dose of TRH required to cause half-maximal TSH release (ED50: pretreated 4.8, control 2.8 nmol TRH/l) suggesting depletion of an intracellular pool of TSH rather than 'desensitization'. After 6-h pretreatment with dbcAMP, subsequent TSH responses were augmented: basal release was 130% of the control, response to TRH (100 nmol/l) was 137% and to K+ it was 132% of the control, with a parallel upward shift of the TRH dose-response curve but no change in cellular TSH content.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D007424:Intracellular Fluid / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D013973:Thyrotropin-Releasing Hormone; D003994:Bucladesine; D013972:Thyrotropin