Dydrogesterone and norethisterone regulate expression of lipoprotein lipase and hormones-sensitive lipase in human subcutaneous abdominal adipocytes

Aim: In premenopausal women, hyper-androgenicity is associated with central obesity and an increased cardiovascular risk. We investigated the effects of dydrogesterone (DYD)(a non-androgenic progestogen) and norethisterone (NET)(an androgenic progestogen) on lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and glycerol release in adipocytes isolated from subcutaneous abdominal adipose tissue. Methods: Adipose tissue was obtained from 12 non-diabetic women, mean age 51 years (range 37-78) and mean BMI 25.4kg/m2 (range 20.3-26.4). Adipocytes were treated with increasing doses of DYD and NET for 48 hours prior to protein extraction. Effects on lipogenesis and lipolysis were assessed using western blotting to determine the expression of key enzymes, LPL (56kDa) and HSL (84kDa) respectively. Measurement of glycerol release into the medium provided an assessment of lipolytic activity. Results: Expression of LPL was increased by DYD and NET (mean protein expression relative to control ± SEM); with greatest effect at 10-8M for DYD: 2.32±0.51(p0.05). Conclusions: DYD and NET significantly increased LPL expression relative to control whilst significantly reducing HSL expression. At the concentrations studied, similar effects were observed with the androgenic NET and the non-androgenic DYD despite differing effects on the lipid profile when taken in combination with estrogen. Further work in this area may improve knowledge about the effects of different progestogens on body fat distribution and enable progestogen use to be tailored to the individual to achieve maximal benefits

Activation of the LH receptor up regulates the type 2 adiponectin receptor in human granulosa cells

PURPOSE: Adiponectin is a predominantly adipocyte-derived hormone which influences insulin sensitivity and energy homeostasis through at least two receptors, AdipoR1 and AdipoR2. In animal models, adiponectin may regulate ovarian steroidogenesis, folliculogenesis, and ovulation. The receptors AdipoR1 and AdipoR2 are present in the human ovary, but their regulation is unknown. In these studies, we determined the effects of LH receptor activation on the expression and function of the two adiponectin receptors in human granulosa cells. METHODS: Granulosa cells were obtained at the time of oocyte retrieval in women undergoing in vitro fertilization (IVF). Cells were isolated and cultured for 48 h in DMEM/F12 medium with 5 % FBS and 50 ug/ml gentamicin. Medium was changed to low serum for 12 h and cells were treated with hCG (100 ng/ml), forskolin (30 μMol/L), or FSH (1 IU/ml) for 24 h for mRNA experiments. mRNA was isolated and RT PCR was performed using Taqman assays and quantification with the delta delta CT method. For immunocytochemistry, cells were grown on chamber slides and treated with hCG for 1 to 24 h and fixed with acetone. ICC was performed with polyclonal rabbit primary antibodies followed by alexa fluor goat anti-rabbit antibody and imaging with a fluorescence microscope and Zeiss software analysis. 3β-hydroxysteroid dehydrogenase (3βHSD) enzyme activity was determined by measuring the progesterone produced when cells were provided with an excess of 22-hydroxy-cholesterol as substrate following an incubation with hCG (1 IU/ml) and/or adiponectin (10 ng/ml). Progesterone content in the media was determined by ELISA. RESULTS: Messenger RNA for the two Adiponectin receptors is differentially regulated by activation of LHR with hCG treatment. AdipoR2 was increased nearly 4-fold (p < 0.05), whereas AdipoR1 expression was not changed by hCG treatment. Treatment with either FSH or forskolin (an activator of cAMP) had similar effects. Basal AdipoR2 protein was fairly low in granulosa cells in culture however treatment of cells with hCG resulted in a discernible increase in immunodetectable cytoplasmic protein as early as 6 h after treatment and was maintained for at least 24 h. The number of cells positive for AdipoR2 at 6 h increased from a basal of 20 % to almost 60 % (p < 0.05). Adiponectin treatment of hCG-primed cells resulted in increased 3βHSD activity by approximately 60 % over hCG alone and more than 3-fold over basal levels. CONCLUSIONS: AdipoR2 is regulated by the LH receptor function via a cAMP dependant mechanism. Increased expression of adipoR2 prior to and following ovulation may contribute to enhanced 3βHSD activity and increased progesterone secretion by the corpus luteum of the ovary. Dysregulation of adiponectin that may occur with PCOS may impair normal progesterone production

Stress and immunological response of heifers divergently ranked for residual feed intake following an adrenocorticotropic hormone challenge

peer-reviewedBackground When an animal is exposed to a stressor, metabolic rate, energy consumption and utilisation increase primarily through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Changes to partitioning of energy by an animal are likely to influence the efficiency with which it is utilised. Therefore, this study aimed to determine the physiological stress response to an exogenous adrenocorticotropic hormone (ACTH) challenge in beef heifers divergently ranked on phenotypic residual feed intake (RFI). Results Data were collected on 34 Simmental weaning beef heifers the progeny of a well characterized and divergently bred RFI suckler beef herd. Residual feed intake was determined on each animal during the post-weaning stage over a 91-day feed intake measurement period during which they were individually offered adlibitum grass silage and 2 kg of concentrate per head once daily. The 12 highest [0.34 kg DM/d] and 12 lowest [−0.48 kg DM/d] ranking animals on RFI were selected for use in this study. For the physiological stress challenge heifers (mean age 605 ± 13 d; mean BW 518 ± 31.4 kg) were fitted aseptically with indwelling jugular catheters to facilitate intensive blood collection. The response of the adrenal cortex to a standardised dose of ACTH (1.98 IU/kg metabolic BW0.75) was examined. Serial blood samples were analysed for plasma cortisol, ACTH and haematology variables. Heifers differing in RFI did not differ (P = 0.59) in ACTH concentrations. Concentration of ACTH peaked (P < 0.001) in both RFI groups at 20 min post-ACTH administration, following which concentration declined to baseline levels by 150 min. Similarly, cortisol systemic profile peaked at 60 min and concentrations remained continuously elevated for 150 min. A RFI × time interaction was detected for cortisol concentrations (P = 0.06) with high RFI heifers had a greater cortisol response than Low RFI from 40 min to 150 min relative to ACTH administration. Cortisol response was positively associated with RFI status (r = 0.32; P < 0.01). No effect of RFI was evident for neutrophil, lymphocytes, monocyte, eosinophils and basophil count. Plasma red blood cell number (6.07 vs. 6.23; P = 0.02) and hematocrit percentage (23.2 vs. 24.5; P = 0.02) were greater for low than high RFI animals. Conclusions Evidence is provided that feed efficiency is associated with HPA axis function and susceptibility to stress, and responsiveness of the HPA axis is likely to contribute to appreciable variation in the efficiency feed utilisation of cattle

The Stellar Content of Obscured Galactic Giant H II Regions IV.: NGC3576

We present deep, high angular resolution near-infrared images of the obscured Galactic Giant H II region NGC3576. Our images reach objects to ~3M_sun. We collected high signal-to-noise K-band spectra of eight of the brightest objects, some of which are affected by excess emission and some which follow a normal interstellar reddening law. None of them displayed photospheric features typical of massive OB type stars. This indicates that they are still enshrouded in their natal cocoons. The K-band brightest source (NGC3576 #48) shows CO 2.3 micron bandhead emission, and three others have the same CO feature in absorption. Three sources display spatially unresolved H_2 emission, suggesting dense shocked regions close to the stars. We conclude that the remarkable object NGC3576 #48 is an early-B/late-O star surrounded by a thick circumstellar disk. A number of other relatively bright cluster members also display excess emission in the K-band, indicative of reprocessing disks around massive stars (YSOs). Such emission appears common in other Galactic Giant H II regions we have surveyed. The IMF slope of the cluster, Gamma = -1.51, is consistent with Salpeter's distribution and similar to what has been observed in the Magellanic Cloud clusters and in the periphery of our Galaxy.Comment: 14 pages, 11 figures, accepted for publication in A

A Multicriteria Assessment of Forage or Concentrate-Based Finishing Diets for Temperate Pasture-Based Suckler Beef Production Systems

This study evaluated the effect of contrasting ‘finishing’ diets on animal performance, meat nutritional value, land use, food-feed competition, farm economics and greenhouse gas (GHG) emissions in temperate pasture-based suckler weanling-to-steer beef systems. Post-weaning, eight-month-old, spring-born, late-maturing breed steers (333 kg) were assigned to one of three systems: (1) Grass silage + 1.2 kg concentrate DM (148 days), followed by pasture (123 days) and finished on ad libitum concentrates (120 days) - slaughter age, 21 months (GRAIN); (2) as per (1) but pasture (196 days) and finished on grass silage ad libitum + 3.5 kg concentrate DM (124 days) - slaughter age, 24 months (SIL+GRAIN); and (3) grass silage-only (148 days), pasture (196 days), silage-only (140 days) and finished on pasture (97 days) - slaughter age, 28 months (FORAGE). The mean target carcass weight was 390 kg for each system. Data generated was used to parameterise a farm-level beef systems model. Measured concentrate DM intake was 1187, 606 and 0 kg/head, and average daily gain was 0.83, 0.72 and 0.62 kg for GRAIN, SIL+GRAIN and FORAGE, respectively. Direct (pasture) land use was lowest for GRAIN. FORAGE was more profitable and was the only net producer of human edible protein and energy/ha. GRAIN produced the lowest GHG emissions per animal and meat essential amino acid concentration. FORAGE was more favourable for GHG emissions per kg of net (produced vs. consumed) production of human edible protein. Muscle amino acid and saturated fatty acid concentrations did not differ between the production systems, but FORAGE had the highest muscle concentration of omega-3 poly-unsaturated fatty acids. Differences in muscle mineral concentration were small. In conclusion, there are inverse relationships between food-feed competition, land-use, economics and GHG emissions per unit of product among different systems

LoCuSS : exploring the connection between local environment, star formation, and dust mass in Abell 1758

We explore the connection between dust and star formation, in the context of environmental effects on galaxy evolution. In particular, we exploit the susceptibility of dust to external processes to assess the influence of dense environment on star-forming galaxies. We have selected cluster Abell 1758 from the Local Cluster Substructure Survey (LoCuSS). Its complex dynamical state is an ideal test-bench to track dust removal and destruction in galaxies due to merger and accretion shocks. We present a systematic panchromatic study (from 0.15 mu m with GALEX to 500 mu m with Herschel) of spectroscopically confirmed star-forming cluster galaxies at intermediate redshift. We observe that the main subclusters (A1758N and A1758S) belong to two separate large-scale structures, with no overlapping galaxy members. Star forming cluster members are found preferentially outside cluster central regions, and are not isotropically distributed. Rather, these galaxies appear being funneled towards the main subclusters along separate accretion paths. Additionally, we present the first study of dust-to-stellar (DTS) mass ratio used as an indicator for local environmental influence on galaxy evolution. Star-forming cluster members show lower mean values (32 per cent at 2.4 sigma) of DTS mass ratio and lower levels of infrared emission from birth clouds with respect to coeval star-forming field galaxies. This picture is consistent with the majority of star-forming cluster members infalling in isolation. Upon accretion, star formation is observed to decrease and warm dust is destroyed due to heating from the intracluster medium radiation, ram-pressure stripping, and merger shocks.Peer reviewe

The very large G-protein coupled receptor VLGR1: a component of the ankle link complex required for the normal development of auditory hair bundles

Sensory hair bundles in the inner ear are composed of stereocilia that can be interconnected by a variety of different link types, including tip links, horizontal top connectors, shaft connectors, and ankle links. The ankle link antigen is an epitope specifically associated with ankle links and the calycal processes of photoreceptors in chicks. Mass spectrometry and immunoblotting were used to identify this antigen as the avian ortholog of the very large G-protein-coupled receptor VLGR1, the product of the Usher syndrome USH2C (Mass1) locus. Like ankle links, Vlgr1 is expressed transiently around the base of developing hair bundles in mice. Ankle links fail to form in the cochleae of mice carrying a targeted mutation in Vlgr1 (Vlgr1/del7TM), and the bundles become disorganized just after birth. FM1-43 [N-(3-triethylammonium)propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] dye loading and whole-cell recordings indicate mechanotransduction is impaired in cochlear, but not vestibular, hair cells of early postnatal Vlgr1/del7TM mutant mice. Auditory brainstem recordings and distortion product measurements indicate that these mice are severely deaf by the third week of life. Hair cells from the basal half of the cochlea are lost in 2-month-old Vlgr1/del7TM mice, and retinal function is mildly abnormal in aged mutants. Our results indicate that Vlgr1 is required for formation of the ankle link complex and the normal development of cochlear hair bundles

Analgesic Efficacy of Pfannenstiel Incision Infiltration with Ropivacaine 7.5 mg/mL for Caesarean Section

Background. Pain after Caesarean delivery is partly related to Pfannenstiel incision, which can be infiltrated with local anaesthetic solutions. Methods. A double- blind randomized control trial was designed to assess the analgesic efficacy of 7.5 mg/mL ropivacaine solution compared to control group, in two groups of one hundred and forty four parturients for each group, who underwent Caesarean section under spinal anaesthesia: group R (ropivacaine group) and group C (control group). All parturients also received spinal sufentanil (2.5 μg). Results. Ropivacaine infiltration in the Pfannenstiel incision for Caesarean delivery before wound closure leads to a reduction of 30% in the overall consumption of analgesics (348 550 mg for group R versus 504 426 mg for group C with P < .05), especially opioids in the first 24 hours, but also significantly increases the time interval until the first request for an analgesic (4 h 20 min ± 2 h 26 for group R versus 2 h 42 ± 1 h 30 for group C). The P values for the two groups were: P < .0001 for paracetamol, P < .0001 for ketoprofen and P for nalbuphine which was the most significant. There is no significant difference in the threshold of VAS in the two series. Conclusion. This technique can contribute towards a programme of early rehabilitation in sectioned mothers, with earlier discharge from the post-labour suite

NGC 3576 and NGC 3603: Two Luminous Southern HII Regions Observed at High Resolution with the Australia Telescope Compact Array

NGC 3576 (G291.28-0.71; l=291.3o, b=-0.7o) and NGC 3603 (G291.58-0.43; l=291.6o, b=-0.5o) are optically visible, luminous HII regions located at distances of 3.0 kpc and 6.1 kpc, respectively. We present 3.4 cm Australian Telescope Compact Array (ATCA) observations of these two sources in the continuum and the H90a, He90a, C90a and H113b recombination lines with an angular resolution of 7" and a velocity resolution of 2.6 km/s. All four recombination lines are detected in the integrated profiles of the two sources. Broad radio recombination lines are detected in both NGC 3576 (DV_{FWHM}>= 50 km/s) and NGC 3603 (DV_{FWHM}>=70 km/s). In NGC 3576 a prominent N-S velocity gradient (~30 km/s/pc) is observed, and a clear temperature gradient (6000 K to 8000 K) is found from east to west, consistent with a known IR color gradient in the source. In NGC 3603, the H90a, He90a and the H113b lines are detected from 13 individual sources. The Y^+ (He/H) ratios in the two sources range from 0.08+/-0.04 to 0.26+/-0.10. We compare the morphology and kinematics of the ionized gas at 3.4 cm with the distribution of stars, 10 micron emission and H_2O, OH, and CH_3OH maser emission. These comparisons suggest that both NGC 3576 and NGC 3603 have undergone sequential star formation.Comment: 24 pages, 12 Postscript figure