The ontogeny of hepatic growth hormone receptor and insulin-like growth factor I gene expression in the sheep fetus during late gestation: developmental regulation by cortisol.

Abstract

The effects of cortisol on hepatic GH receptor and insulin-like growth factor-I (IGF-I) gene expression were investigated in sheep fetuses during late gestation and after experimental manipulation of plasma cortisol levels by fetal adrenalectomy and exogenous infusion of cortisol. Hepatic GH receptor and IGF-I messenger RNA (mRNA) levels increased with increasing gestational age in parallel with the normal rise in fetal cortisol levels toward term (145 +/- 2 days). These increases in mRNA abundance toward term were prevented when the prepartum cortisol surge was abolished by fetal adrenalectomy and were stimulated prematurely in fetuses younger than 130 days by exogenous infusion of cortisol. Both the class 1 and class 2 transcripts of the IGF-I gene were increased when cortisol levels were elevated either endogenously or exogenously. However, there were no significant changes in fetal plasma IGF-I levels either with increasing gestational age or in response to experimental manipulation of the fetal cortisol level. When the data from all the fetuses were combined irrespective of treatment or gestational age, there were significant positive correlations between the log plasma cortisol concentration in utero and the abundance of GH receptor and IGF-I mRNA in the fetal liver. There was also a significant inverse relationship between log plasma cortisol and the ratio of class 1 to class 2 transcript abundance in the fetal liver. These findings show that cortisol is a physiological regulator of hepatic GH receptor and IGF-I gene expression in fetal sheep during late gestation and indicate that it preferentially increases the class 2 transcript of the IGF-I gene. The prepartum cortisol surge therefore appears to have an important maturational role in initiating the perinatal switch from the fetal to adult modes of somatotrophic regulation.

Ontogeny and nutritional manipulation of the hepatic prolactin–growth hormone–insulin-like growth factor axis in the ovine fetus and in neonate and juvenile sheep

“…2(b); Hyatt et al 2004c). Recent reports have suggested that there is a more sizeable increase in IGF-I abundance postnatally (Li et al 1996); the conflict in the data could be related to a variation in IGF-I transcripts detected. In our study, as a starting point, all IGF-I mRNA transcripts were amplified.…”

“…The onset of GH-dependent growth is simply understood to be the conversion from autocrine-paracrine control of growth, in which insulin and IGF-II are the major mitogens, to endocrine control, in which systemic growth is primarily under the influence of GH (Forhead et al 2000). The establishment of a GHresponsive endocrine system through an intact IGF network is thought to be crucial for successful adaptation from fetal to postnatal life (Li et al 1996).…”

Identification of Sp1 as the transcription factor for the alternative promoter P2 of the bovine growth hormone receptor gene

“…Although the 5 -UTR 1B initiated from P2 is ubiquitously expressed, GHR mRNA amounts in many tissues change in response to hormonal and physiological statuses (Harvey et al 1995, Bennett et al 1996, Florini et al 1996, Li et al 1996, Nguyen et al 1996, Chen et al 1997, Jux et al 1998. Changes in the total GHR mRNA may at least in part result from the changes in the activity of P2 because the GHR 1B mRNA represents the majority of the GHR mRNA pool.…”

Maternal nutrition alters the expression of insulin-like growth factors in fetal sheep liver and skeletal muscle

“…Radiolabelled antisense riboprobes were generated as previously described, corresponding to class 2 transcripts of the sheep IGF-I gene (exon 3 linked to the exon 2 promoter: Pell et al 1993, Li et al 1996, to exon 3 of the sheep IGF-II gene (Li et al 1993), and to the intracellular domain of the sheep GHR gene (Li et al 1996). The IGF-I riboprobe was designed so that when hybridised to total RNA, two bands were possible corresponding to the homologous mRNA transcript class (class 2 transcripts), as well as to any other IGF-I mRNA transcript class (class 1 transcripts), which hybridised to the region of the probe corresponding to exon 3 (Pell et al 1993, Li et al 1996. However, no class 2 transcripts of IGF-I were detected in Figure 1 Mean metabolisable energy (ME) intake for ewes nutrient restricted between days 28 and 80 of gestation and then well fed for the remainder of pregnancy () or well fed throughout pregnancy ().…”