The oocyte-secreted factors bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) regulate folliculogenesis, oocyte quality and fecundity. They are comprised of a pro-domain and a mature domain and it is known the pro-proteins are biologically active on cumulus cells. In addition, there is evidence that GDF9 and BMP15 can form a potent heterodimer called cumulin. This study utilized various recombinant forms of GDF9, BMP15 and cumulin to assess the effect of; 1) homo- versus hetero-dimer proteins and, 2) pro-mature versus mature forms of proteins, on primary human granulosa-lutein cell function. Cells were treated in vitro with GDF9, BMP15, or cumulin ± their pro-domains; mRNA expression and protein secretion of inhibin A and B and activin B were measured. Regardless of whether cells were treated with mature- or pro-forms, GDF9 or BMP15 alone exhibited minimal effects on inhibin/activin production, whereas the addition of both factors elicited a marked synergistic increase in INHβB mRNA and protein production of inhibin B and activin B, but not inhibin A. Consistent with the hypothesis GDF9-BMP15 synergism is due to the actions of cumulin, both mature cumulin and pro-cumulin dose-dependently increased INHβB mRNA expression and inhibin B and activin B production, but not inhibin A. FSH induced expression of INHα mRNA expression leading to a 2- to 3-fold increase in inhibin B production when co-treated with GDF9+BMP15 or cumulin, and a corresponding decrease in activin B production. In general proteins in the pro-form and those lacking the pro-domain elicited the same effect on inhibin/ activin production, suggesting that the pro-domain may have a minimal role in the actions of these growth factors on granulosa cells. In conclusion, oocyte-secreted GDF9 and BMP15, likely in the form of the heterodimer cumulin, exert paracrine control of gonadotrophin-induced production of inhibin B/activin B in follicular granulosa cells.