title: Bone morphogenetic protein 6 promotes FSH receptor and anti-Müllerian hormone mRNA expression in granulosa cells from hen prehierarchal follicles.
abstract: A growing body of literature provides evidence of a prominent role for bone morphogenetic proteins (BMPs) in regulating various stages of ovarian follicle development. Several actions for BMP6 have been previously reported in the hen ovary, yet only within postselection (preovulatory) follicles. The initial hypothesis tested herein is that BMP6 increases FSH receptor (FSHR) mRNA expression within the granulosa layer of prehierarchal (6-8 mm) follicles (6-8 GC). BMP6 mRNA is expressed at higher levels within undifferentiated (1-8 mm) follicles compared with selected (≥9 mm) follicles. Recombinant human (rh) BMP6 initiates SMAD1, 5, 8 signaling in cultured 6-8 GC and promotes FSHR mRNA expression in a dose-related fashion. In addition, a 21 h preculture with rhBMP6 followed by a 3 h challenge with FSH increases cAMP accumulation, STAR (StAR) expression, and progesterone production. Interestingly, rhBMP6 also increases expression of anti-Müllerian hormone (AMH) mRNA in cultured 6-8 GC. This related BMP family member has previously been implicated in negatively regulating FSH responsiveness during follicle development. Considering these data, we propose that among the paracrine and/or autocrine actions of BMP6 within prehierarchal follicles is the maintenance of both FSHR and AMH mRNA expression. We predict that before follicle selection, one action of AMH within granulosa cells from 6 to 8 mm follicles is to help suppress FSHR signaling and prevent premature granulosa cell differentiation. At the time of selection, we speculate that the yet undefined signal directly responsible for selection initiates FSH responsiveness. As a result, FSH signaling suppresses AMH expression and initiates the differentiation of granulosa within the selected follicle.
authors.affiliation: Center for Reproductive Biology and Health, The Pennsylvania State University, 227 Henning Building, University Park, Pennsylvania 16802, USA.
authors.forename: O M
authors.initials: OM
authors.lastname: Ocón-Grove
authors.forename: D H
authors.initials: DH
authors.lastname: Poole
authors.forename: A L
authors.initials: AL
authors.lastname: Johnson
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000235:genetics* / Q000378:metabolism; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D002645:Chickens / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009866:Oogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D055418:Bone Morphogenetic Protein 6; D012333:RNA, Messenger; D011962:Receptors, FSH; D011994:Recombinant Proteins; D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone