Intramammary Infusion of Leptin Decreases Proliferation of Mammary Epithelial Cells in Prepubertal Heifers

Abstract

High energy intake and excessive body fatness impair mammogenesis in prepubertal ruminants. High energy intake and excessive fatness also increase serum leptin. Our objective was to determine if an infusion of leptin decreases proliferation of mammary epithelial cells of prepubertal heifers in vivo. Ovine leptin at 100 microg/ quarter per d with or without 10 microg of insulin-like growth factor (IGF)-I was infused via the teat canal into mammary glands of prepubertal dairy heifers; contralateral quarters were used as controls. After 7 d of treatment, bromodeoxyuridine was infused intravenously and heifers were slaughtered approximately 2 h later. Tissue from 3 regions of the mammary parenchyma was collected and immunostained for bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (Ki-67), and caspase-3. Leptin decreased the number of mammary epithelial cells in the S-phase of the cell cycle by 48% in IGF-I-treated quarters and by 19% in saline-treated quarters. Leptin did not alter the number of mammary epithelial cells within the cell cycle, as indicated by Ki-67 labeling. Caspase-3 immunostaining within the mammary parenchyma was very low in these heifers, but leptin significantly increased labeling in saline-treated quarters. Leptin enhanced SOCS-3 expression in IGF-I-treated quarters but did not alter SOCS-1 or SOCS-5 expression. We conclude that a high concentration of leptin in the bovine mammary gland reduces proliferation of mammary epithelial cells. The reduced proliferation is accompanied by an increase in SOCS-3 expression, suggesting a possible mechanism for leptin inhibition of IGF-I action. Whether leptin might be a physiological regulator of mammogenesis remains to be determined.

Staphylococcus aureus intramammary infection affects milk yield and SCC of dairy cows

“…The percent decrease of lactose, however, is relatively small (Pyörälä 2003), and that was not affected by S. aureus subclinical infection during the present study. Given the expected differences of milk production (Natzke et al 1965) between front and rear quarters and the significant differences already reported on milk constituents between healthy and unhealthy ones (Nielsen et al 2005), it was essential that the statistical model adopted (Silva et al 2008) consider such fixed factors of variations. S. aureus IMI had markedly affected the SCC of both front and rear infected quarters, but tissue damage seemed to be more evident in front quarters than in rear ones, and that could be partially explained by a dilution effect due to the normal 40:60 milk production ratio between them (Natzke et al 1965), which may have accounted for the S*H interaction observed in the present study.…”

Leptin in farm animals: where are we and where can we go?

“…In an in vitro study, they found that larger leptin doses were needed when the media was supplemented with IGF-1. Silva et al (2008) infused recombinant ovine leptin and IGF-1 for 7 days into separate quarters of prepubertal heifers fed to gain at 700 g/day, but retaining normal mammary development. The IGF-1 dose (10 mg/quarter per day) had previously raised epithelial cell proliferation by , 50% (Silva et al, 2005) while the leptin dose (100 mg/qtr per day) ensured supraphysiological leptin levels in the parenchyma (higher by , 25 3 than with placebo).…”

Cow management modulates gene expression in the mammary gland, a possible epigenetics role

“…That number can be changed by different factors (such as nutrition (Silva et al, 2008), health (Wagner et al, 2009), and heat stress (Collier et al, 2006). Changes in management that occur during lactation and even before the onset of lactation (dry period) can modify milk production.…”