A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies.

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation.

Effects of acute ovariectomy on the lordosis response of female rats.

The sexual receptivity of intact females with 4- or 5-day estrous cycles was compared to that of other females which had been ovariectomized at particular times during their cycles. The quality and frequency of lordosis responding were more degraded the earlier during the cycle ovariectomy was performed. This effect was more pronounced in 4-day than in 5-day cyclic females. Because exogenous progesterone was administered to all ovariectomized females, these behavioral deficits were attributed to removal of ovarian estradiol. Ovariectomy 6 hr before the critical period for luteinizing hormone release significantly shortened the duration of behavioral estrus, even though it had no effect when lordosis was tested at the time intact estrous females are maximally receptive. These findings are consistent with the hypothesis that the continual availability of estradiol throughout the 18--24 hr interval perior to the onset of behavioral estrus is essential for optimal conditioning of sexual receptivity to occur under physiological conditions. The relevance of triggering and maintenance functions of estradiol to these results is discussed.

Sex differences in response to discrete estradiol injections.

Developmental effects of perinatal androgens render adult male rats refractory to the activation of feminine sexual behavior by estradiol (E2) and progesterone (P). Recent evidence suggested that fluctuating levels of systemic E2, which are thought to approximate the ovarian secretion under physiological conditions, may reverse this insensitivity to E2 and, particularly, to the synergistic effects of P in male rats of the Wistar strain. We examined whether this hormonal regimen would reverse this insensitivity in Sprague-Dawley rats. Gonadectomized animals received two injections of E2 (1 microgram per injection) 12 hr apart at 0900 and 2100 hr followed by P (0.5 mg) or oil, at 35 hr, and a mating behavior test, at 38 hr, subsequent to the initial E2 administration. This treatment was repeated four times at 4-day intervals. The inability of Sprague-Dawley male rats to respond to E2 and P was unaffected by this pattern of exposure to exogenous E2. Receptivity scores, lordosis quotients, and proceptivity were negligible in males, and significantly less than that displayed by females. In addition, the levels of sexual receptivity and proceptivity were facilitated by the availability of P following E2 in females, but not in males. The present findings fail to support a general hypothesis that "discontinuous" E2 stimulation, achieved by two spaced injections of this hormone, reverses developmental determinants of sex differences in responsiveness to hormones mediating female sexual behaviors.

Long-term (39--51 hr) exposure to estradiol in silastic capsules and lordosis behavior of guinea pigs.

Three dosage levels of estradiol (E2) in Silastic capsules were administered to ovariectomized guinea pigs for periods of 39 or 51 hr. At 39 hr., a systemic injection of progesterone was given, and hourly testing began. Dose-dependency of various aspects of lordosis behavior was established at both time intervals, and the serum E2 levels produced by the medium and high dosage levels bracketed those found at the proestrus peak in intact guinea pigs. Although there were no significant behavioral differences between the 39- and 51-hr groups at the individual dosage levels, when the data from all three dosage groups were collapsed, exposure for 51 rather than 39 hr was seen to produce increases in maximum lordosis and heat-duration measures. The results suggest that subtle facilitative effects of estrogen occur very late in the estrogen-conditioning process (even after progesterone is administered).

Hypothalamic serotonin lesions unmask hormone responsiveness of lordosis behavior in adult male rats.

Hypothalamic lesions of serotoninergic afferents following bilateral stereotoxic injections of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the region of the ventromedial hypothalamus enhanced the effects of hormonally induced lordosis responding in both male and female rats. However, similarities and differences in the enhanced responsiveness to ovarian hormones were observed between the sexes. Compared with sham-lesioned controls, lesioned males displayed elevated lordosis responding to estradiol (E) priming alone, as well as to priming with E followed by progresterone (P). On the other hand, lesioned females displayed elevated lordosis in response to E priming alone, but were not different from controls in a synergistic facilitation of lordosis by P after E priming. With respect to receptivity, neither lesioned nor control males displayed ear-wiggling and hop-darting in response to E + P, whereas both lesioned and control females were proceptive following this treatment. Therefore, hypothalamic lesions following 5,7-DHT increase lordosis, but fail to unmask in males the responsiveness to E + P priming proceptive behaviours by females. Further, the levels of lordosis responding displayed by lesioned males are lower than those of either lesioned or control females after E + P priming, as well as those of lesioned females after E priming alone, thus indicating that other inhibitory mechanisms continue to operate in the lesioned males.