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Journal of Endocrinology (2008) 196, 251-261       DOI: 10.1677/JOE-07-0148
© 2008 Society for Endocrinology
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The activin receptor-like kinase 6 Booroola mutation enhances suppressive effects of bone morphogenetic protein 2 (BMP2), BMP4, BMP6 and growth and differentiation factor-9 on FSH release from ovine primary pituitary cell cultures

Julia M Young1,5, Jennifer L Juengel2, Kenneth G Dodds3, Mhairi Laird6, Peter K Dearden5, Alan S McNeilly6, Kenneth P McNatty4 and Theresa Wilson1

1 AgResearch Molecular Biology Unit, Department of Biochemistry, University of Otago, PO Box 56, Dunedin, New Zealand2 AgResearch, Wallaceville Animal Research Centre, Upper Hutt, New Zealand3 AgResearch Invermay Agricultural Centre, Mosgiel, New Zealand4 School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand5 Laboratory for Development and Evolution, Biochemistry Department, University of Otago, PO Box 56, Dunedin, New Zealand6 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

(Correspondence should be addressed to J M Young; Email: julia.young{at}agresearch.co.nz)

Bone morphogenetic proteins (BMPs) have been shown to influence the regulation of FSH synthesis and secretion at the level of the pituitary. Primary pituitary cells were harvested and cultured from Booroola ewes homozygous for a mutation in activin receptor-like kinase 6 (ALK6) also known as BMP receptor IB (BMPRIB), and from wild-type (WT) ewes to determine if the mutation caused alterations in FSH secretion in vitro. The cells were collected 24 h following induction of luteolysis and cultured for 72 h prior to being challenged for 24 h with BMP2, BMP4, BMP6, growth and differentiation factor-9 (GDF9), transforming growth factor-β 1, activin-A and GnRH. The levels of FSH and LH were measured by RIA and then compared with the untreated controls. Primary pituitary cell cultures from Booroola ewes secreted less FSH than WT cells in the presence of BMP2, BMP4 and BMP6. These BMPs did not affect the FSH stores within the cells, or the levels of LH released. GDF9 appeared to act in a BMP-like manner by suppressing FSH secretion. The ALK6 receptor however, was not found to co-localise with gonadotroph cells in either Booroola or WT pituitary tissues. These findings imply that the increased sensitivity of Booroola cells to BMP2, BMP4, BMP6 and GDF9 cannot be due to the direct action of the ALK6 mutant Booroola receptor in the cells that synthesise FSH.




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C. C. Ho and D. J. Bernard
Bone Morphogenetic Protein 2 Signals via BMPR1A to Regulate Murine Follicle-Stimulating Hormone Beta Subunit Transcription
Biol Reprod, July 1, 2009; 81(1): 133 - 141.
[Abstract] [Full Text] [PDF]




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