| First Author | Zhou X | Year | 2016 |
| Journal | J Endocrinol | Volume | 229 |
| Issue | 3 | Pages | 331-41 |
| PubMed ID | 27029473 | Mgi Jnum | J:294378 |
| Mgi Id | MGI:6456502 | Doi | 10.1530/JOE-16-0053 |
| Citation | Zhou X, et al. (2016) Normal gonadotropin production and fertility in gonadotrope-specific Bmpr1a knockout mice. J Endocrinol 229(3):331-41 |
| abstractText | Pituitary follicle-stimulating hormone (FSH) synthesis is regulated by transforming growth factorbetasuperfamily ligands, most notably the activins and inhibins. Bone morphogenetic proteins (BMPs) also regulate FSHbeta subunit (Fshb) expression in immortalized murine gonadotrope-like LbetaT2 cells and in primary murine or ovine primary pituitary cultures. BMP2 signals preferentially via the BMP type I receptor, BMPR1A, to stimulate murine Fshb transcription in vitro Here, we used a Cre-lox approach to assess BMPR1A's role in FSH synthesis in mice in vivo Gonadotrope-specific Bmpr1a knockout animals developed normally and had reproductive organ weights comparable with those of controls. Knockouts were fertile, with normal serum gonadotropins and pituitary gonadotropin subunit mRNA expression. Cre-mediated recombination of the floxed Bmpr1a allele was efficient and specific, as indicated by PCR analysis of diverse tissues and isolated gonadotrope cells. Furthermore, BMP2 stimulation of inhibitor of DNA binding 3 expression was impaired in gonadotropes isolated from Bmpr1a knockout mice, confirming the loss of functional receptor protein in these cells. Treatment of purified gonadotropes with small-molecule inhibitors of BMPR1A (and the related receptors BMPR1B and ACVR1) suppressed Fshb mRNA expression, suggesting that an autocrine BMP-like molecule might regulate FSH synthesis. However, deletion of Bmpr1a and Acvr1 in cultured pituitary cells did not alter Fshb expression, indicating that the inhibitors had off-target effects. In sum, BMPs or related ligands acting via BMPR1A or ACVR1 are unlikely to play direct physiological roles in FSH synthesis by murine gonadotrope cells. |
