EGF-Like Growth Factors As Mediators of LH Action in the Ovulatory Follicle

TLDR

LH triggers an inflammatory‑like cascade in the ovarian follicle, yet many of its effects are indirect because the LH receptor is expressed only in a subset of cells. LH induces transient sequential expression of amphiregulin, epiregulin, and beta‑cellulin, and these growth factors recapitulate LH‑induced cumulus expansion and oocyte maturation, acting as paracrine mediators that propagate the LH signal throughout the follicle.

Abstract

Before ovulation in mammals, a cascade of events resembling an inflammatory and/or tissue remodeling process is triggered by luteinizing hormone (LH) in the ovarian follicle. Many LH effects, however, are thought to be indirect because of the restricted expression of its receptor. Here, we demonstrate that LH stimulation induces the transient and sequential expression of the epidermal growth factor (EGF) family members amphiregulin, epiregulin, and beta-cellulin. Incubation of follicles with these growth factors recapitulates the morphological and biochemical events triggered by LH, including cumulus expansion and oocyte maturation. Thus, these EGF-related growth factors are paracrine mediators that propagate the LH signal throughout the follicle.