In mammalian ovarian follicles, follicle stimulating hormone (FSH) and luteinizing hormone (LH) signal primarily through the G-protein G_s to elevate cAMP, but both of these hormones can also elevate Ca²⁺ under some conditions. Here, we investigate FSH- and LH-induced Ca²⁺ signaling in intact follicles of mice expressing genetically encoded Ca²⁺ sensors, Twitch-2B and GCaMP6s. At a physiological concentration (1 nM), FSH elevates Ca²⁺ within the granulosa cells of preantral and antral follicles. The Ca²⁺ rise begins several minutes after FSH application, peaks at ∼10 min, remains above baseline for another ∼10 min, and depends on extracellular Ca²⁺. However, suppression of the FSH-induced Ca²⁺ increase by reducing extracellular Ca²⁺ does not inhibit FSH-induced phosphorylation of MAP kinase, estradiol production, or the acquisition of LH responsiveness. Like FSH, LH also increases Ca²⁺, when applied to preovulatory follicles. At a physiological concentration (10 nM), LH elicits Ca²⁺ oscillations in a subset of cells in the outer mural granulosa layer. These oscillations continue for at least 6 h and depend on the activity of G_q family G-proteins. Suppression of the oscillations by G_q inhibition does not inhibit meiotic resumption, but does delay the time to 50% ovulation by about 3 h. In summary, both FSH and LH increase Ca²⁺ in the granulosa cells of intact follicles, but the functions of these Ca²⁺ rises are only starting to be identified.

Summary Sentence

Both FSH and LH increase Ca²⁺ in the granulosa cells of intact ovarian follicles from mice expressing genetically encoded sensors.