Modulation of thyrotrophin release from an intracellular pool by pre-exposure to thyrotrophin-releasing hormone and dibutyryl cyclic AMP

Publisher Website
Google Scholar
Abstract
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 × 105/250 μl 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 μg/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 μg/l vs 3·98 ± 0·22); K+ response was reduced to 86% of the control (3·77 ± 0·21 μg/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. We suggest that an intracellular pool of TSH exists which can be depleted by prior TRH exposure without a desensitization effect. The size of this pool may be increased by dbcAMP, indicating that cyclic nucleotides may modulate the availability of TSH to an acutely releasable intracellular pool. J. Endocr. (1986) 108, 211–217

This publication has 14 references indexed in Scilit: