Biomedical subjects

David R Mann

Publications and source records attributed to David R Mann.

3 recordsLinked to original sources

PubMed2003

Does leptin mediate the effect of photoperiod on immune function in mice?

Seasonal fluctuations in immune status have been documented for avian and mammalian populations. During the late summer and early fall, immune function is bolstered to help animals cope with the more physiologically demanding winter. The environmental cue for these seasonal changes is apparently decreasing photoperiod. In the present study, we determined the potential role of leptin in mediating the effect of photoperiod on cell-mediated immune responses in male mice. Leptin-deficient (ob/ob) and littermate control mice were housed for 10 wk in either a short (8L:16D) or a long (16L:8D) photoperiod beginning at 6 wk of age. After the mice were killed, immune and reproductive organs were weighed and splenocytes isolated. The proliferative and cytokine responses (interleukin [IL]-2 and IL-4) of splenocytes to the T-cell mitogen, concanavalin A (Con A; 0-40 microg/ml), were determined. Body weights were elevated and both testes and seminal vesicle weights subnormal in ob/ob mice (by ANOVA, main effect of leptin deficiency), but thymuses and spleens were of normal size. Serum leptin levels were at minimum detection limits in ob/ob mice, but leptin levels in control mice housed at 8L:16D were higher than in control mice housed at 16L:8D. The proliferative response of splenocytes from ob/ob mice to Con A was subnormal (by ANOVA, main effect of leptin deficiency), but photoperiod had no effect on this response. Production of IL-2 in splenocytes of ob/ob mice was subnormal (by ANOVA, main effect of leptin deficiency) irrespective of photoperiod, but cells from mice housed at 8L:16D (by ANOVA, main effect of photoperiod) produced more IL-2 than cells from animals housed at 16L:8D. In contrast, a leptin deficiency did not alter IL-4 production, but cells from animals (ob/ob and controls) housed at 16L:8D produced less IL-4 than cells from animals housed at 8L:16D (by ANOVA, main effect of photoperiod). The present study suggests that both photoperiod and leptin have mutually independent effects on the proliferation of lymphocytes and cytokine production profiles. The data do not provide definitive support for the hypothesis that photoperiod-induced changes in leptin secretion mediate the effects of season on immune status.

Animals↗

PubMed2003

Changes in circulating leptin, leptin receptor, and gonadal hormones from infancy until advanced age in humans.

We determined developmental changes in circulating levels of the soluble leptin receptor (sOB-R), leptin, and gonadal hormones in human subjects. In both sexes the rise in leptin with age was associated with a decline in sOB-R, and age-related changes in both parameters preceded the pubertal rise in gonadal hormones. Leptin levels above 10 ng/ml were a strong predictor of sOB-R concentrations, but this predictive value decreased as leptin declined. In young subjects there were no gender differences in serum leptin, but boys had higher sOB-R levels. In adults neither leptin nor sOB-R changed with age, but serum leptin was higher and sOB-R was lower in women than men. There was a significant negative correlation between sOB-R and leptin in women, but not men. The data suggest that bioavailable leptin in the circulation may be increasing more rapidly during development than indicated by total leptin levels, and that these changes may serve as one of the signals to the central nervous system that metabolic conditions are adequate to support pubertal development. Furthermore, the study provides suggestive evidence that leptin regulates the secretion of its own binding protein, but it also appears that an additional gender-specific, leptin-independent, regulatory mechanism is functional before puberty.

Adolescent↗

PubMed2002

Leptin and pubertal development.

Sexual development after birth in rodents, nonhuman primates, and humans is driven by the gonadotropin-releasing hormone (GnRH) pulse generator. During the neonatal period in primates, pulsatile GnRH discharge from the medial basal hypothalamus drives an active period of pituitary gonadotropin and gonadal hormone secretion. During the transition from the neonatal to the juvenile period, however, the activity of the GnRH pulse generator is restrained or arrested and gonadotropin and gonadal hormone secretion enters a quiescent period that continues until the onset of puberty. As puberty approaches the GnRH pulse generator is reactivated, resulting in enhanced gonadotropin secretion, accelerated growth, maturation of the gonads, and the achievement of sexual competence. Rodents do not appear to exhibit a developmental phase analogous to the quiescent juvenile period in primates when the GnRH pulse generator is held in check. Instead, progressive maturational changes in the pattern of GnRH pulsatility appear to drive sexual development in rodents. The role that leptin plays in sexual development has not been fully defined, but the balance of current evidence appears to support the idea that, in both rodents and primates, leptin plays a permissive rather than a causal role in timing this process. When body energy reserves rise above a critical level, blood leptin increases to a threshold concentration signaling to the central nervous system that the body can support sexual function. Puberty can apparently occur over a wide range of concentrations above this critical leptin threshold. Leptin does not appear to act as a trigger to time the initiation of puberty but, instead, once leptin reaches this threshold pubertal development may proceed if, and only if, other critical control mechanisms are operational.

Animals↗