EXPRESSION OF RYANODINE RECEPTORS IN THE PITUITARY-GLAND - EVIDENCE FOR A ROLE IRE GONADOTROPIN-RELEASING-HORMONE SIGNALING

GnRH elicits secretion of LW and FSH from gonadotropes by activating a n array of intracellular signals including the generation of inositol triphosphate and the release of intracellular calcium. Given the impor tant role of calcium in the secretory responses to GnRH, we examined t he expression and function of the ryanodine receptors, which are known to modulate calcium release from intracellular stores. Using RT-PCR a nalysis, we found that ryanodine receptor (RyR) types 2 and 3, but not type 1, are expressed in rat pituitaries. Pulses of GnRH were adminis tered to perifused primary rat pituitary cells in the presence or abse nce of a ryanodine receptor antagonist, ruthenium red, to assess effec ts on GnRH-mediatad LH secretion. Treatment with ruthenium red resulte d in a 40% decrease in the spike phase of GnRH-induced LH release and a 35% reduction in the pla teau phase. Ruthenium red also inhibited Gn RH-mediated transcription of a transfected alpha-LUC reporter plasmid. RyR messenger RNA (mRNA) expression varied duping the rat estrous cyc le with maximal levels following increases of progesterone. The effect s of gonadal steroids on pituitary RyR mRNA levels were examined direc tly in ovariectomized rats that were treated with estrogen (E), or est rogen and progesterone (P). In this paradigm, E decreased, whereas E P increased RyR3 mRNA levels. These results indicate that RyR is expr essed and hormonally regulated in the rat pituitary and suggest that i t might play a role in mediating GnRH-induced gonadotropin synthesis a nd secretion.