Presence of synaptonemal complex protein 1 transversal filament-like protein in human primary spermatocytes

The synaptonemal complex (SC) is involved in the pairing of chromosomes during meiosis. We found that antibodies raised against a protein component (P1) of the mouse synaptonemal complex, mouse SCP1, also identified the SC in human primary spermatocytes. Biopsies from 18 men presented with infertility were evaluated by light-field microscopy and grouped into five categories: normal spermatogenesis, Sertoli cell-only syndrome, meiotic disturbances, spermiogenic (i.e. differentiation) disturbances, and other combined disturbances. In all the normal subjects the SCP1 antibody distinctly stained the synaptonemal complexes of primary spermatocytes, whereas Sertoli cells, spermatogonia or spermatids were never stained. In three of the groups, which had germ cells but showed spermatogenic disturbances, the staining was similar to that seen in normal subjects. In sharp contrast to this, in sections from men with Sertoli cell-only syndrome no specific staining was seen. This study demonstrates that a SCP1-related protein is also conserved in the synaptonemal complex in meiotic cells from man. Further studies will reveal to what extent the absence or the non-functionality of SCP1 contributes to male infertility.      

Anabolic and catabolic hormonal response of elite runners to training at high altitude

A 2-week training period 2000 meters above sea level performed by 6 male elite Swedish runners influenced neither basal anabolic (total and non-sex hormone-binding globulin (SHBG)-bound testosterone (NST) and insulin-like growth factor-1 (IGF-1) nor catabolic (cortisol) hormones when comparing serum levels prior to and after the training camp. The anabolic vs catabolic hormone balance, expressed as the NST: cortisol ratio, also remained unchanged as well as SHBG and body mass. Thus, training at 2000 meters above sea level, often practised by elite runners to improve performance in competition at sea level, does not result in a catabolic situation after return to sea level, as measured by peripheral hormones. However, the adaptation to high altitude was associated with a slight (NS) decrease in testosterone as well as in anabolic vs catabolic balance as measured the third day at high altitude. Simultaneously, a decrease in subjective performance was claimed by the runners, but could not be shown by objective measurements. From day 3 to day 9 at high altitude, all runners claimed a subjective recuperation of performance. Total and non-SHBG-bound testosterone increased significantly from day 3 at high altitude to the first post-camp sea-level test. The results reflect the necessity of adaptation when travelling to races at different altitudes. The Swedish runners had significantly higher cortisol, total testosterone and NST levels compared with basal values of a group of 17 elite Kenyan runners living and training at high altitude. Since the NST cortisol and IGF-1 values were not lower, a catabolic state or malnutrition was not likely to be present. The results might reflect an adaptation to altitude or ethnic variations.     

Estrogens affect endothelin-1 mRNA expression in LNCaP human prostate carcinoma cells

OBJECTIVE: To study effects of estrogens on endothelin-1 (ET-1) mRNA expression in the androgen-sensitive LNCaP-FGC cell line and its androgen-resistant derivative LNCaP-r. Further, if effects of estrone sulfate (E1S) are mediated via conversion to estradiol-17beta (E2). Estrogens have been shown to down-regulate ET-1, a mediator of the osteoblastic response of bone to metastatic prostate cancer.METHODS: Cells were grown in steroid-depleted medium and incubated for 2-4 and 48 hours with 0, 1, 10, and 100 nM of either E1S or E2. mRNA levels were measured with an RT-PCR technique. Estrogen metabolism by LNCaP-FGC cells was studied by incubation with estrone (E1) and E1S at the same conditions, followed by determination of E1 and E2.RESULTS: ET-1 mRNA expression in LNCaP-FGC cells was significantly suppressed by E2 and E1S following incubation for 2-4h but after 48 h only by E2 at 1 and 10nM and in LNCaP-r cells only by E2 at 100 nM following 2-4h of incubation. ET-1 mRNA expression was significantly higher in untreated LNCaP-r than in untreated LNCaP-FGC cells. E1 was efficiently transformed into E2 by LNCaP-FGC cells but very little to E1 and no E2 was formed from E1S.CONCLUSION: ET-1 mRNA expression in LNCaP-FGC can be inhibited by E2, but also by its prehormone E1S. The lack of formation of E2 from E1S suggests a mode of action not related to classical steroid receptors. The higher level of ET-1 mRNA expression found in LNCaP-r cells may reflect the capability of a hormone refractory tumor to maintain activity on its own, independently of known regulatory mechanisms such as sex steroids.     

Increasing fecal butyrate in ulcerative colitis patients by diet: controlled pilot study

Topical butyrate has been shown to be effective in the treatment of ulcerative colitis (UC). Butyrate is derived from colonic fermentation of dietary fiber, and our aim was to study whether UC patients could safely increase the fecal butyrate level by dietary means. We enrolled 22 patients with quiescent UC (mean age, 44 years; 45% women; median time from last relapse, 1 year) in a controlled pilot trial lasting 3 months. The patients were instructed to add 60 g oat bran (corresponding to 20 g dietary fiber) to the daily diet, mainly as bread slices. Fecal short-chain fatty acids (SCFAs) including butyrate, disease activity, and gastrointestinal symptoms were recorded every 4 weeks. During the oat bran intervention the fecal butyrate concentration increased by 36% at 4 weeks (from 11 +/- 2 (mean +/- SEM) to 15 +/- 2 micromol/g feces) (p < 0.01). The mean butyrate concentration over the entire test period was 14 +/- 1 micromol/g feces (p < 0.05). Remaining fecal SCFA levels were unchanged. No patient showed signs of colitis relapse. Unlike controls, the patients showed no increase in gastrointestinal complaints during the trial. Yet patients reporting abdominal pain and reflux complaints at entry showed significant improvement at 12 weeks that returned to baseline 3 months later. This pilot study shows that patients with quiescent UC can safely take a diet rich in oat bran specifically to increase the fecal butyrate level. This may have clinical implications and warrants studies of the long-term benefits of using oat bran in the maintenance therapy in UC.     

Regulation of matrix metalloproteinase 13 expression by androgen in prostate cancer

The matrix metalloproteinases (MMPs) are members of a family of endopeptidases that are able to degrade extra-cellular matrix. MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), play a key role in the migration of normal and malignant cell. Interaction of MMPs and TIMPs has been involved in the process of tumor invasion and metastasis. Using cDNA microarray as a screening tool to find androgen regulated gene in prostate cancer, we have found that expression of MMP-13 is regulated by androgen in prostate cancer derived cell line LNCaP. This regulation was further confirmed and quantified by real-time RT-PCR. In addition, the upregulation of MMP-13 mRNA by androgen could be abolished by the androgen antagonist Casodex but not the protein inhibitor cycloheximide. Western blot and immunohistochemistry of MMP-13 confirmed the androgen regulation at the protein level. We have furthermore shown that MMP-13 expression is presented in human prostate cancer obtained from aspiration biopsy. In summary, MMP-13 is androgen regulated and detectable in prostate cancer. Further study of MMP-13 in prostate cancer may help us to understand the progression of the cancer and can lead to new therapeutic options.     

The early luteal phase in successful and unsuccessful implantation after IVF-ET

The hormonal milieu at embryo implantation after in-vitro fertilization was investigated. Superstimulation was accomplished with clomiphene citrate and human menopausal gonadotrophin (HMG) injections followed by ovulation induction with human chorionic gonadotrophin (HCG). Venous blood samples were drawn on days 2 and 8, the day of oocyte recovery being day 0. Fifteen women with successful implantation, defined as an ultrasound-verified pregnancy, were compared to 42 women with unsuccessful implantation, using a three-way analysis of variance. Oestradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) did not differ between the two groups. However, the ratios of oestradiol/progesterone and of testosterone/SHBG were significantly higher in the non-fertile cycles, both on day 2 and on day 8 (P less than 0.05). Furthermore, there was a highly significant decrease in oestradiol, progesterone and testosterone between days 2 and 8 in fertile as well as in non-fertile cycles (P less than 0.001) and a highly significant increase in SHBG from day 2 to day 8 in both groups (P less than 0.001). The higher testosterone/SHBG ratio in the non-pregnant women implies a relative hyperandrogenicity in this group that might have adversely affected the uterine receptivity.     

Sex hormone-binding globulin, oestradiol-17 beta, progesterone and testosterone at stimulation and after embryo transfer during in-vitro fertilization.

Serum concentrations of sex hormone-binding globulin (SHBG), oestradiol-17 beta progesterone and testosterone were measured in 23 gonadotrophin-stimulated menstrual cycles and in the implantation period [days 11-19 after human chorionic gonadotrophin (HCG) injection] following in-vitro fertilization and embryo transfer. Nine cycles resulted in successful pregnancies, one pregnancy ended in spontaneous abortion (week 14) and 13 cycles were without conception. SHBG levels were significantly elevated above pretreatment values from day 3 after HCG injection onwards. A significant positive correlation was found between increments in SHBG (delta SHBG) during the luteal phase and oestradiol/testosterone ratios during the follicular and luteal phases. In the pregnant cycles a significant positive correlation was also found between delta SHBG during the implantation period and oestradiol/testosterone ratios during the luteal phase and the implantation period. Significant negative correlations were found between delta SHBG and testosterone during the luteal phase in pregnant and non-pregnant women as well as between delta SHBG during the period corresponding to implantation and testosterone during the luteal phase in non-pregnant cycles. The results may reflect a modulating action of the oestrogen/androgen balance upon SHBG levels in subjects with supraphysiological oestradiol levels, such as in stimulated cycles and in very early pregnancy.     

Placental protein 14 in human in-vitro fertilization early pregnancies.

Placental protein 14 (PP14) and human chorionic gonadotrophin (HCG) were analysed in patients participating in an in-vitro fertilization-embryo transfer programme which did not include any kind of luteal support. Women with normal pregnancies, spontaneous abortions, ectopic pregnancies, biochemical pregnancies and non-pregnant women were compared. A combination of HCG and PP14 analyses distinguished between normal and abnormal implantation as early as 15 days after oocyte retrieval. The product of HCG (IU/l) and PP14 (micrograms/l) concentrations differed significantly between normal pregnancy, spontaneous abortion and ectopic pregnancy (P = 0.0248). It is concluded that both endometrial (PP14) and trophoblastic (HCG) markers, when used in combination, exhibit changes in abnormal implantation which may be clinically useful.     

Occupational trajectories of working conditions in Sweden: Development trends in the workforce, 1997–2015

Objective:This study aimed to explore the development of working conditions within and between occupations in the Swedish labor market from 1997 to 2015 and whether any polarization in working conditions concurrently occurred between occupations.Methods:Cross-sectional data from ten waves of the Swedish Work Environment Surveys (1997–2015) were used and an aggregated occupational-level dataset was created using the Swedish Standard Classification of Occupations. To capture the patterns of change in working conditions over time (ie, growth), growth curve modeling was used to identify the starting points for 89 occupations (intercepts) as well as both the shape (functional form) and rate of growth (slope) over time.Results:The Swedish labor market was stable overall, with some small, mainly positive, changes in job demands and resources. Different occupations developed in divergent directions, but there was no evidence of polarization.Conclusions:The findings indicate that macro-level stability can hide highly heterogeneous patterns of change among different occupational groups. This type of analysis, taking context into account, could be valuable for decision makers intending to improve the work environment.