We studied the beneficial effects of dietary consumption of n-3 polyunsaturated 
fatty acids (PUFA) and two selective estrogen receptor modulator (SERM) 
derivatives (SERM-I and SERM-II) and their combined effect on serum lipids, skin 
dermis and adipose layers, bone marrow adipogenesis, and cytokine secretion in 
mice. Two different ovariectomized (OVX) models were studied: treatment began 
immediately post-OVX in one and 3 months post-OVX in the other. Our results 
showed that n-3 PUFA and both SERMs decreased triglyceride levels in the serum, 
and that SERMs also decreased serum cholesterol levels while n-3 PUFA had no 
similar effect. SERMs had no effect on IL-6, IL-1 beta, or IL-10 levels, but 
they decreased ex vivo tumor necrosis factor (TNF-alpha). N-3 PUFA decreased 
secretion of non-induced IL-6 and TNF-alpha from cultured BMC and IL-1 beta 
levels in vivo (i.e., in bone marrow plasma), but its main effect was a 
significant elevation in the secretion of IL-10, a known anti-inflammatory 
cytokine. OVX-induced B-lymphopoiesis was not affected by LY-139481 (SERM-I) 
while LY-353381 (SERM-II) exhibited an estrogen-antagonistic effect in sham and 
OVX mice and elevated the amount of B-cells in bone marrow. Fish oil consumption 
prevented the elevation in B-lymphopoiesis caused by OVX, but had no curative 
effect on established augmented B-lymphopoiesis. This activity could be mediated 
via the elevation of IL-10 which was shown to suppress B-lymphopoiesis. Both 
SERMs and n-3 PUFA inhibited the increase in adipose tissue thickness caused by 
OVX in mice. Our results showed that n-3 PUFA, could prevent some of the 
deleterious outcomes of estrogen deficiency that were not affected by SERMs. We 
observed no significant beneficial effects of the combined administration of 
SERM-I, SERM-II, and PUFA on the studied parameters.The exact mechanism by which 
polyunsaturated fatty acids exert their activities is still not clear, but 
peroxisome proliferator-activated receptors (PPARs) might be involved in 
processes which are modulated by n-3 PUFA.