Testosterone stimulates follicle-stimulating hormone beta transcription via activation of extracellular signal-regulated 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 clonal gonadotrope cells, dihydrotestosterone did not activate ERK alone but enhanced and prolonged the ERK responses to GnRH, demonstrating direct effects on the gonadotrope. Thus, the ERK response to GnRH plus androgen was enhanced in both rat pituitary and 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 beta 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.
Haisenleder
D J
DJ
Division of Endocrinology and Metabolism, Department of Medicine, and the Center for Research in Reproduction, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA. djh2q@virginia.edu
Burger
L L
LL
Aylor
K W
KW
Dalkin
A C
AC
Walsh
H E
HE
Shupnik
M A
MA
Marshall
J C
JC
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D004958:Estradiol / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology; D010052:Ovariectomy; D010766:Phosphorylation; D010902:Pituitary Gland / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D013739:Testosterone / Q000502:physiology*; D015533:Transcriptional Activation
D037201:Follicle Stimulating Hormone, beta Subunit; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases