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1 UMR 6175 INRA-CNRS-Université de TOURS-Haras Nationaux, Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France
1 Medical Research Council, Human Reproductive Sciences Unit, Centre for Reproductive Biology, The University of Edinburgh Chancellor’s Building, 49 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SB, UK
(Requests for offprints should be addressed to C Taragnat; Email: taragnat{at}tours.inra.fr)
Activins and inhibins, members of the transforming growth factor-beta family are able to stimulate and inhibit, respectively, FSH synthesis and release. Other members of this superfamily, the bone morphogenetic proteins (BMPs), may also affect FSH synthesis in the mouse. The aim of this work was to determine whether BMPs are expressed in the ovine pituitary and whether they play a role in the regulation of FSH release.
The mRNAs encoding BMP-2, BMP-4, BMP-7 and the oocyte-derived growth factor, growth differentiation factor (GDF)-9 were detected in the pituitaries of cyclic ewes by reverse-transcriptase PCR, as well as the mRNAs encoding the BMP type I receptors, BMPR-IA (activin-receptor-like kinase (ALK)-3) and BMPR-IB (ALK-6), and type II receptors (BMPR-II). Immunolabeling of pituitary sections revealed the presence of BMPR-IA (ALK-3) and BMPR-II in gonadotrope cells. To investigate the potential effects of BMPs on FSH secretion, ewe pituitary cell cultures were treated with BMP-4 (10–11 M to 10–9 M) for 48 h. Interestingly, FSH release was decreased in a dose-dependent manner. At 10–9 M BMP-4 both FSH concentration and FSHß mRNA expression were reduced by 40% of control values. In contrast, there was no inhibitory effect on either LH or LHß mRNA expression. A similar result was found with BMP-6. BMP-4 triggered the phosphorylation of Smad1, suggesting that the effect of BMP-4 on FSH secretion is due to the activation of the BMPs signaling pathway. Furthermore, BMP-4 blocked the stimulatory effect of activin on both FSH release and FSHß mRNA and amplified the suppression of FSH release and FSHß mRNA levels induced by 17ß-estradiol. These results indicate that a functional BMP system operates within the sheep pituitary, at least in vitro, to decrease FSH release and to modulate the effect of activin.
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