title: Gonadotrophin-responsiveness of granulosa cells from bone morphogenetic protein 15 heterozygous mutant sheep.
abstract: The aim of this study was to test the hypothesis that the higher ovulation-rate in ewes heterozygous for a mutation in bone morphogenetic protein 15 (BMP15; FecX(I); otherwise known as Inverdale or I+ ewes) is due to granulosa cells developing an earlier responsiveness to LH, but not FSH. To address this hypothesis, granulosa cells were recovered from every individual nonatretic antral follicle (>2.5 mm diameter) from I+ and wild-type (++) ewes during anoestrus and the luteal and follicular phases and tested for their responsiveness to FSH and human chorionic gonadotrophin (hCG; a surrogate for LH). For the FSH receptor (FSHR) binding study, granulosa cells were harvested in three separate batches from all antral follicles (> or = 2.5 mm diameter) from I+ and ++ ewes. Using a highly-purified ovine FSH preparation, no evidence was found to suggest that I+ ewes have a higher ovulation-rate due to enhanced sensitivity of granulosa cells to FSH with respect to cAMP responsiveness or to their FSHR binding characteristics (equilibrium K(d) or B(max)). By contrast, a significantly higher proportion of follicles from I+ ewes contained granulosa cells responsive to hCG. The higher proportion was due to cells from more small follicles (i.e. > 2.5-4.5 mm diameter) developing a response to hCG. It is concluded that the mutation in the BMP15 gene in I+ ewes leads to an earlier acquisition of LH responsiveness by granulosa cells in a greater proportion of follicles and this accounts for the small but significantly higher ovulation-rate in these animals.
authors.affiliation: Victoria University of Wellington, Wellington 6140, New Zealand. kenneth.mcnatty@vuw.ac.nz
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: McNatty
authors.forename: Derek A
authors.initials: DA
authors.lastname: Heath
authors.forename: Norma L
authors.initials: NL
authors.lastname: Hudson
authors.forename: Stan
authors.initials: S
authors.lastname: Lun
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Juengel
authors.forename: Lloyd G
authors.initials: LG
authors.lastname: Moore
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D055430:Bone Morphogenetic Protein 15 / Q000235:genetics* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D005838:Genotype; D006062:Gonadotropins / Q000494:pharmacology* / Q000502:physiology; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D012756:Sheep / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: D055430:Bone Morphogenetic Protein 15; D006062:Gonadotropins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP