Lack of effect of epidermal growth factor treatment in late-pregnant ewes on subsequent lactation

1991 ◽  
Vol 58 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Christine B. Gow ◽  
Debbi J. Singleton ◽  
Mervyn J. Silvapulle ◽  
G. Philip M. Moore

SummaryTwin-bearing ewes were treated with epidermal growth factor (EGF) to determine its effect on mammogenesis and resultant milk production and composition. The EGF was infused intravenously at a dose rate of O5 mg/d in 300 ml saline between days 117 and 139 of gestation; control animals received placebo infusions of saline. All animals then received continuous infusions of 300 ml/d saline on days 139–144. Following parturition 1–5 d later, ewes were milked by hand for 10 d and thereafter were machine-milked until day 16 of lactation. At this level of treatment, EGF was not detected in the circulation during infusion and feed intake was not affected. All ewes gave birth to healthy twin lambs. There were no effects of EGF on birth weights of lambs, live weights of ewes or lengths of gestation. An EGF immunoreactive material was detected in the mammary secretions of control ewes at a mean concentration of 2 μg/l on day 1 of lactation. Two ewes had detectable levels on day 2, but none was found in the milk thereafter. In the EGF-infused group, concentrations of EGF in colostrum were ñ 10 times higher than in the control ewes on day 1 of lactation and EGF was detected in mammary secretions on day 2 but not in subsequent milk samples. A range of 0·3–0·5% of the EGF infused appeared in mammary secretions over the first 2 d of lactation. No other differences were observed for colostrum composition, subsequent milk yield or composition between the two groups of ewes indicating that mammary gland development and function were unaffected. The levels of EGF observed in the mammary secretions of treated and control ewes indicate that the mammary glands accumulate and store EGF in the pre partum period.

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2301-2313 ◽  
Author(s):  
Mark D. Aupperlee ◽  
Yong Zhao ◽  
Ying Siow Tan ◽  
Jeffrey R. Leipprandt ◽  
Jessica Bennett ◽  
...  

It is well documented that macrophages and eosinophils play important roles in normal murine pubertal mammary gland development. Although it is accepted that estrogen (E) and progesterone (P) are key players in mammary gland development, the roles these hormones might play in regulating the actions of leukocytes in that process is an understudied area. We show here that P and E, respectively, induce unique, but overlapping, sets of proinflammatory and angiogenic cytokines and chemokines, in the pubertal female BALB/c mammary gland, as well as induce infiltration of macrophages and eosinophils to the mammary periepithelium. This extends earlier studies showing P induction of proinflammatory products in pubertal and adult mammary epithelial organoids and P-induced in vivo infiltration of leukocytes to the adult mammary periepithelium. Importantly, epidermal growth factor receptor-signaling, which is likely mediated by amphiregulin (Areg), a downstream mediator of E and P, is both necessary and sufficient for both E- and P-induced recruitment of macrophages and eosinophils to the pubertal mammary periepithelium. We further show that receptor activator of nuclear factor κB ligand (RANKL), although not sufficient of itself to cause macrophage and eosinophil recruitment, contributes to an optimal response to P. The potency of Areg is highlighted by the fact that it is sufficient to induce macrophage and eosinophil recruitment at levels equivalent to that induced by either E or P. Our finding of a dominant role for Areg in hormonally induced leukocyte recruitment to the pubertal mammary gland parallels its dominance in regulating ductal outgrowth and its role in P-induced proliferation in the pubertal gland.


1992 ◽  
Vol 82 (5) ◽  
pp. 573-580 ◽  
Author(s):  
M. Salleh ◽  
M. Ardawi

1. The effects of parenteral nutrition with or without glutamine supplementation and epidermal growth factor treatment (0.15 μg/g body weight) was studied in the small bowel of septic rats after 4 days. 2. Septic rats infused with glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment survived sepsis significantly better than other septic rats given parenteral nutrition. The cumulative percentage of deaths over 4 days in septic rats infused with glutamine-supplemented parenteral nutrition was 20% (without epidermal growth factor) and 15% (with epidermal growth factor) compared with 50% in septic rats treated with parenteral nutrition without glutamine and 35% in septic rats given parenteral nutrition without glutamine but with epidermal growth factor treatment. 3. Glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment resulted in improved nitrogen balance in septic rats. The cumulative nitrogen balance over the 4 day period was the least negative as compared with other groups of septic rats. 4. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited marked increases in intestinal net rates of utilization of glutamine (P < 0.001) and production of ammonia (P < 0.001) compared with septic rats given parenteral nutrition without glutamine and/or epidermal growth factor treatment. 5. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited significant increases in jejunal wet weight (by 32.4–40.6%), DNA content (by 24.2–34.7%), protein content (by 29.1–50.0%), villus height (by 16.3–26.4%) and crypt depth (by 20.3–29.6%) compared with other groups of septic rats. 6. The rate of intestinal [3H]thymidine incorporation in vivo and thymidine kinase activity in vitro were significantly increased (P < 0.001) in septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor. 7. The activity of jejunal glutamine synthetase was lower (by 66.3–90.0%) in septic rats treated with glutamine, epidermal growth factor or glutamine and epidermal growth factor, whereas glutaminase activity was increased (by 28.1–31.0%) in response to parenteral nutrition supplemented with glutamine only. 8. It is concluded that the administration of glutamine-supplemented parenteral nutrition, with or without epidermal growth factor, is beneficial to the small bowel of septic rats.


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