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

We have studied the effects of trifluoperazine, a proposed inhibitor of calmodulin directed cellular function, on adrenocorticotrophic hormone (ACTH), thyroid stimulating hormone (TSH), prolactin (Prl) and growth hormone (GH) secretion from primary cultures of rat adenohypophyseal cells. 5 X 10(-6)M and 10(-5)M trifluoperazine caused a significant (P less than 0.005) reversible dose-related decrease in basal Prl secretion but was less effective on basal GH secretion, significant reversible inhibition (P less than 0.005) occurring only with 10(-5)M. Trifluoperazine did not consistently alter basal ACTH or TSH secretion but did inhibit 10(-2)M theophylline stimulation of ACTH, Prl and GH secretion and 1.5 X 10(-7)M TRH stimulation of TSH and Prl secretion. Paradoxically 10(-5)M trifluoperazine enhanced theophylline stimulation of TSH secretion. Our results show trifluoperazine to have differential effects on Prl, GH, ACTH and TSH secretion, which are consistent with the known calcium dependence of pituitary hormone secretion and may suggest a role for calmodulin in this process.