Estradiol regulates gonadotropin-releasing hormone receptor number, growth and inositol phosphate production in alpha T3-1 cells.
Gonadal steroids act at the pituitary to regulate gonadotropin-releasing hormone (GnRH) receptor number and the responsiveness of gonadotropes to GnRH and can act at post-receptor sites to modulate Ca(2+)-mediated and protein kinase C-mediated signal-transducing pathways. However, such effects have been seen in the mixed cell population of primary cell cultures and may involve indirect effects on cells other than gonadotropes. Here, steroid effects on a recently described gonadotrope-derived cell line (alpha T3-1 cells) have been assessed. In these cells estradiol, progesterone, testosterone and corticosterone all exerted trophic effects. Estradiol increased [3H]thymidine incorporation with an EC50 of 10(-12) to 10(-11) M and this effect was blocked by keoxifene, an estrogen receptor antagonist. Estradiol also reduced binding of [125I]buserelin (EC50 approximately 10(-11) M), an effect which appears to reflect a reduction in GnRH receptor number rather than a change in Kd. Estradiol also shifted the dose-response curve for GnRH-stimulated inositol phosphate (IP) accumulation rightward, increasing the EC50 for this GnRH effect by approximately 20-fold. Accordingly estradiol acts directly upon alpha T3-1 cells not only to reduce GnRH receptor number, but also to reduce the efficiency of coupling of residual GnRH receptors to second messenger generation.
McArdle
C A
CA
Institute for Hormone and Fertility Research, University of Hamburg, Germany.
Schomerus
E
E
Gröner
I
I
Poch
A
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003345:Corticosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000096:biosynthesis*; D010880:Piperidines / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D020849:Raloxifene Hydrochloride; D051381:Rats; D011966:Receptors, LHRH / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D007295:Inositol Phosphates; D010880:Piperidines; D011966:Receptors, LHRH; D013739:Testosterone; D020849:Raloxifene Hydrochloride; D011374:Progesterone; D004958:Estradiol; D003345:Corticosterone