Recent studies have indicated that follicle-stimulating hormone (FSH) promotes bone loss. The present study tested the hypothesis that FSH enhances the activity of bone-resorbing cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6], either by inducing their secretion or by altering their receptor expression. Thirty-six women between the ages of 20 and 50 were assessed for bone mineral density (BMD), reproductive hormone, cytokine ligand and soluble receptor concentrations, and surface expression of cytokine receptors on monocytes. In addition, isolated mononuclear cells were incubated in vitro with exogenous FSH. Univariate regression analyses indicated that BMD was inversely related to serum FSH (r = -0.29 to -0.51, P = 0.03-0.001, depending upon the skeletal site). Physical activity and body composition were also identified as significant factors by multiple regressions. Exogenous FSH induced isolated cells to secrete IL-1beta, TNF-alpha, and IL-6 in proportion to the surface expression of FSH receptors on the monocytes. Endogenous (serum) FSH concentrations correlated with the circulating concentrations of these cytokines. None of these individual cytokines was related to BMD, but the IL-1beta to IL-1 receptor antagonist (IL-1Ra) ratio was inversely related to BMD (r = -0.53, P = 0.002) in all but the most physically active women, who had significantly lower expression of IL-1 type I receptors relative to type II (decoy receptors, P = 0.01). Physical activity also correlated positively with secretion of inhibitory soluble IL-1 receptors (r = 0.53, P = 0.003). Moreover, IL-1Ra correlated strongly with percent body fat (r = 0.66, P < 0.0001). These results indicate that BMD is related to FSH concentration, physical activity, and body composition. Although each of these factors likely has direct effects on bone, the present study suggests that each may also influence BMD by modulating the activity of the osteoresorptive cytokine IL-1beta.

Elevated serum concentrations of follicle-stimulating hormone (FSH) are associated with diminished bone density in women, beginning years before menopause and the decline in estradiol. We hypothesized that FSH promotes development of myeloid cells toward the boneresorbing osteoclast phenotype. This was tested by isolating peripheral blood mononuclear cells from nine healthy adults, incubating them in the presence of FSH at three different concentrations spanning the physiological range, and then measuring the expression of receptor activator for NF-κB (RANK, a surface marker for osteoclasts) on CD14 + cells by flow cytometry. In the absence of FSH, 3.3 ± 0.5% of the cells expressed high levels of the receptor (RANK high ). Increasing concentrations of FSH caused a biphasic dose-response, with a maximal (1.5-fold) increase in RANK high cells achieved with 50 mIU/ml FSH (P = 0.02). Cytokines that influence development of osteoclasts were also measured in culture supernatants: Macrophage colony stimulating factor (M-CSF), osteoprotegerin (OPG) and tumor necrosis factor-α (TNFα) concentrations were not significantly influenced by FSH, whereas RANK-ligand was undetectable. This study supports the concept that the elevated circulating concentrations of FSH during perimenopause may contribute to the increased rate of bone loss by promoting the development of osteoclast precursor cells. Keywordshuman; monocytes; RANK; follicle-stimulating hormone; flow cytometry IntroductionThe development of osteoporosis in older women is often associated conceptually with the decline in circulating estradiol concentration that accompanies menopause. However, studies involving pre-and perimenopausal women have shown that elevated serum concentrations of follicle-stimulating hormone (FSH) correlate with diminished bone mineral density (BMD) beginning years before menopause and the decline in estradiol [1,2]. In addition, a meta-analysis of ten prospective studies found that the rate of spinal BMD loss during perimenopause, when estradiol concentrations were still high, was greater than the rate of loss in the years following menopause, when estradiol concentrations were much lower [3].

Cytokine receptor subunits are released from cells in a regulated manner and circulate in soluble forms at concentrations that are orders of magnitude greater than the concentrations of the cytokines themselves. The purpose of this study was to determine if the circulating concentrations of soluble receptor subunits for interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) might serve as early indicators of vascular dysfunction independent of the traditional cardiovascular disease (CVD) risk factors in women. Healthy women, aged 20-50 years (n = 36), were assessed for circulating concentrations of the cytokines IL-1β, IL-6 and TNFα and the soluble cytokine receptor subunits interleukin-1 receptor type I (sIL-1RI), sIL-1RII, sIL-6Rα, glycoprotein 130 (s-gp130), soluble TNF receptor type 1 (sTNFR1), and sTNFR2, along with traditional CVD risk factors. Cytokine receptor subunit expression on mononuclear cells and the release of these subunits in vitro were also determined. Brachial artery flow-mediated dilation (FMD), carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cfPWV) were assessed by ultrasonography and Doppler probes. Circulating sIL-6Rα correlated negatively with FMD (r = −0.56, p = 0.007) independent of age and other CVD risk factors. Circulating sTNFR1 correlated positively with cfPWV (r = 0.60, p = 0.002). TNFR1 receptor expression on monocytes correlated positively with cIMT (r = 0.51, p = 0.004). Plasma concentrations of IL-1β, IL-6 and TNFα were not significantly associated with FMD, cIMT or cfPWV. These data suggest that the receptors for IL-6 and TNFα, rather than the cytokines themselves, may be better indicators of early vascular changes that are associated with CVD.

Several studies worldwide have demonstrated significant relationships between meteorological parameters and stroke events. However, authors often reported discordant effects of both barometric pressure and air temperature on stroke occurrence. The present study investigated whether there was an association between weather parameters (barometric pressure and temperature) and ischemic stroke hospitalization. The aim of the study was to find out whether daily barometric pressure may be used as a prognostic variable to evaluate the workload change of a neurological intensive care unit. We conducted a retrospective review study in which we collected the independent (barometric pressure and temperature) and dependent variables (stroke hospitalization) every 24 h for the periods 10/1/2016-4/30/2017 at Augusta University Medical Center of Augusta, GA. We analyzed the data with zero-inflated Poisson model to assess the relationship between the barometric pressure, temperature, and daily stroke hospitalization. The results showed that there was a significantly correlation between daily barometric pressure variation and daily stroke hospitalization, especially on elder male patients (≥ 65). Stroke events were more likely to occur in the patients with risk factors than in those without risk factors when exposed to barometric pressure and temperature changes. Decreased barometric pressure and increased temperature were associated with increased daily stroke hospitalization. Furthermore, there was a potential delayed effect of increased stroke events after cold temperature exposure. Barometric pressure and temperature changes over the preceding 24 h are associated with daily stroke hospitalization. These findings may enhance our understanding of relationship between stroke and weather and maybe used in the development of public health strategies to minimize the weather-related stroke risk.