Bone loss in ovariectomized rats: dominant role for estrogen but apparently not for FSH.
We have shown previously that, in sheep primary pituitary cells, bone morphogenetic proteins (BMP)-4 inhibits FSHb mRNA expression and FSH release. In contrast, in mouse LbT2 gonadotrophs, others have shown a stimulatory effect of BMPs on basal or activin-stimulated FSHb promoter-driven transcription. As a species comparison with our previous results, we used LbT2 cells to investigate the effects of BMP-4 on gonadotrophin mRNA and secretion modulated by activin and GnRH. BMP-4 alone had no effect on FSH production, but enhanced the activinCGnRH-induced stimulation of FSHb mRNA and FSH secretion, without any effect on follistatin mRNA. BMP-4 reduced LHb mRNA up-regulation in response to GnRH (Gactivin) and decreased GnRH receptor expression, which would favour FSH, rather than LH, synthesis and secretion. In contrast to sheep pituitary gonadotrophs, which express only BMP receptor types IA (BMPRIA) and II (BMPRII), LbT2 This is an Open Access article distributed under the terms of the Society for Endo distribution, and reproduction in any medium, provided the original work is prop Journal of Endocrinology (2008) 196, 497–507 0022–0795/08/0196–497 q 2008 Society for Endocrinology Printed in Great cells also express BMPRIB. Smad1/5 phosphorylation induced by BMP-4, indicating activation of BMP signalling, was the same whether BMP-4 was used alone or combined with activinGGnRH. We hypothesized that activin and/or GnRH pathways may be modulated by BMP-4, but neither the activin-stimulated phosphorylation of Smad2/3 nor the GnRH-induced ERK1/2 or cAMP response elementbinding phosphorylation were modified. However, the GnRH-induced activation of p38 MAPK was decreased by BMP-4. This was associated with increased FSHb mRNA levels and FSH secretion, but decreased LHb mRNA levels. These results confirm 1. BMPs as important modulators of activin and/or GnRH-stimulated gonadotrophin synthesis and release and 2. important species differences in these effects, which could relate to differences in BMP receptor expression in gonadotrophs. Journal of Endocrinology (2008) 196, 497–507