Sustained treatment with a GnRH agonist (leuprorelin) affects the ultrastructural characteristics of membranous organelles in male rat pituitary gonadotropes

Abstract

Summary. Gonadotropin-releasing hormone agonists exert acutely stimulatory action on gonadotropes, but thereafter suppress paradoxically gonadotropin synthesis and release by receptor desensitization. To examine whether GnRH signaling affects the morphological characteristics in membranous organelles related to the synthesis of gonadotropin, we have analyzed the ultrastructural changes in the ER and Golgi apparatus of male rat pituitary gonadotropes during sustained treatment with a GnRH agonist, leuprorelin. In pituitary gonadotropes at 1 day after the onset of treatment, clusters of the tubuloreticular ER appeared, and the globular Golgi apparatus was transiently disassembled into isolated small-sized stacks. However, 1 week after the onset of the treatment, the tubuloreticular ER was seemingly converted to rough ER with regularly stacked sheets and the scattered Golgi stacks converged to form globular structures. In the following chronic phase of the treatment, the ER cisterns remained flattened and the trans-Golgi compartment appeared to be collapsed. Sustained treatment with leuprorelin could also restore the enlarged Golgi apparatus and expand the cisterns of the rough ER; a feature that was seen in hypertrophic gonadotropes of castrated rats. These findings indicated that the ultrastructure of the membranous organelles changed because of the chronic suppressive effects of leuprorelin on gonadotropes both in the physiological and stimulated states. The acute and chronic ultrastructural changes in the ER and Golgi apparatus during sustained leuprorelin treatment also suggests that GnRH signaling cross-talks with the regulation of the morphological characteristics in membranous organelles related to gonadotropin synthesis. generating secretory granules, in this study we have investigated the temporal changes in the ultrastructure of the ER and Golgi apparatus in pituitary gonadotropes of male rats receiving 1-month depot formulation of leuprorelin. Based on the findings, we will discuss the putative crosstalk between GnRH signaling and the regulation of the structural properties of the ER and Golgi apparatus within gonadotropes.