Reproductive and metabolic endocrinology of Romney rams selected for high or low circulating IGF-I concentrations
Introduction
Insulin-like growth factor-1 (IGF-1) is a mitotic polypeptide (Svoboda et al., 1980) that stimulates lactate synthesis (Oonk and Grootegoed, 1998), glucose transport (Oonk et al., 1989) and cell proliferation (Borland et al., 1984). In females, IGF-1 plays an important role in the control of growth and reproduction and influences the metabolism, cell division, ovarian folliculogenesis, oogenesis and ovarian secretory activity (Gong, 2002). Likewise, in the male, it affects germ cell development and the maturation of sperm (Neuvians et al., 2005).
IGF-1 is mainly produced by the liver under the control of growth hormone (GH) (Clemmons and Underwood, 1991) and acts on target tissues as a hormone (Borland et al., 1984). However, it also acts via the paracrine routes, in which IGF-I is produced locally in tissues, and is regulated independently of GH (Holly, 2004, Frago and Chowen, 2005). The insulin-like growth factor system consists of two ligands (IGF-1 and IGF-2), Type 1 and Type 2 IGF receptors, IGF-binding proteins (“IGFBP's”), and IGFBP proteases (Froesch et al., 1985).
IGF-I production in testicular tissue has been confirmed by the expression of IGF-I mRNA in the whole testis (Casella et al., 1987), production of IGF-I from Sertoli cells in culture (Cailleau et al., 1990) and localization by in situ hybridization and immuno-histochemistry (Hansson et al., 1989). In addition, the IGF Type 1 receptor (IGF-1R) has also been found in the Sertoli and the Leydig cells, and in secondary spermatocytes and spermatids (Handelsman et al., 1985). IGF-1 synthesis in the Sertoli cells is locally stimulated by follicle stimulating hormone by FSH (Cailleau et al., 1990), whilst IGF-I stimulates basal and LH-stimulated testosterone synthesis in the Leydig cells (Kasson and Hsueh, 1987), altering the responsiveness to LH (Chatelain et al., 1991). Experiments with cultures of Leydig cells and testicular cells in seminiferous tubules have shown that IGF-I may influence the process of spermatogenesis (Spiterigrech and Nieschlag, 1992).
Due to its roles in the reproductive system, IGF-I may be a candidate for selection to improve the reproductive performance in both females and males. Yilmaz et al. (1997) reported the scrotal circumference, sperm motility, and the percentage normal sperm cells to be related to blood serum IGF-I concentrations in Angus bulls. More recently, Yilmaz et al. (2004) determined the covariance components for reproductive traits and IGF-1 concentration in Angus beef cattle—suggesting that the selection for increased serum IGF-I concentration could result in increased scrotal circumference and sperm motility and, hence, a higher calving rate.
Kroonsberg et al. (1989) on the other hand, recorded no difference in conception rate between mice with high and low-IGF-I concentrations, although the high line mice produced bigger litters. Likewise, a more recent study on pregnancy rate and age of heifers at puberty and age at first calving in Angus beef cattle selected for blood serum IGF-I concentrations, showed neither pregnancy rate nor age at puberty to differ between cows with low and high-IGF-I concentrations (Yilmaz et al., 2006). Similarly, unpublished data on sheep selected for high- or low-IGF-1 concentrations, have shown a marked reduction in the reproductive performance in the low-IGF animals—without any significant increase above the controls in the high-IGF animals (H.T. Blair, P.R. Kenyon, 2010, personal communication).
No research on the relationships between IGF-1 concentration and male reproductive traits in sheep, nor in the relationship between IGF-1 and reproductive seasonality in ovine has been found in the literature. The objectives of this study were therefore to define annual changes in the relationships between serum testosterone, IGF-I and insulin and to evaluate the relationship between the circulating IGF-I concentration and the activity of the male reproductive endocrine axis. The aim was also to compare the expression of genes for IGF-I, IGF type I receptor and the “IGFBP's” (-1, -2, -3, -4, -5 and -6) in two lines of New Zealand Romney rams selected for high or low circulating IGF-I concentrations.
Section snippets
Animals
The IGF-1 sheep lines were established in 1986 from a commercial population of Romney sheep. Three IGF-1 sheep lines were generated at Massey University on the basis of an annual selection of circulating IGF-1 concentrations at 4–5 months of age—approximately 4 weeks after weaning. These lines were high (selection of ram replacements based on IGF-I concentrations ≥150 ng/mL), low (selection of ram replacements based on IGF-I concentrations ≤80 ng/mL) and an unselected line or control group (Blair
Results
Serum IGF-1 concentrations varied significantly (P < 0.001) regarding line and month of the year (Fig. 1). Throughout the entire experiment, concentrations were higher in the high line, than in the low line of IGF-1 (July, September and November, P < 0.001; March, P < 0.05; winter to autumn). In the high line, IGF-1 concentrations decreased significantly throughout the entire period between July and March. However, IGF-1 concentrations in the low line only rose above basal values in November (onset
Discussion
This study evaluated the effect of genetic selection of rams for high or low circulating concentrations IGF-1 at weaning, and the subsequent relationships between the IGF/insulin system and the hypothalamo pituitary–testis axis, of sexually mature males. Sheep are seasonal breeders, in which short days stimulate, and long days inhibit, sexual activity. The effects of photoperiod on reproductive status are mainly regulated by modifications in the activity of the gonadotrophic axis—in terms of
Conclusion
The present study indicates that rams selected for high circulating IGF-1 concentrations secreted more testosterone in response to hCG, resulting in higher levels of liver IGF-1 expression than in the low-IGF-1 line. In the testis, a significantly higher expression of IGFBP-3 (and a trend towards higher levels of expression of IGFBP-4 and -5) in the high ram line was observed, compared to rams selected for low-IGF concentrations.
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