Three steroid-binding globulins, their localization in the brain and nose, and what they might be doing there.

Steroid-binding globulins (SBGs) such as sex hormone binding globulin, corticosteroid binding globulin, and vitamin-D binding protein are receiving increasing notice as being actively involved in steroid actions. This paper reviews data of all three of these SBGs, focusing on their presence and possible activity in the brain and nose. We have found all three proteins in the brain in limbic areas such as the paraventricular (PVN) and supraoptic nuclei (SON) as well as other areas of the hypothalamus, hippocampus, and medial preoptic area. There is also evidence that all three are made in the PVN and SON, in conjunction with the neuropeptides oxytocin and vasopressin. The localization of these three SBGs is more variable within areas of the main olfactory area and the vomeronasal organ. However, all three are found in the mucus of these areas, suggesting that one of their functions is to sequester aerosol steroids, such as pheromones, and deliver them to sensory cells and then to deeper sensory areas. In this manuscript, we present multiple models of SBG action including: A) SBG binding to a membrane receptor, B) this SBG receptor being associated with a larger protein complex including cytoplasmic steroid receptors, C) when the SBGs binds to their SBG receptors, second messengers within the cells respond, D) after SBG binding to its receptor, it releases its associated steroid into the membrane's lipid bilayer, from which it gains access into the cell only when bound by an internal protein, E) the SBG, possibly with its bound SBG receptor, is internalized into the cell from which it can gain access to numerous organelles and possibly the cell's nucleus or F) associate with intracellular steroid receptors, G) SBGs produced in target cells are released from those cells upon specific stimulation, and H) according to the Free Steroid Hypothesis steroids released from the extracellular SBG passively diffuse across the plasma membrane of the cell. These models move the area of steroid endocrinology forward by providing important paths of steroid activity within many steroid target cells.

Reconfigurable infrared hyperbolic metasurfaces using phase change materials.

Metasurfaces control light propagation at the nanoscale for applications in both free-space and surface-confined geometries. However, dynamically changing the properties of metasurfaces can be a major challenge. Here we demonstrate a reconfigurable hyperbolic metasurface comprised of a heterostructure of isotopically enriched hexagonal boron nitride (hBN) in direct contact with the phase-change material (PCM) single-crystal vanadium dioxide (VO2). Metallic and dielectric domains in VO2 provide spatially localized changes in the local dielectric environment, enabling launching, reflection, and transmission of hyperbolic phonon polaritons (HPhPs) at the PCM domain boundaries, and tuning the wavelength of HPhPs propagating in hBN over these domains by a factor of 1.6. We show that this system supports in-plane HPhP refraction, thus providing a prototype for a class of planar refractive optics. This approach offers reconfigurable control of in-plane HPhP propagation and exemplifies a generalizable framework based on combining hyperbolic media and PCMs to design optical functionality.

Voluntary intake and digestibility by sheep of alfalfa ensiled at different moisture concentrations following fertilization with dairy slurry.

Dairy slurry is used commonly as an animal-sourced fertilizer in agronomic production. However, residual effects of slurry application on intake and digestibility of alfalfa (Medicago sativa L.) silage from subsequent harvests are not well known. The objective of this study was to determine if moisture concentration of alfalfa silage and timing of dairy slurry application relative to subsequent harvest affected intake and digestibility by sheep. Katahdin crossbred ewes (n = 18; 48 ± 5.3 kg) in mid-gestation were stratified by BW and allocated randomly in each of two periods to one of six treatments arranged in a two × three factorial arrangement. Treatments consisted of recommended (RM; 46.8%) or low (LM; 39.7%) moisture at baling after either no slurry application (NS), slurry application to stubble immediately after removal of the previous cutting (S0), or slurry application 14 d after removal of the previous cutting (S14). Silages were chopped through a commercial straw chopper, packed into plastic trash cans, and then offered to ewes within 4 d of chopping. Period 1 of the intake and digestion study consisted of a 14-d adaptation followed by a 7-d fecal collection period. Period 2 followed period 1 after a 4-d rest and consisted of an 11-d adaptation followed by 7 d of fecal collection. Ewes were housed individually in 1.4 × 4.3-m pens equipped with rubber mat flooring. Feces were swept from the floor twice daily, weighed, and dried at 50 °C. Ewes had ad libitum access to water and were offered chopped silage for a minimum of 10% refusal (DM). Blood samples were collected immediately prior to feeding, and 4 and 8 h after feeding on the day prior to the end of each period. Organic matter intake (g/kg BW) and OM digestibility tended (P < 0.10) to be, and digestible OM intake (g/kg BW) was reduced by slurry application. Lymphocytes (% of total white blood cells) were greater (P < 0.05) from LM vs. RM and from NS vs. S0 and S14. Red blood cell concentrations were greater (P < 0.05) from S14 vs. S0 and from S0 and S14 vs. NS. Serum urea N concentrations did not differ (P > 0.17) across treatments. Therefore, moisture concentration of alfalfa silage within the range used in this study may not affect voluntary intake or digestibility, but slurry application may have an effect on digestible OM intake. Also, moisture concentration of alfalfa silage and time of dairy slurry application may affect specific blood hemograms.

Feeding distillers' grains, soybean hulls, or a mixture of both to cows as a forage replacement: Effects on intake, digestibility, and ruminal fermentation characteristics.

Coproduct feedstuffs offer a unique and potentially profitable avenue for cattle feeding strategies. However, research is lacking in the evaluation of varying coproducts on ruminal fermentation and digestive characteristics when included as the major component of the diet of cows. Our objective was to determine the effect of coproduct feedstuffs as a forage replacement on digestive and fermentative characteristics of cows. Eight ruminally fistulated cows (672 ± 32.0 kg initial BW and approximately 9 yr of age) were stratified by BW and randomly allocated to 1 of 4 diets (2 cows∙diet∙period) in a 2-period study: soybean hulls (SH), distillers' dried grains with solubles (DG), an isoenergetic mixture of soybean hulls and distillers' dried grains with solubles (MX), or ad libitum hay plus 0.9 kg/d of an isoenergetic mixture of soybean hulls and distillers' dried grains with solubles (HY). Diets were formulated to meet the ME requirements of a similar, companion study. Coproduct amounts were increased over a 14-d period. This was followed by a 14-d adaptation to diet and facilities and 5 d of total fecal collections. On the final day of fecal collections, rumen fluid was sampled immediately prior to feeding and 2, 4, 6, 8, 10 and 12 h after feeding for measurement of rumen VFA and ammonia concentrations. Intake of DM and OM was not different ( ≥ 0.28) among treatments, but digestibilities of DM, OM, NDF, and ADF were improved ( < 0.05) by coproduct feeding and by MX vs. the mean of SH and DG. Ruminal DM and OM fill were greater ( < 0.05) for cows offered HY than for cows offered the coproduct diets, greater for cows offered SH than for cows offered DG, and for the mean of SH and DG vs. MX. Ruminal retention time was greater ( < 0.05) for HY vs. the coproduct diets and for SH vs. DG. Apparent N absorption tended ( < 0.10) to be greater for cows offered the coproduct diets than for cows offered HY and greater for cows offered DG than for cows offered SH. Total VFA averaged across sampling times were greatest ( < 0.05) for cows offered SH, and ruminal ammonia N was greatest ( < 0.05) for cows offered either DG or MX at all sampling times. Based on these data, coproduct feedstuffs may be fed to meet the energy requirement of cows without negative effects on digestion or ruminal fermentation.

Estradiol's interesting life at the cell's plasma membrane.

Clearly, we have presented here evidence of a very complex set of mechanisms and proteins involved with various and intricate actions of steroids at the plasma membrane. Steroids do MUCH more at the plasma membrane than simply passing passively through it. They may sit in the membrane; they are bound by numerous proteins in the membrane, including ERs, SHBG, steroid-binding globulin receptors, and perhaps elements of cellular architecture such as tubulin. It also seems likely that the membrane itself responds graphically to the presence of steroids by actually changing its shape as well, perhaps, as accumulating steroids. Clara Szego suggested in the 1980s that actions of E2 at one level would act synergistically with its actions at another level (e.g. membrane actions would complement nuclear actions). Given the sheer number of proteins involved in steroid actions, just at the membrane level, it seems unlikely that every action of a steroid on every potential protein effector will act to the same end. It seems more likely that these multiple effects and sites of effect of steroids contribute to the confusion that exists as to what actions steroids always have. For example, there is confusion with regard to synthetic agents (SERMs etc.) that have different and often opposite actions depending on which organ they act upon. A better understanding of the basic actions of steroids should aid in understanding the variability of their clinical effects.

Effects of forage species and poultry litter application timing on forage preference by horses.

Bermudagrass ( L.) is a familiar forage in the equine industry and teff () is gaining popularity as well. However, it is unclear if the application of poultry litter as a fertilizer affects palatability of these forages in horses. Therefore, the objective of this study was to determine if forage species and timing of litter application as a fertilizer has an effect on preference by horses. Hay treatments were arranged in a 2 × 3 factorial treatment arrangement consisting of teff and bermudagrass harvested after no poultry litter application (NL), poultry litter applied to stubble immediately after removal of the previous cutting (L0), or poultry litter applied 14 d after the previous cutting (L14). Mature, stock-type geldings ( = 5; 480 ± 52.9 kg) were used in this study arranged as a balanced incomplete block design. Horses were offered different combinations of 4 of the 6 total forages daily for 3 d in each of 3 evaluation periods that immediately followed a 10-d adaptation period. Each forage was offered at half of the total daily DMI as measured during the last 5 d of the 10-d adaptation period to encourage selection among the 4 forages. Each hay offered was randomly allocated to a corner and suspended in hay nets over muck buckets in the corners of each stall. Horses were individually housed in 3.6- by 3.6-m indoor stalls with sand bedding and access to 3.6- by 7.6-m outdoor runs. Along with hay, horses were offered oats twice daily at 0.125% of BW at each feeding. Dry matter intake was greater ( < 0.01) for bermudagrass than for teff and for NL and L0 treatments compared with L14 treatments. Horses spent more ( < 0.01) time consuming bermudagrass compared with teff. However, there were no differences ( ≥ 0.25) in time spent consuming hay across litter treatments. Therefore, horses may prefer bermudagrass to teff and later application of poultry litter may affect voluntary intake by horses. However, all forages were mature, which may have impacted total intake and preference.

An active role for steroid-binding globulins: an update.

It has been 7 years (can it really be that long?) since we co-edited a volume (#38) of Hormone and Metabolic Research that focused on evidence that steroid-binding globulins play an active role in the actions of steroids. There has been considerable progress in identifying the location, the physiological actions, and of determining the role of binding globulins in the actions of steroids and identifying a membrane-associated receptor for a binding protein since then and this review will discuss this progress.

Performance by spring and fall-calving cows grazing with full, limited, or no access to toxic Neotyphodium coenophialum-infected tall fescue.

Replacing toxic, wild-type Neotyphodium coenophialum-infected tall fescue (E+) with nontoxic, N. coenophialum-infected tall fescue (NE+) has improved cow performance, but producer acceptance of NE+ has been slow. The objective was to compare performance by spring- and fall-calving cows grazing either E+ or NE+ at different percentages of the total pasture area. Gelbvieh×Angus crossbred cows (n=178) were stratified by BW and age within calving season and allocated randomly to 1 of 14 groups representing 5 treatments for a 3-yr study: i) Fall-calving on 100% E+ (F100); ii) Spring-calving on 100% E+ (S100); iii) Fall-calving on 75% E+ and 25% NE+ (F75); iv) Spring-calving on 75% E+ and 25% NE+ (S75); and v) Spring-calving on 100% NE+ (SNE100). Groups allocated to F75 and S75 grazed E+ until approximately 28 d before breeding and weaning, then were then moved to their respective NE+ pasture area for 4 to 6 wk; those allocated to F100, S100, and SNE100 grazed their pastures throughout the entire year. Samples of tall fescue were gathered from specific cells within each pasture at the time cows were moved into that particular cell (∼1 sample/mo). Blood samples were collected from the cows at the start and end of the breeding season. Stocking rate for each treatment was 1 cow/ha. Forage IVDMD, CP, and total ergot alkaloid concentrations were affected (P<0.05) by the treatment×sampling date interaction. Hay offered, cow BW, and BCS at breeding, end of breeding, and at weaning were greater (P<0.05) from fall-calving vs. spring-calving. Cow BW at weaning was greater (P<0.05) from F75 and S75 vs. F100 and S100. The calving season×NE+ % interaction affected (P<0.05) calving rates. Preweaning calf BW gain, actual and adjusted weaning BW, ADG, sale price, and calf value at weaning were greater (P<0.05) from fall-calving vs. spring-calving and from SNE100 vs. S75 except for sale price which was greater (P<0.05) from S75 vs. SNE100. Cow concentrations of serum prolactin at breeding and serum NEFA at the end of breeding were affected (P<0.05) by the calving season×NE+ % interaction. Serum Zn and Cu concentrations from cows were affected (P<0.05) by calving season. A fall-calving season may be more desirable for cows grazing E+, resulting in greater calving rates, cow performance, and calf BW at weaning, whereas limited access to NE+ may increase calving rates, serum prolactin, and NEFA concentrations during certain times in the production cycle, particularly in spring-calving cows.

Colocalization of p450 aromatase and oxytocin immunostaining in the rat hypothalamus.

With combined immunoperoxidase and immunofluorescence, we observed colocalization of cytochrome P450 aromatase with the posterior lobe peptide oxytocin and its associated neurophysin 1 in adult male rats. P450 was most abundant in the anterior hypothalamus. Colocalization of OT with P450 was observed in the preoptic region, the periventricular nucleus of the hypothalamus, the lateral subcommissural nucleus, and in the zona incerta. Magnocellular perikarya in the supraoptic and in the paraventricular nuclei contained only occasionally both antigens. P450 immunostaining overlapped to a great extent with known estrogen target regions. Oxytocinergic functions are controlled by estradiol while androgen receptors are mostly absent in neuroendocrine hypothalamic nuclei. Our findings suggest that systemic androgens may be aromatized to estrogens in male oxytocinergic neurons linked to the limbic system.

Pitch-dependent resonances and near-field coupling in infrared nanoantenna arrays.

We investigate coupling in arrays of nanoparticles resonating as half-wave antennas on both silicon and sapphire, and find a universal behavior when scaled by antenna length and substrate index. Three distinct coupling regimes are identified and characterized by rigorous finite-difference time domain simulations. As interparticle pitch is reduced below the oft-described radiative to evanescent transition, resonances blue shift and narrow and exhibit an asymmetric band consistent with a Fano lineshape. Upon further pitch reduction, a transition to a third regime, termed here as near-field coupling, is observed in which the resonance shifts red, becomes more symmetric, and broadens dramatically. This latter regime occurs when the extension of the resonant mode beyond the physical antenna end overlaps that of its neighbor. Simulations identify a clear rearrangement of field intensity accompanying this regime, illustrating that longitudinal modal fields localize in the air gap rather than in the higher index substrate at a pitch consistent with the experimentally observed transition.

Bilayer graphene grown on 4H-SiC (0001) step-free mesas.

We demonstrate the first successful growth of large-area (200 × 200 µm(2)) bilayer, Bernal stacked, epitaxial graphene (EG) on atomically flat, 4H-SiC (0001) step-free mesas (SFMs) . The use of SFMs for the growth of graphene resulted in the complete elimination of surface step-bunching typically found after EG growth on conventional nominally on-axis SiC (0001) substrates. As a result heights of EG surface features are reduced by at least a factor of 50 from the heights found on conventional substrates. Evaluation of the EG across the SFM using the Raman 2D mode indicates Bernal stacking with low and uniform compressive lattice strain of only 0.05%. The uniformity of this strain is significantly improved, which is about 13-fold decrease of strain found for EG grown on conventional nominally on-axis substrates. The magnitude of the strain approaches values for stress-free exfoliated graphene flakes. Hall transport measurements on large area bilayer samples taken as a function of temperature from 4.3 to 300 K revealed an n-type carrier mobility that increased from 1170 to 1730 cm(2) V(-1) s(-1), and a corresponding sheet carrier density that decreased from 5.0 × 10(12) cm(-2) to 3.26 × 10(12) cm(-2). The transport is believed to occur predominantly through the top EG layer with the bottom layer screening the top layer from the substrate. These results demonstrate that EG synthesized on large area, perfectly flat on-axis mesa surfaces can be used to produce Bernal-stacked bilayer EG having excellent uniformity and reduced strain and provides the perfect opportunity for significant advancement of epitaxial graphene electronics technology.

Effect of herbage depletion on short-term foraging dynamics and diet quality of steers grazing wheat pastures.

Two complementary experiments were completed to assess short-term foraging dynamics, diet quality, and ruminal degradation kinetics of herbage consumed by steers with 3 levels of herbage depletion. Experiment 1 was a behavioral study in which 2 ruminally cannulated steers were allocated to grazing scenarios simulating 3 levels of herbage depletion. These treatments included an ungrazed sward (control), as well as medium and high levels of herbage depletion. Grazing scenarios were sampled for sward surface height and amount of green leaf and stem before being grazed. Foraging dynamics were determined through measurements of bite rate, bite depth, eating step rate, eating distance, potential area consumed while grazing, and bites and intake per eating step. Also, quality of potential herbage consumed was estimated from hand-plucked herbage. In Exp. 2, ruminal degradation kinetics of DM for samples of herbage consumed (masticate) by steers during Exp. 1 were assessed in situ using 5 ruminally cannulated steers. The immediately soluble, degraded, and undegraded DM fractions were determined. The DM disappearance rate and lag times were determined from a nonlinear regression model, and the effective degradability of DM was calculated. Herbage depletion resulted in increased eating steps/minute, as well as the potential area harvested while grazing (P < 0.05) and reduced herbage intake/eating step (P < 0.05). Neither the herbage potentially consumed nor the ruminal degradation kinetics was affected by extent of depletion (P > 0.05). Under these experimental conditions, steers adapted their foraging dynamic and were able to sustain diet quality in the short term. These results imply that behavioral adaptations would make diet quality less sensitive to certain levels of herbage depletion.

Identification of sex hormone binding globulin-interacting proteins in the brain using phage display screening.

The present study reports the identification of human sex hormone binding globulin (SHBG)-interacting proteins in the brain using a phage display-based screening technology. Phage display is a system in which a foreign protein is displayed on the surface of a bacteriophage as a fusion protein with one of the coat proteins of the bacteriophage. T7 phage clones expressing normal human brain proteins (human normal brain phage-display cDNA expression library) were screened using SHBG as bait. The bound phage clones were then identified by DNA sequencing and by BLAST search analysis. Of the twenty binding proteins analyzed, three were found to be membrane-associated proteins: synaptosomal associated protein 25 (SNAP25), Thy-1 cell surface antigen and zonadhesin. Further studies will determine if the interactions of SHBG with these proteins have any role in the internalization and cell signaling events or whether they contribute to steroid delivery to specific cells.

Comparison of bloat potential between a variety of soft-red versus a variety of hard-red winter wheat forage.

Some aspects of wheat pasture bloat have been researched extensively, but few studies have evaluated the effect of wheat type or variety on bloat. Eight Gelbvieh x Angus ruminally cannulated heifers (515 +/- 49 kg of BW) and 48 Angus heifers (238 +/- 12 kg of BW) grazed 1-ha pastures of hard-red or soft-red winter wheat (Triticum aestivum L.) to evaluate the effect of wheat variety on bloat potential. In Exp. 1, cattle grazed from November 11 to 22 and from November 26 to December 7, 2006, in a crossover design. In Exp. 2, cattle were shrunk for 20 h and then grazed from December 19 to 20, 2006, and from January 19 to 20, 2007. In both experiments, bloat was scored at 1000 and 1600 h daily. Rumen samples were collected at 0600, 1200, and 1800 h during each of the last 2 d of each period in Exp. 1 and during both days of each period of Exp. 2. Rumen samples were evaluated for pH, foam production and strength, and viscosity. In Exp. 1, cannulated heifers grazing soft-red had a greater (P < 0.01) percentage of observed bloat (21.9 vs. 5.6%) than those grazing hard-red winter wheat, but bloat incidence was low (2.1%) for the stocker cattle, with no difference between hard-red and soft-red winter wheat (P = 0.52). Viscosity of the rumen fluid was affected (P = 0.03) by the wheat variety x time interaction, with soft-red at 1200 and 1800 h being more viscous than soft-red at 0600 h and hard-red at all times. Foam strength, as determined by bubbling CO(2) gas through rumen fluid, had a wheat variety x time interaction (P = 0.02) with both wheat varieties similar at 0600 h but soft-red having greater foam strength at 1200 and 1800 h. In Exp. 2, no bloat was observed, and no differences between wheat varieties were observed for any of the rumen foam measures. Therefore, for these 2 varieties, the soft-red winter wheat had a greater bloat potential than the hard-red winter wheat based on results from the cannulated heifers, but no differences were observed in the frequency of bloat in stocker cattle. In this study, shrinking of cattle before grazing wheat pasture did not induce bloat.

Sex hormone binding globulin and aging.

New and more active concepts of steroid binding globulin action are emerging from recent research. As a result, examination of steroid levels in aging humans and the role of steroid binding globulins need to be re-visited. This review will discuss the possibility that sex hormone binding globulin (SHBG) plays an active role in the aging process. It will discuss the changes in blood levels of SHBG in aging humans in association with sexual activity, prostate hypertrophy and cancer, uterine leiomyoma, breast cancer, obesity and particularly the relationship between SHBG and HDL-cholesterol, Alzheimer's disease, osteoporosis, and cardiovascular disease. Starting with the idea that SHBG is an active participant in steroid action demands a re-evaluation of data demonstrating a primary change in blood SHBG levels in association with various pathologies. Here we discuss the postulate that SHBG may act at its own receptor at the plasma membrane level to influence other receptors such as scavenger receptors and HDL-cholesterol receptors. We will also suggest that SHBG is a critical marker for mating and thus may be an important physiological molecule in control of aging.

Internalization of sex hormone-binding globulin into neurons and brain cells in vitro and in vivo.

BACKGROUND: Sex hormone-binding globulin (SHBG) is a 94-kDa homodimer that binds steroids and is made in the hypothalamus. We have demonstrated that infusions of SHBG into the hypothalami of rats increase their female sexual receptivity except when SHBG is coupled to dihydrotestosterone (DHT) suggesting that SHBG has an active function in behavioral neuroendocrinology. METHODS: This study examines the possibility that SHBG is internalized by neuronal and/or non-neuronal brain cells as one possible mode of action using in vitro and in vivo techniques. RESULTS: First, analysis of the uptake of radiolabeled SHBG ((125)I-SHBG) found (125)I-SHBG uptake in HT22 hippocampal cells stably transfected with cDNA for ER beta (HT22-ER beta). The addition of DHT to (125)I-SHBG significantly inhibited (125)I-SHBG uptake in HT22-ER beta cells but not in HT22-ER alpha or HT22 wild-type cells. SHBG internalization was specific as it did not occur in either the human neuroblastoma cell line SK-N-SH or the glioma cell line C6. Second, SHBG was labeled with a fluor (Alexa-555), and infused into the lateral cerebroventricles of ovariectomized rats. Optimal SHBG uptake was seen 10 min after these infusions. SHBG uptake was seen in specific parts of the choroid plexus and periventricular cells as well as into cells in the paraventricular nucleus, the medial forebrain bundle, and the habenula. CONCLUSIONS: These studies suggest that SHBG is internalized by brain cells, which may be affected by the presence of ER beta. The gonadal steroids have numerous effects in brain and the discovery that the steroid-binding protein SHBG is taken up into neurons and brain cells may demand a change in thinking about how steroids are delivered to brain cells to affect neurophysiology.

Expression of corticosteroid binding globulin in the rat central nervous system.

Immunoreactivity for corticosteroid binding globulin was observed in the hypothalamus of intact male rats in the magnocellular nuclei and in single neurons in the periventricular nucleus and the lateral hypothalamus. The suprachiasmatic and the arcuate nuclei contained parvocellular neurons with specific immunoreactivity. Extensive networks of immunopositive fibers were observed in the lateral hypothalamus, the preoptic region, the bed nucleus of the stria terminalis and along the third ventricle. Immunostained axons often exhibited varicosities. The internal and the external layer of the median eminence showed numerous bundles of immunostained axons. Herring bodies in the posterior pituitary lobe contained specific immunoreactivity while pituicytes remained unstained. A portion of the Purkinje cells in the cerebellum and mossy fibers in the cerebellar granular layer stained for corticosteroid binding globulin. Some of the pyramidal cells in the hippocampus were corticosteroid binding globulin positive. Immunostained fibers occurred in the mesencephalon in the periaqueductal grey and in the medulla oblongata. A small fraction of the ependymal cells was also stained. In the spinal cord we observed specific immunoreactivity in a portion of the neurons in the dorsal horn. With polymerase chain reaction we confirmed the presence of the respective transcripts in the different brain regions. The multiple locations of corticosteroid binding globulin throughout the central nervous system suggest multiple functional properties, including neuroendocrine and neurohumoral functions.

Changes of sex hormone-binding globulin/SHBG expression in the hypothalamo-hypophyseal system of rats during pregnancy, parturition and lactation.

Sex hormone-binding globulin (SHBG) is expressed in hypothalamic magnocellular neurons. High co-localization rates of SHBG with oxytocin have been observed in the hypothalamus, indicating that SHBG plays a role in pregnancy, parturition and lactation. Further studies have shown that hypothalamic SHBG expression is malleable to changing steroid conditions. In this study, we have examined SHBG levels in the supraoptic and paraventricular hypothalamic nuclei and in the posterior pituitary lobe of late pregnant, parturient and early lactating rats by IN SITU hybridization, immunocytochemistry, and ELISA. Immunocytochemical and biochemical analysis showed that the SHBG levels increased during late pregnancy in hypothalamic nuclei. During parturition, SHBG levels fell in the magnocellular nuclei but increased in the posterior pituitary lobe. SHBG levels increase again during lactation. At day six of lactation, there was no significant difference in SHBG levels compared to normal cycling female rats, which served as control in this study. IN SITU hybridization showed increased SHBG mRNA signal during late pregnancy. The highest SHBG expression was observed during parturition. Our data indicate that hypothalamic SHBG expression changes during pregnancy, parturition and lactation, parallel to ovarian steroid and co-localized OT levels. This may in part be linked to known steroid actions on synthesis and secretion of magnocellular hypothalamic peptide hormones, important for the control of parturition and lactation.