J. J. Bass

Management, nutrition, production, and genetics are the main reasons for the decline in fertility in the modern dairy cow. Selection for the single trait of milk production with little consideration for traits associated with reproduction in the modern dairy cow has produced an antagonistic relationship between milk yield and reproductive performance. The outcome is a multi-factorial syndrome of subfertility during lactation; thus, to achieve a better understanding and derive a solution, it is necessary to integrate a range of disciplines, including genetics, nutrition, immunology, molecular biology, endocrinology, metabolic and reproductive physiology, and animal welfare. The common theme underlying the process is a link between nutritional and metabolic inputs that support complex interactions between the gonadotropic and somatotropic axes. Multiple hormonal and metabolic signals from the liver, pancreas, muscle, and adipose tissues act on brain centers regulating feed intake, energy balance, and metabolism. Among these signals, glucose, fatty acids, insulin-like growth factor-I, insulin, growth hormone, ghrelin, leptin, and perhaps myostatin appear to play key roles. Many of these factors are affected by changes in the somatotropic axis that are a consequence of, or are needed to support, high milk production. Ovarian tissues also respond directly to metabolic inputs, with consequences for folliculogenesis, steroidogenesis, and the development of the oocyte and embryo. Little doubt exists that appropriate nutritional management before and after calving is essential for successful reproduction. Changes in body composition are related to the processes that lead to ovulation, estrus, and conception. However, better indicators of body composition and measures of critical metabolites are required to form precise nutritional management guidelines to optimize reproductive outcomes. The eventual solution to the reduction in fertility will be a new strategic direction for genetic selection that includes fertility-related traits. However, this will take time to be effective, so, in the short term, we need to gain a greater understanding of the interactions between nutrition and fertility to better manage the issue. A greater understanding of the phenomenon will also provide markers for more targeted genetic selection. This review highlights many fruitful directions for research, aimed at the development of strategies for nutritional management of reproduction in the high-producing subfertile dairy cow.

ABSTRACT The relationship between plasma GH profiles and circulating concentrations of insulin-like growth factor 1 (IGF-1) at three different planes of nutrition, chosen to represent a high, medium and low level of nutrition (3%, 1·8% and 1% dry matter of liveweight per day) was studied in 15 young Angus steers. All steers were maintained on 3% dry matter for 5 weeks, then on one of the three nutritional planes for 4 weeks and then all were returned to 3% dry matter for 3 weeks. Blood was sampled through jugular catheters at 15-min intervals for 25 h at the end of each phase of the study and additional samples were taken on 2 days each week. Pulsatile release of GH occurred episodically with a diurnal increase during night and morning hours only in steers on high nutritional intakes. Reduced feeding at both the medium and the low plane abolished the diurnal rhythm and significantly increased mean plasma GH concentrations, the amplitude of GH pulses and the area under the GH profiles. Baseline concentrations of GH and pulse frequency did not change through nutritional manipulation. Upon realimentation, plasma GH concentrations decreased in both previously undernourished groups, with those fed 1% dry matter still having increased levels 10 days after refeeding. Plasma IGF-1 concentrations showed no periodicity. With nutritional deprivation, a decrease in IGF-1 concentration was observed only at negative energy balance (1% group). In this group plasma IGF-1 concentrations were progressively restored within 1 week of realimentation. The different relationship between GH and IGF-1 release at each plane of nutrition suggests that at both medium and low levels of feed intake, tissue insensitivity to GH may exist peripherally and perhaps centrally. It is suggested that nutritional status may, through modulation of tissue sensitivity to GH, be a primary factor in determining growth and the regulation of the somatotrophic axis in the postnatal ruminant. J. Endocr. (1986) 111, 209–215

ABSTRACT Plasma GH profiles and circulating concentrations of plasma insulin-like growth factors-I and -II (IGF-I and -II) were examined in 20 steers on either high (3% dry matter of body weight per day) or low (1% dry matter of body weight per day) planes of nutrition with or without an implant of oestradiol-17β. The response of plasma IGF-I and -II to a bolus injection of bovine GH (bGH) was also investigated. Reduced feeding significantly ( P <0·01) increased the mean concentration, peak height and integrated area of plasma GH. Treatment of steers with oestradiol at low nutrition significantly increased baseline GH concentrations. Treatment of steers with oestradiol at high nutrition significantly ( P <0·05) increased mean, baseline, peak height, and integrated area of plasma GH. GH pulse frequency was not changed by either nutritional plane or oestradiol treatment. Basal concentrations of plasma IGF-I were significantly ( P <0·01) decreased by reduced feeding in both the oestradiol-treated and the control group. Treatment with oestradiol increased ( P <0·01) basal plasma concentrations of IGF-I at both high and low levels of nutrition. After i.v. injection of bGH (0·1 mg/kg body weight), an increase in plasma IGF-I was observed only in steers at high nutrition. Basal concentrations of plasma IGF-II were not altered by nutritional manipulations but were significantly ( P <0·001) increased by oestradiol treatment. After bGH infusion only steers at high nutrition showed an increase in plasma IGF-II. Significant correlations were observed between daily body weight gain and plasma concentrations of IGF-I ( r = 0·91, P <0·001, n = 20) and also between the capacity of the high-affinity hepatic somatotrophic receptor and plasma IGF-I ( r = 0·89, P <0·001, n= 10). Decreased plasma concentrations of IGF-I at a low level of nutrition may abolish the growth-promoting activity of circulating GH. The increase in both GH secretion and the number of somatotrophic receptors with oestradiol treatment may represent a coordinated response of the somatotrophic axis leading to enhanced IGF-I and -II production and improved growth rate. The inferential relationships between the capacity of the high-affinity somatotrophic receptor, plasma concentrations of IGF-I and growth rates suggest that active modulation of somatotrophic receptors is an important regulatory constituent of the somatotrophic axis. J. Endocr . (1988) 118, 243–250

ABSTRACT The binding of bovine GH (bGH) to hepatic membranes obtained from steers on either high (3% dry matter of body weight per day) or low (1% dry matter of body weight per day) planes of nutrition with or without an oestradiol-17β implant was studied ( n = 5 per group). Binding studies were performed on both crude membrane homogenates and on 100 000 g microsomal membrane fractions; identical results were obtained using both preparations. In all four groups of animals, linear Scatchard plots were obtained, but following pretreatment of the membranes with MgCl 2 to remove endogenously bound hormone, curvilinear plots were obtained in the groups on the high plane of nutrition. Analysis of these curves suggested the presence of a high- and low-affinity binding site, the high-affinity site being fully occupied in the absence of MgCl 2 pretreatment. The specific binding of bGH in MgCl 2 -pretreated crude membranes was greater ( P < 0·01) in well-fed steers (14·8 ± 1·6%) than in poorly fed steers (9·8 ± 0·9%). Scatchard analysis showed this to be due to the presence of a high-affinity site (dissociation constant ( K d ) = 11·6 ± 3·3 pmol/l) in the well-fed animals only. In addition, there was an increase ( P < 0·01) in the affinity, but not in the capacity, of the low-affinity site ( K d = 106·4 ± 22·8 pmol/l in well-fed steers and 197·0 ± 23·8 pmol/l in poorly fed steers). Oestradiol treatment was associated with an increase ( P < 0·01) in specific binding at both planes of nutrition, but binding was higher ( P < 0·01) in well-fed (24·8 ± 2·9%) than in poorly fed (15·6 ± 3·7%) steers. Scatchard analysis after MgCl 2 pretreatment again showed a curvilinear plot at the high and a linear plot at the low nutritional plane. The effect of oestradiol was to increase ( P < 0·001) the capacity of the high-affinity site from 1·87 ± 0·61 pmol/100 mg in the control well-fed group to 6·56 ± 1 ·2 pmol/100 mg. The capacity of the low-affinity site was increased ( P < 0·01) from 20·1 ± 2·6 to 30·1 ± 3·2 pmol/100 mg in the well-fed group, with a similar change in the poorly fed group. Oestradiol had no effect on the apparent affinity of either binding site. These studies demonstrate a heterogeneity of somatotrophic binding sites of hepatic membranes in steers. The presence of a high-affinity site is determined by nutritional status, whereas oestradiol primarily affects receptor capacity. Thus nutrition and oestradiol have independent and qualitatively different effects on somatotrophic binding. As the rate of weight gain correlated ( P < 0·01) with the capacity of the high-affinity site, it is suggested that somatotrophic receptor modulation is a primary factor in the regulation of somatic growth in the ruminant. J. Endocr. (1988) 116, 169–177