Thyrotropin releasing hormone. A review of the mechanisms of acute stimulation of pituitary hormone release.

Abstract

Thyrotropin releasing hormone (TRH) acutely stimulates release of thyrotropin (TSH) and prolactin from anterior pituitary cells. A considerable number of studies have been performed with neoplastic and nonneoplastic pituitary cells in culture to elucidate the sequence of intracellular events involved in this action. Although cyclic AMP was suggested as an intracellular messenger, it has been demonstrated that TRH stimulation of hormone release can be dissociated from changes in cyclic AMP concentration, thereby supporting the contention that cyclic AMP is not a required mediator. In contrast, stimulation of hormone release by TRH requires Ca2+ and it seems likely that Ca2+ is the intracellular coupling factor between TRH stimulation and hormone secretion. TRH has been shown to stimulate 45Ca2+ efflux from preloaded pituitary cells. Enhanced 45Ca2+ efflux is thought to reflect an increase in the free intracellular Ca2+ concentration which leads to hormone release; however, the source of this Ca2− is uncertain. Results are reviewed from a series of experiments in pituitary cells which attempt to determine the pool (or pools) of Ca2+ that is affected by TRH. These include the following: the effects of decreasing the extracellular Ca2− concentration on hormone release stimulated by TRH; the effect of TRH on cellular Ca2+ as monitored by chlortetracycline; the effects of TRH on Ca2+ influx; the effects of the organic Ca2+ channel blocking agents, verapamil and methoxyverapamil, on TRH-stimulated hormone release; and the effects of TRH on plasma membrane potential difference and on Ca2+-dependent action potentials. Based on these data, separate hypotheses of the early events in TRH stimulation of hormone release in mammotropes and thyrotropes are proposed. In mammotropes, TRH is thought to stimulate prolactin release optimally by elevating the free intracellular Cat+ concentration by mobilizing cellular Ca2− only. In contrast, in thyrotropes under normal physiological conditions, TRH is thought to stimulate TSH release by mobilizing Ca2 from a cellular pool (or pools) and to augment this effect by also inducing influx of extracellular Ca2+ through voltage-dependent channels in the plasma membrane.