The hepatocyte growth factor system as a regulator of female and male gonadal function

Abstract

The hepatocyte growth factor (HGF) system comprises HGF, its receptor (the c-met tyrosine kinase), HGF activator (HGFA) protein, and HGFA inhibitor (HAI). The components of the HGF system have been identified in a plethora of tissues to include the ovary and testis. In its traditional context, the HGF system works via paracrine-and autocrine-mediated feedback in which HGF (of mesenchymal origin) binds and activates c-met (within epithelial cells); target cells then respond to HGF via any number of morphogenic and functional changes. The concomitant presence of HGFA and HAI suggests that HGF bioactivity can be locally modulated. A number of studies have collectively shown that the mammalian ovary and testis contain HGF, c-met, and HGFA; very little is currently known regarding HAI within the gonad. Within the ovary, HGF controls numerous key functions which collectively regulate the growth and differentiation of ovarian follicles; these include cell growth, steroidogenesis, and apoptosis within theca cells and/or granulosa cells. Comparatively, less is known about the function of HGF within the testicular Leydig and Sertoli cells, but evidence is emerging that HGF may regulate somatic cell function, including Leydig cell steroidogenesis. Changes in the cellular origin of HGF and c-met during fetal and postnatal testicular development suggest that HGF, in collaboration with other growth factors, may regulate important aspects of testicular cell morphogenesis and differentiation which enable male sexual viability. Likewise, experimental evidence showing that HGF can modulate many vital processes which enable ovarian follicle growth, differentiation, and function indicate the importance of HGF in female reproduction. This review presents what is currently known regarding the expression of the HGF system and its function within the ovary and testis.

Global gene expression in granulosa cells of growing, plateau and atretic dominant follicles in cattle

“…It also stimulates bovine granulosa cell proliferation in vitro [55] and has anti-apoptotic effects on rat granulosa cells in vitro [56]. It has been suggested that HGF controls theca cell and granulosa cell steroidogenesis [57], indicating an important role during folliculogenesis. HGF is an upstream regulator predicted to be downregulated in our contrast P vs A, which is consistent with the proliferative and anti-apoptotic effect of that molecule on granulosa cells.…”

Hepatocyte Growth Factor Is a Mouse Fetal Leydig Cell Terminal Differentiation Factor1

“…The C-MET/HGF system has a well-established morphogenetic role in the embryonic development of mouse male gonads [43,[50][51][52][53]. In addition, an increasing amount of evidence demonstrates the implication of the C-MET/HGF HGF IS A FLC TERMINAL DIFFERENTIATION FACTOR system in the physiology of postnatal male and female reproductive organs as well as in the regulation of their differentiation [43][44][45]. The present study extends previous findings by our group focusing on the role of C-MET/HGF system in late embryonic development and in Leydig cells that are the main targets of HGF signals at this developmental stage [53].…”

“…The hepatocyte growth factor (HGF) is a pleiotropic cytokine and a well-known regulator of mouse embryonic morphogenesis [43]. Moreover, the contribution of the C-MET/ HGF system in the regulation of the physiology of postnatal testis and ovary is well known [44][45][46][47][48][49].…”

Effects of Endocrine-disrupting Chemicals on Female Reproductive Health

“…An important criterion (among several) for the selection is that the follicle secretes high levels of estradiol. Local growth factors such as insulin-like growth factors (IGFs), activins, transforming growth factor (TGF) α and β , hepatocyte growth factor, and FGF7 are also required for this process [65].…”