Follicle-stimulating hormone regulates expression and activity of epidermal growth factor receptor in the murine ovarian follicle
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Authors: El-Hayek, Stephany; Demeestere, Isabelle; Clarke, Hugh J.
Abstract
Fertility depends on the precise coordination of multiple events within the ovarian follicle to ensure ovulation of a fertilizable egg. FSH promotes late follicular development, including expression of luteinizing hormone (LH) receptor by the granulosa cells. Expression of its receptor permits the subsequent LH surge to trigger the release of ligands that activate EGF receptors (EGFR) on the granulosa, thereby initiating the ovulatory events. Here we identify a previously unknown role for FSH in this signaling cascade. We show that follicles of Fshb(-/-) mice, which cannot produce FSH, have a severely impaired ability to support two essential EGFR-regulated events: expansion of the cumulus granulosa cell layer that encloses the oocyte and meiotic maturation of the oocyte. These defects are not caused by an inability of Fshb(-/-) oocytes to produce essential oocyte-secreted factors or of Fshb(-/-) cumulus cells to respond. In contrast, although expression of both Egfr and EGFR increases during late folliculogenesis in Fshb(+/-) females, these increases fail to occur in Fshb(-/-) females. Remarkably, supplying a single dose of exogenous FSH activity to Fshb(-/-) females is sufficient to increase Egfr and EGFR expression and to restore EGFR-dependent cumulus expansion and oocyte maturation. These studies show that FSH induces an increase in EGFR expression during late folliculogenesis and provide evidence that the FSH-dependent increase is necessary for EGFR physiological function. Our results demonstrate an unanticipated role for FSH in establishing the signaling axis that coordinates ovulatory events and may contribute to the diagnosis and treatment of some types of human infertility.
Gonadotropin characterization, localization and expression in the European hake (Merluccius merluccius)
REPRODUCTION
Authors: Candelma, Michela; Fontaine, Romain; Colella, Sabrina; Santojanni, Alberto; Weltzien, Finn-Arne; Carnevali, Oliana
Abstract
In vertebrates, the regulation of gametogenesis is under the control of gonadotropins (Gth), follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh). In fish, the physiological role of Gths is not fully understood, especially in species with asynchronous ovarian development. To elucidate the role of Gths in species with asynchronous ovary, we studied European hake (Merluccius merluccius) during the reproductive season. For this aim, we first cloned and sequenced both hormones. Then, we characterized their amino acid sequence and performed phylogenetic analyses to verify the relationship to their orthologues in other species. In addition, the quantification of gene expression during their natural reproductive season was analyzed in wild-caught female hake. Our results revealed that fshb peaked during the vitellogenic phase, remaining high until spawning. This is in contrast to the situation in species with synchronous ovary. lhb, on the other hand, peaked during maturation as it is also common in species with synchronous ovarian development. Finally, combining double-labeling fluorescent in situ hybridization (FISH) for Gth mRNAs with immunofluorescence for Lh protein, we evidenced the specific expression of fshb and lhb in different cells within the proximal pars distalis (PPD) of the pituitary. In addition to gonadotrope cells specific to expression of either fshb or lhb, some cells showed co-expression of both genes. This suggests either that gonadotropes with co-expression are not yet specified or they could have a plasticity that permits changes from one cell phenotype to another during certain life stages and in turn during different physiological states.