Polycystic ovary syndrome: evidence for reduced sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone

Plasma LH is commonly elevated in women with the polycystic ovary syndrome (PCOS), but the underlying mechanisms are uncertain. We tested the hypothesis that the elevated LH in part reflects a reduced sensitivity of the hypothalamic GnRH pulse generator to suppression by estradiol (E2) and progesterone (P). In an initial protocol, normal controls (beginning on cycle days 8-10) and women with PCOS were given E2 transdermally and P by vaginal suppository (three times daily), to achieve plasma concentrations similar to those in the midluteal phase of an ovulatory cycle, for 21 days. Blood was obtained at 10-min intervals for 12 h before and on days 5, 10, 20, and 28 (7 days after E2 and P were discontinued). LH pulse amplitude and LH pulse frequency were suppressed in both PCOS and normal controls, but LH pulse frequency fell more rapidly in controls and was lower by day 10 (P < 0.05). Based on this time course a dose-response study was performed, in which E2 in constant dosage and varying concentrations of P were administered for 7 days. Pulsatile LH release was appraised on days 1 and 7. The frequency of LH pulse secretion was reduced in controls and was lower than that in patients with PCOS on day 7 (P < 0.0001). Plasma P concentrations of 13-15 ng/mL suppressed LH pulse frequency to a similar degree in PCOS and controls. In contrast, lower concentrations (P < 10 ng/mL) were more effective in suppressing GnRH/LH pulse frequency in controls (by > 45% of basal) than in PCOS (< 40%; P < 0.01). The data indicate that E2 and P can inhibit the activity of the hypothalamic GnRH pulse generator in women with PCOS. However, higher plasma concentrations of P were required to reduce GnRH/LH pulse frequency in PCOS compared to controls, suggesting an insensitivity of the GnRH pulse generator to suppression by E2 and P. These results suggest that an abnormality in the regulation of hypothalamic GnRH secretion is present in PCOS and may be a factor in the etiology of the disorder in adolescence.     

A simple parasite model with complicated dynamics

During their first year of life sheep acquire parasites through grazing, and simultaneously build up an immunity to infection. At the beginning of each year non-immune lambs are introduced onto contaminated pasture. We represent this process by differential equations describing the within-year dynamics, and defining a difference equation that describes the between-year dynamics. An example with two system parameters is analysed in detail. It is shown that regions exist in parameter space where periodic (between-year) or aperiodic solutions occur. Parasite control schemes could change the system dynamics from a stable equilibrium to complicated long-term fluctuations.     

Immunonutrition: the role of carbohydrates

The major role for carbohydrates in the diet is for the provision of energy. Most non-energy-related effects of carbohydrates can be related to short-chain fatty acid production or other effects of bacterial fermentation in the colon. More complex or slowly absorbed carbohydrates may also reduce glycemic index and insulin production and therefore may have a less profound effect on modification of lipid metabolism. Certain carbohydrates may promote fermentation in the colon, increasing short-chain fatty acid production and may alter bacterial flora in the small bowel and colon. Increased insoluble fiber will increase fecal bulk. Further immunomodulary effects of carbohydrates have had little attention in the literature. This would be a potential opportunity for further investigation.     

Effects of psychopathology and demographic characteristics on MMPI-2 scale scores

Using multiple linear regression analyses, we examined the effects of subject status for 6 demographic variables and the presence of psychopathology on variance in MMPI-2 scale scores. The analyses were designed to measure the incremental contribution of the demographic variables to scale variance beyond that explained by presence of psychopathology. Demographic variables were found to contribute little incremental variance for the validity and clinical scales, but did explain more than 10% of the score variance for 1 clinical scale, 2 content scales, and 5 supplemental scales. For these 8 scales, gender was most often the potent demographic variable and an expected influence. The results are discussed in light of the use of gender-based norms and in terms of other potential factors that might explain MMPI-2 scale score variance.