Testosterone Stimulates Follicle-Stimulating Hormone (beta) Transcription via Activation of Extracellular SignalRegulated Kinase: Evidence in Rat Pituitary Cells

This study investigated whether estradiol (E2) or testosterone (T) activate extracellular signal-regulated kinase (ERK) and calcium/calmodulin-dependent kinase II (Ca/CaMK II), as indicated by enzyme phosphorylation in rat pituitaries. In vivo studies used adult female rats given E2, T, or empty silastic capsules (vehicle controls). Twenty-four hours later, the rats were given a single pulse of GnRH (300 ng) or BSA-saline (to controls) and killed 5 min later. GnRH stimulated a two- to three-fold rise in activated Ca/CaMK II, and E2 and T had no effect on Ca/CaMK II activation. In contrast, both GnRH and T stimulated threefold increases in ERK activity, with additive effects seen following the combination of GnRH+T. E2 had no effect on ERK activity. In (alpha)T3 cells. In vitro studies with cultured rat pituitary cells examined the effect of GnRH±T in the presence of the mitogen-activated protein (MAP) kinase kinase inhibitor, PD-098059 (PD). Results showed that PD suppressed ERK activational and FSH? transcriptional responses to T. These findings suggest that one site of T regulation of FSH(beta) transcription is through the selective stimulation of the ERK pathway.