Early lactation in dairy cattle is a period of severe negative energy balance (NEB) characterized by reduced blood glucose and insulin concentrations and elevated blood GH concentrations. The liver is refractory to GH during NEB and this uncoupling of the GH-IGF axis results in diminished plasma concentrations of IGF-I. Our objectives were to examine the effects of insulin administration during the immediate postpartum period on plasma IGF-I and GH concentrations and to examine the hepatic expression of total GH receptors (all GH receptor transcripts), GH receptor 1A (GHR 1A) and IGF-I. In addition, we examined adipose tissue for total GH receptor and IGF-I mRNA levels to establish the effects of chronic hyperinsulinemia on an insulin-responsive peripheral tissue. Holstein cows (n=14) were subjected to either a hyperinsulinemic-euglycemic clamp (insulin; INS) or saline infusion (control; CTL) for 96 h starting on day 10 postpartum. Insulin was infused i.v. (1 µg/kg body weight per h), blood samples were collected hourly, and euglycemia was maintained by infusion of glucose. Insulin concentrations during the infusions were increased 8-fold in INS compared with CTL cows (2·33 0·14 vs 0·27 0·14 ng/ml (S.E.M.); P<0·001) while blood glucose concentrations were not different between treatments (45·3 2·2 vs 42·5 2·2 mg/dl; P>0·1). Plasma IGF-I increased continuously during the insulin infusion, and reached the highest concentrations at the end of the clamp, being almost 4-fold higher in INS compared with CTL cows (117 4 vs 30 4 ng/ml; P<0·001). Hepatic expression of GHR 1A and IGF-I mRNA was low in CTL cows, but was increased 3·6-fold (P<0·05) and 6·3-fold (P<0·001) respectively in INS cows. By contrast, in adipose tissue the changes in gene expression in response to insulin were reversed with decreases in both total GHR and IGF-I mRNA. The expressions of GHR 1A and IGF-I mRNA in liver tissue were correlated in INS (r=0·86; P<0·05), but not CTL cows (r=0·43; P>0·1). Insulin appears to be a key metabolic signal in coupling the GH-IGF axis, thus orchestrating a marked elevation in circulating IGF-I concentrations.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) control growth and lactation in cattle and swine. Insulin participates in the endocrinology of growth and lactation because insulin and GH are antagonistic in their actions. Dairy cows experience a period of negative energy balance during the first 4-8 weeks post-partum. During this period, their somatotropic axis (comprised of GH, the GH receptor and IGF-I) becomes uncoupled and there is elevated GH and diminished IGF-I in the circulation. Blood insulin concentrations are low as well. Sows are different from dairy cows because their somatotropic axis remains coupled during lactation and both GH and IGF-I are elevated. Nonetheless, sows that become catabolic during lactation will have reduced IGF-I concentrations. Sows are inseminated after weaning so their metabolic state is different from post-partum beef and dairy cows that are inseminated when they are lactating. Dairy cows are fed ad libitum and naturally have low IGF-I during lactation. Sows have elevated IGF-I when they are well-fed. A threshold of IGF-I protein in follicular fluid may be met by local ovarian (paracrine/autocrine) and endocrine sources of IGF-I. Nutritionally induced changes in insulin and in liver IGF-I secretion that arise from perturbations of the somatotropic axis have a direct effect on the ovary through the endocrine actions of insulin and IGF-I. Sows and cows that are nutritionally compromised have low concentrations of insulin and IGF-I in their blood and this theoretically reduces ovarian responsiveness to gonadotropins. Although sows are inseminated after weaning, there appear to be carry-over effects of the previous lactation on the ovarian follicular populations that develop after the sow is weaned. Understanding the mechanisms through which metabolic hormones control ovarian function may lead to improved reproductive management of both pigs and cattle because lactation and post-partum reproduction are closely tied in both species.

We investigated the effect of increasing nutrient intake on the responsiveness of the GH/IGF-I system in calves fed a high-protein milk replacer. Fifty-four Holstein bull calves were fed one of three levels (low, medium, and high; n = 18 per treatment) of a 30% crude protein, 20% fat milk replacer to achieve target rates of gain of 0.50, 0.95, or 1.40 kg/d, respectively, for low, medium, and high. Six calves per treatment were slaughtered at approximately 65, 85, and 105 kg BW. Additionally, six calves were slaughtered at 1 d of age to provide baseline data. Plasma aliquots from blood samples collected weekly were analyzed for IGF-I, insulin, glucose, NEFA, and plasma urea nitrogen (PUN). Plasma IGF-I and insulin, measured weekly, increased (P < 0.001) with greater nutrient intake from wk 2 of life to slaughter. Plasma glucose and NEFA also increased (P < 0.05) with nutrient intake. In addition, each calf underwent a GH challenge beginning 4 d before the scheduled slaughter. Plasma from blood collected before the first GH injection and 14 and 24 h after the third injection was analyzed for IGF-I and PUN. Response to challenge, calculated as the absolute difference between the prechallenge and 14-h postchallenge plasma IGF-I concentrations, was significant in calves on all three treatments. Plasma urea nitrogen was not different among treatments as measured weekly but decreased (P < 0.001) following GH challenge in all calves. Results of ribonuclease protection assays showed increased expression of hepatic mRNA for GH receptor 1A and IGF-I with increased intake. The amounts of GH receptor and IGF-I mRNA in muscle and adipose, however, were not affected by intake. In summary, plasma IGF-I was elevated in calves with increased nutrient intake, and the elevations in plasma IGF-I following short-term administration of GH were significant in all calves by 65 kg BW. Data demonstrate that in well-managed milk-fed calves the somatotropic (GH/IGF-I) axis is functionally coordinated and sensitive to nutrient intake and GH.

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Summary ― The effect of dietary energy balance (EB) on growth of ovarian follicles was tested. Cows (n = 9) were fed a high energy diet (HE diet; positive EB; n = 4) or switched to a low energy diet (LE diet; negative EB; n = 5) during the preovulatory period. Non-esterified fatty acids (NEFA) were greater in cows fed the LE diet. Concentrations of luteinizing hormone (LH) were similar in HE and LE cows. However, the growth of preovulatory follicles in cows fed the LE diet was 50% that of cows fed the HE diet. Insulin-like growth factor-I (IGF-I) in plasma was less in LE-fed cows compared with HE-fed cows, and plasma IGF-I was positively correlated to estrogen: progesterone ratio in follicular fluid of dominant follicles. In summary, slower follicular growth in cows fed an LE diet occurred despite normal plasma LH and coincided with reduced IGF-I and elevated NEFA in plasma.