Sequential effects of follicle-stimulating hormone and luteinizing hormone on mouse cumulus expansion in vitro

LH and FSH play critical roles in the development and function of the cumulus oophorus of the mammalian follicle, but the significance of cumulus LH receptors and the nature of the functional interaction between LH and FSH in relation to the process of cumulus expansion are not well understood. Controversy may arise from contradictory results of cumulus LH receptor assays, possibly as a consequence of relative sensitivities of the assays utilized, limited availability of tissue of specific developmental stages, or limitations on the access of radiolabeled ligands to cumulus LH receptors in the intact follicle. It has also been difficult to understand the basis for the apparent difference in gonadotropin requirements for cumulus expansion in vitro and in vivo; FSH seems to be required for expansion in vitro and LH initiates expansion in vivo. In this study, we show that expansion of mouse cumulus-oocyte complexes (COCs) in vitro occurs to a degree comparable to that seen in vivo when COCs are challenged with highly purified FSH (hpFSH) and highly purified LH (hpLH) together or when treatment with hpFSH precedes treatment with LH. Saturation radioreceptor assays revealed that FSH up-regulates cumulus cell LH receptors in the absence of LH and that LH may stimulate expansion upon binding to these acutely formed receptors. A model of cumulus expansion describing effects of both FSH and LH in vivo is proposed.