Actions of 17β-Estradiol on Gonadotropin Release Induced by Drugs That Activate Intracellular Signal Transduction Mechanisms in Rat Anterior Pituitary Cells1

Abstract

We studied the effects of 17 beta-estradiol (E2) on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release induced by drugs that activate different intracellular signal transduction mechanisms in rat anterior pituitary cells. Cells were pretreated with E2 (6 x 10(-10) M) or diluent for 24 h. Then, both E2- and diluent-pretreated cells were incubated for 4 h with E2 or diluent, respectively, with or without drugs, and in the presence or absence of gonadotropin-releasing hormone (GnRH). Media were assayed for LH and FSH by radioimmunoassays. E2 treatment had no effect on basal FSH release, but occasionally stimulated basal LH release. Phospholipase C (PLC), L-alpha-1,2-dioctanoyl glycerol (C8), veratridine, 8-bromo-cyclic adenosine 3',5'-monophosphate (8-Br-cAMP), melittin (a phospholipase A2 [PLA2] activator), arachidonic acid, PLA2, and GnRH all stimulated LH and FSH release in both E2- and diluent-treated cells. E2 treatment increased both LH and FSH release induced by GnRH, PLC, C8, veratridine, and 8-Br-cAMP, but not by melittin, arachidonic acid, and PLA2. Neither C8, PLA2, nor arachidonic acid in combination with a maximal dose of GnRH had additive effects on either LH or FSH release, whereas melittin increased the maximal response to GnRH in both E2- and diluent-treated cells. The effects of veratridine and 8-Br-cAMP depended on dose of GnRH and presence or absence of E2. These results suggest that E2 augments stimulus-coupled gonadotropin release by interacting with the Ca2+-, and/or diacylglycerol-, and cAMP-activated pathways, but not with the arachidonic acid-activated pathway.