GH(3) CELLS TRANSFECTED WITH GONADOTROPIN-RELEASING-HORMONE (GNRH) RECEPTOR COMPLEMENTARY DEOXYRIBONUCLEIC-ACID RELEASE SECRETOGRANIN-II THROUGH A CONSTITUTIVE PATHWAY AFTER GNRH ANALOG-REGULATED SYNTHESIS - EVIDENCE THAT SECRETORY PROTEINS DO NOT CONTAIN A SEQUENCE THAT OBLIGATES PROCESSING THROUGH A SECRETORY GRANULE OR BY REGULATED SECRETION

GGH(3) cells (lactotropic GH(3) cells transfected with rat GnRH recept or complementary DNA) respond to GnRH agonists with time- and dose-dep endent release of secretogranin-II (SII), a molecule believed to be a marker of the regulated pathway of release and a component of secretor y granules. Release requires both protein and RNA synthesis and is als o stimulated by analogs of the cyclic nucleotides. Release, as such, a ppears to be determined by the availability of SII, because this proce ss is constitutive once the molecule is synthesized, and intracellular levels are at the same steady state whether the receptor is occupied by an agonist or an antagonist or is unoccupied. This synthetic requir ement is consistent with the lag in time from stimulation to release a nd the inhibitory actions of either cycloheximide or actinomycin-D on secretion as well as the morphologic observation that storage granules (i.e, secretory granules) are absent in these cells. SII, accordingly , can be released constitutively and does not require processing throu gh the so-called regulated secretory pathway. These observations sugge st, in addition, that proteins associated with release through regulat ed pathways do not have ''sorting'' domains that preclude release via constitutive routes or require processing through secretory granules.