Functional growth hormone (GH) receptors and GH are expressed by preimplantation mouse embryos: A role for GH in early embryogenesis?

Abstract

The results of this study challenge the widely held view that growth hormone (GH) acts only during the postnatal period. RNA phenotyping shows transcripts for the GH receptor and GH-binding protein in mouse preimplantation embryos of all stages from fertilized eggs (day 1) to blastocysts (day 4). An antibody specific to the cytoplasmic region of the GH receptor revealed receptor protein expression, first in two-cell embryos, the stage of activation of the embryonic genome (day 2), and in all subsequent stages. In cleavage-stage embryos this immunoreactivity was localized mainly to the nucleus, but clear evidence of membrane labeling was apparent in blastocysts. GH receptor immunoreactivity was also observed in cumulus cells associated with unfertilized oocytes but not in the unfertilized oocytes. The blastocyst receptor was demonstrated to be functional, exhibiting the classic bell-shaped dose-response curves for GH stimulation of both 3-O-methyl glucose transport and protein synthesis. Maximal stimulation of 40-50% was seen for both responses at less than 1 ng͞ml recombinant GH, suggesting a role for maternal GH. However mRNA transcripts for GH were also detected from the morula stage (day 3) by using reverse transcription-PCR, and GH immunoreactivity was seen in blastocysts. These observations raise the possibility of a paracrine͞autocrine GH loop regulating embryonic development in its earliest stages.Embryonic and fetal growth have long been considered to be independent of pituitary growth hormone (GH). However, this view is challenged by a growing body of evidence which demonstrates a role for GH in the development of the fetus. Newborn Laron dwarfs, lacking a functional GH receptor, are more than 2 SD shorter than normal (1). Exogenous GH has been shown to restore embryonic growth in rats after transplantation of parts of embryos into hypophysectomized hosts (2). A number of fetal tissues has been shown to respond to GH in vitro (3-6). GH receptor transcripts have been demonstrated in day 12 rat embryos and placentae (7), day 51 sheep embryos (8), and mouse placenta (9). Immunoreactive GH receptor was observed in the human fetus from the second trimester (10, 11). Recently GH receptor transcripts and immunoreactivity have been demonstrated in germ-line competent mouse embryonic stem cells, and GH receptor transcripts were also demonstrated in mouse blastocysts (12).Preimplantation stages earlier than the blastocyst, however, were not examined by Ohlsson et al. (12). Furthermore, there was no evidence that these very early embryos were capable of receptor synthesis or of signal transduction after ligand binding to expressed receptor. In this study we demonstrate the presence of GH receptors in the early embryo from fertilization to the blastocyst stage and the ability of GH to influence the metabolism of blastocyst. Moreover, we report the expression of GH by preimplantation blastocysts, raising the possibility of paracrine͞autocrine regulation of embryonic growth by GH. MATERIALS AND METHODSGene Ex...

Extra-pituitary growth hormone in peripheral tissues of early chick embryos

“…It is therefore possible that extrapituitary GH may act as a local growth factor in early embryonic or fetal development. This possibility is supported by the recent demonstration of GH mRNA and GH immunoreactivity in murine blastocysts prior to implantation and cellular differentiation (Pantaleon et al 1997). It is, however, not known if GH is present in early embryonic tissues during embryogenesis or organogenesis.…”

“…It is therefore possible that GH acts as a local growth factor, as first suggested by Garcia-Aragon et al (1992) following their discovery of GHR in fetal rat tissues, prior to pituitary differentiation. This possibility is also supported by the ability of exogenous GH to induce glucose transport in pre-implantation mouse embryos, in which GH and GHR immunoreactivity and mRNA are found (Pantaleon et al 1997). Local GH actions are also thought to stimulate the development and hatching of mouse pre-implantation embryos (Drakakis et al 1995, Fukaya et al 1998.…”

“…Although Pantaleon et al (1997) demonstrated that non-maternal GH mRNA was present in pre-implantation mouse embryos prior to the formation of the morula, they did not determine if GH gene expression persisted during embryonic development, and Yang et al (1999) similarly found GH immunoreactivity and GH mRNA in trout embryos during gastrulation and organogenesis although they did not determine tissue distribution during ontogeny. The present results indicate that all tissues and most cells initially express the GH gene, although this capacity appears to be lost in some cells and some tissues (e.g.…”

Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution

“…Hormone and neurotransmitter receptors have also been found in oocytes and in female germline cells. For example, the oestrogen receptor (Wu et al 1992), serotonin receptor 5-HTID (Veselá et al 2003), Notch1 and Notch2 receptors (Cormier et al 2004), and the ␤2-andrenoceptor (Č ikoš et al 2005) have all been detected in oocytes, and the GH receptor has been detected in fertilized eggs (Pantaleon et al 1997;Kölle et al 2001). It is interesting to note that the changes in expression of some of the genes coding for these receptors coincide temporally with early waves of epigenetic re-programming during development.…”

Pregnancy and delivery after in vitro maturation of naked ICSI GV oocytes with GH and transfer of a frozen thawed blastocyst: case report

“…We recently found (1) that the GH receptor is present in the oocytes and the early pre-implantation human embryos, and that GH stimulates in vitro maturation of naked oocytes. Growth hormone receptor has been described in mouse, bovine oocytes and early pre-implantation embryos (2,3). GH has in vitro, a positive effect through an increase in cytoplasmic competence (5) leading to a better developmental capacity of the embryos.…”