Studies on the role of calcium and cyclic nucleotides in the control of TSH secretion

Thyrotropin-releasing Hormone Stimulation of Prolactin Release from Clonal Rat Pituitary Cells

“…This finding for TRH action is consistent with the hypothesis (4) that Ca2+ is the coupling factor between stimiilus and secretion. Indirect evidence in support of the contention that TRH may act by affecting cellular Ca2+ metabolism comes from studies demonstrating that TRH enhances 45Ca2+ efflux both from rat anterior pituitary cells in vitro (5,6) and from GH3 cells, a clonal strain of rat pituitary cells that produce prolactin (7,8 be due to mobilization of Ca21 from an intracellular pool (or pools), to enhanced entry of Ca2+ from the extracellular environment, or to both. A series of recent electrophysiological stuidies using GH3 cells (9)(10)(11)(12) and primary mixed cultures of normal rat anterior pittuitary cells (13) have demonstrated that TRH also causes an increase in the frequency of Ca2+-dependent action potentials, and it has been suggested that Ca2+ traversing the plasma membrane duiring action potentials may be involved in hormone secretion.…”

Flunarizine, a calcium influx blocker, inhibits TRH- but not potassium-stimulated prolactin secretion

“…These results indicate that TRH-stimulated prolactin secretion probably involves calcium influx and that flunarizine may be useful as a probe for particular Ca2+ channels. There is considerable evidence that the release of adenohypophysial hormones is Ca2+-dependent. Manipulations which increase cytosolic Ca2+ (such as incubation of cells with high potassium concen¬ trations or calcium ionophores) increase secretion of hormone (Schrey et al 1978;Naor et al 1980;Thorner et al 1980;Gershengorn 1982). Spon¬ taneous Ca2+-dependent action potentials have been recorded in both normal and prolactin-secreting tumour pituitary cells.…”

Effects of trifluoperazine on rat prolactin, growth hormone, thyroid stimulating hormone and adrenocorticotrophin secretion in vitro

“…This enhancement of theophylline sti¬ mulation of TSH is unlikely to result from a selective lysis of TSH-secreting cells by trifluopera¬ zine, since basal levels of TSH secretion were unaltered by 10~5M trifluoperazine; and after ex¬ posure to trifluoperazine, levels of secretion in drug treated cultures were similar to those of control, untreated cultures. It is possible that tri¬ fluoperazine augmentation of theophylline may result from a direct action on adenylate cyclase (an effect which becomes overt only with simultaneous phosphodiesterase inhibition), since the phenothiazine, chlorpromazine, can stimulate anterior pituitary adenylate cyclase (Heindel & ClementCormier 1981); TSH secretion in response to the phosphodiesterase inhibitor, isobutylmethylxanthine is enhanced in the absence of extracellular calcium (Schrey et al 1978); and trifluoperazine also can potentiate 8-bromo-adenosine-3',5'-cyclic phosphate induced TSH release (Fleckman et al 1981). …”