there have been conflicting reports on the role of ovary ( estrogen ) and testis ( testosterone ) in growth and cholesterol metabolism . our recent study ( lee et al . , 2008 ) demonstrated that a lower growth rate in female rats was due to estrogen , which induced secretion of the stress hormone cortisol . similarly , other studies ( burgess & handa , 1992 ; lesniewska et al . , 1990 ) also showed gender differences in cortisol secretion , indicating that estrogen elevates basal levels of cortisol , corticosterone and adrenocorticotropin , and their responses to various stimuli in rats . short - term estradiol treatment to young men increased cortisol and norepinephrine concentrations in the saliva following stress over a placebo control ( kirschbaum et al . , 1996 ) . in the framingham study , the risk of cardiovascular disease was shown to be significantly increased in women who had taken estrogen ( wilson et al . , 1985 ) . ( 1996 ) reported that estrogen administration resulted in an enhanced cardiovascular response to mental stress in young menstruating women . in contrast , estrogen has long been known to exert cardioprotective effect ( barrett - connor & bush , 1991 ) , although the precise mechanism underlying its benefits is unknown ( sudhir et al . , 1997 ) . antioxidant activity of estrogen has been suggested as its role in cardioprotection ( walsh et al . , 1999 ) , but santanam et al . ( 1998 ) found no inhibitory action of estrogen on ldl oxidation at physiological concentrations . 2008 ) showed a much higher plasma cholesterol level in female than in male rats when they were fed a hypercholesterolemic diet ( cd ) . naito et al . ( 1995 ) proposed that the effect of sex hormones on lipid metabolism is not likely to account for the sex difference in cardiovascular disease . furthermore , in the 1995 ancel keys lecture , barrett - connor ( 1997 ) indicated that plasma estrogen levels do not explain coronary heart disease ( chd ) risk in either sex . in the present study , we conducted two experiments to determine the effect of gender and gonadectomy on growth , feed efficiency and plasma cholesterol levels , using pigs as a model animal to confirm the findings of our previous study done with rats ( lee et al . , 2008 ) . in experiment 1 conducted to assess the effect of gonadectomy ( gdx ) on growth and feed efficiency in female pigs , five sham - operated intact and five gdx landrace female pigs ( 26 kg ) were allowed to have free access to water and feed until they reached market weight ( approximately 100 kg ) . body weight and feed consumption were recorded biweekly , and daily body weight gain , daily feed intake and feed efficiency ( gain / feed ) were calculated during the feeding period . in experiment 2 conducted to determine the effect of gender and gdx on plasma cholesterol levels in pigs , 10 male ( 26 kg ) and 10 female ( 26 kg ) landrace pigs were used ; five male and five female pigs were assigned to sham - operated intact or gdx . pigs were allowed to have free access to water and diet without added cholesterol until they were 6 months old ( male 104 and female 98 kg ) and thereafter a hypercholesterolemic diet ( table 1 ) containing 0.5% cholesterol and 0.1% cholate for 10 days . all animal management and sampling procedures were in accordance with the guide for the care and use of agricultural animals in agricultural research and teaching ( consortium , 1988 ) . testicles were removed through a small incision in the tip of the scrotum after ligation of the spermatic cords . ovariectomy was done through a dorsal paramedial incision at the level of the lower pole of the kidneys . the surgery on pigs used in both experiments was done when they were 10 days old . at the end of feeding period , 1 ) , and from the pigs used in experiment 2 , blood samples were collected into vacutainer tubes containing edta before and after a 10-day feeding period of the hypercholesterolemic diet . plasma was prepared from the blood samples by centrifugation , and stored at -20 for later analysis . for pigs used in experiment 1 , the average value of measurements at 11 thoracic and 1 lumbar vertebra was used as the back fat thickness . total and high - density lipoprotein ( hdl ) cholesterol concentrations in plasma were determined using commercial assay kits ( international reagent corp . , low - density lipoprotein ( ldl ) plus very - low - density lipoprotein ( vldl ) cholesterol concentration was calculated by subtracting hdl cholesterol from the total . the student t - test was used to assess the effect of ovariectomy on pig performance in experiment 1 . data from experiment 2 were analyzed by the two - way analysis of variance ( sas , 1988 ) . in the analysis of variance , when the f - value in the analysis of variance was significant , the duncan 's multiple range test was used to compare individual means . in experiment 1 conducted to assess the effect of gonadectomy ( gdx ) on growth and feed efficiency in female pigs , five sham - operated intact and five gdx landrace female pigs ( 26 kg ) were allowed to have free access to water and feed until they reached market weight ( approximately 100 kg ) . body weight and feed consumption were recorded biweekly , and daily body weight gain , daily feed intake and feed efficiency ( gain / feed ) were calculated during the feeding period . in experiment 2 conducted to determine the effect of gender and gdx on plasma cholesterol levels in pigs , 10 male ( 26 kg ) and 10 female ( 26 kg ) landrace pigs were used ; five male and five female pigs were assigned to sham - operated intact or gdx . pigs were allowed to have free access to water and diet without added cholesterol until they were 6 months old ( male 104 and female 98 kg ) and thereafter a hypercholesterolemic diet ( table 1 ) containing 0.5% cholesterol and 0.1% cholate for 10 days . all animal management and sampling procedures were in accordance with the guide for the care and use of agricultural animals in agricultural research and teaching ( consortium , 1988 ) . testicles were removed through a small incision in the tip of the scrotum after ligation of the spermatic cords . ovariectomy was done through a dorsal paramedial incision at the level of the lower pole of the kidneys . the surgery on pigs used in both experiments was done when they were 10 days old . at the end of feeding period 1 ) , and from the pigs used in experiment 2 , blood samples were collected into vacutainer tubes containing edta before and after a 10-day feeding period of the hypercholesterolemic diet . plasma was prepared from the blood samples by centrifugation , and stored at -20 for later analysis . for pigs used in experiment 1 , the average value of measurements at 11 thoracic and 1 lumbar vertebra was used as the back fat thickness . total and high - density lipoprotein ( hdl ) cholesterol concentrations in plasma were determined using commercial assay kits ( international reagent corp . , low - density lipoprotein ( ldl ) plus very - low - density lipoprotein ( vldl ) cholesterol concentration was calculated by subtracting hdl cholesterol from the total . the student t - test was used to assess the effect of ovariectomy on pig performance in experiment 1 . data from experiment 2 were analyzed by the two - way analysis of variance ( sas , 1988 ) . in the analysis of variance , when the f - value in the analysis of variance was significant , the duncan 's multiple range test was used to compare individual means . overiectomy increased average daily gain ( p<0.05 ) , but had no effect ( p>0.5 ) on feed efficiency during the growing - finishing period ( table 2 ) . back fat thickness and dressing percentage in ovariectomized pigs tended to be higher ( p>0.05 ) than those found in sham - operated intact female pigs ( table 2 ) . no differences in the plasma total or hdl cholesterol levels and hdl / ldl+vldl ratio were found before feeding the hypercholesterolemic diet between sexs or between intact and gdx ( table 3 ) . however , plasma cholesterol levels in pigs fed the hypercholesterolemic diet for 10 days were much higher in females than in males ( 161 vs 104 mg/100 ml plasma ) . hdl / ldl+vldl ratio appeared to be higher ( p<0.01 ) in male than in female pigs , and was not influenced by gdx in either sex . the present pig study data ( table 2 ) support our previous findings of the rat study ( lee et al . , 2008 ) , in which depressed growth in female rats compared with male rats was mostly due to their ovarian activity . estrogen secreted in the ovary was responsible for the growth depression because the injection of estradiol markedly depressed growth in gdx rats of either sex , while enhancing plasma cortisol levels . this gender difference was abolished by ovariectomy and was reinstated by estradiol administration ( le mevel et al . , 1979 ) . the pattern of cortisol secretion was also different between sexes in the nonhuman primate macaques , and estradiol implant in castrated male macaques elicited a female pattern of plasma cortisol levels ( norman et al . , 1992 ; smith & norman , 1987 ) . in healthy men , short - term treatment with estradiol led to enhanced hypothalamic - pituitary - adrenal ( hpa ) and sympathetic responsiveness to psychological stress , resulting in increased adrenocorticotropic hormone ( acth ) , cortisol and norepinephrine concentrations in the saliva compared to the placebo ( kirschbaum et al . , 1996 ) . similarly , burgess and handa ( 1992 ) showed that corticosterone and acth levels after a 5-second footshock stress with one mamp were much higher and maintained for a prolonged time in ovx rats when administered with estradiol . in addition , they found that estrogen treatment resulted in a loss of the glucocorticoid receptor 's ability of autoregulation . interestingly , estrogen has been reported to have both stimulatory and inhibitory effects on hpa functions , depending on the time after ovariectomy and different doses of estradiol ( luber et al . , 1991 ; redei et al . , cortisol , as well as catecholaminergic responses to stress , has also been known to vary with estrous cycle in women ( collins et al . , 1985 ) and in rats ( carey et al . , 1995 ) . 2008 ) and the present pig studies , and others ' ( le mevel et al . , 1979 ; phillips & poolsaguan , 1978 ) clearly indicate that estrogen induces the secretion of hormones that increase with stress , in turn resulting in growth depression . therefore , ovariectomy may be an economically viable practice to improve growth of female pigs . studies have shown marked gender difference in plasma cholesterol levels in sprague dawley rats ( lee et al . , 1999 ; lee et al . , 2008 ) and in guinea pigs ( fernandez et al . , the present study also showed a gender difference in plasma cholesterol levels in pigs , and gonadectomy of male but not female increased plasma total cholesterol and ldl - c concentrations without decreasing hdl - c when pigs were fed the hypercholesterolemic diet ( table 3 ) . testosterone replacement therapy in hypogonadal and elderly men showed a beneficial effect on cardiovascular system , decreasing total cholesterol and atherogenic fraction of ldl - c without significant alterations in hdl - c levels or its subfractions hdl2-c and hdl3-c ( zgliczynski et al . , 1996 ) . ( 1997 ) also showed that increased testosterone levels were associated with reduced triacylglycerol and apo b ; total and ldl cholesterol concentrations ; and increased hdl / total cholesterol and hdl2-c / hdl3-c ratios . hypotestosteronemia was observed in chinese male patients with coronary heart disease ( chd ) , and positive correlation of plasma testosterone level with plasma hdl - c was found but negative correlation with plasma lp(a ) level , suggesting that testosterone had a protective effect against atherosclerosis ( zhao & li , 1998 ) . on the contrary , several studies have shown that testosterone has an adverse effect on cholesterol metabolism by altering lipoprotein profiles . total testosterone concentrations and sex hormone - binding globulin ( shbg ) were significantly associated with ldl size in men ( haffner et al . , 1996 ) . testosterone , per se , when administered at sufficiently high doses and for long durations , can significantly raise serum levels of total cholesterol , triacylglycerol , ldl - c and apo - b , meanwhile lower hdl - c levels in androgenized women , indicating that male predilection for cardiovascular disease may be due to adverse effects of high androgen levels on lipid and lipoprotein profiles ( goh et al . , 1995 ) . ( 1995 ) also showed that serum hdl - c levels were significantly depressed by intramuscular injection of testosterone enanthate ( 200 mg per week for 12 months ) , while plasma total and ldl cholesterol or triacylglycerol levels were not affected . 1997 ) reported that the plasma free testosterone level was associated with lower levels of hdl - c , but total estradiol was related to elevated levels of hdl - c in japanese men in their early fifties , supporting that testosterone may be causally associated with atherosclerosis in men through altered lipoprotein metabolism . male hamsters fed a hypercholesterolemic diet containing 0.05% cholesterol developed greater elevations in plasma total cholesterol and hdl - c levels , and a higher rate of early aortic atherosclerosis , compared with female hamsters ( wilson et al . , 1999 ) . further studies appear to be inevitable to clarify the involvement of testosterone in cholesterol metabolism , such as cholesterol synthesis ( e.g. , hmg - coa reductase gene expression ) and absorption , or cholesterol oxidation and excretion ( e.g. , cholesterol 7-hydroxylase gene expression ) . estrogen 's involvement in lipoprotein metabolism ( e.g. , an increased ratio of hdl to ldl cholesterol ) has been implicated in its role in cardioprotection ( campos et al . if estrogen plays any role at all in reducing cardiovascular disease in females , it may be through actions on other than controlling blood cholesterol levels . naito et al . ( 1995 ) indicated that the effect of sex hormones on lipid metabolism is not likely to account for the sex difference in cardiovascular disease because : 1 ) men with premature myocardial infarction was shown to have increased estrogen levels ( phillips , 1976 ) , and 2 ) men who had received high doses of estrogen showed an increased frequency of cardiovascular events ( coronary drug project research group , 1976 ; veterans administration cooperative urological research group , 1967 ) . in conclusion , ovarian activity depresses growth in female pigs and thus ovariectomy ( or inhibition of estrogen secretion or its activity ) can be an economically viable method to improve growth of female pigs . testis ( testosterone ) is responsible for the lower plasma cholesterol level in male pigs than in female pigs when they were fed hypercholesterolemic diets .