Sex hormones regulate ABR latency

OBJECTIVE: To examine various comfort measures and evaluate their effects in alleviating nipple soreness. DESIGN: Prospectively randomized, experimental study. SETTING: Postpartum unit of a community teaching hospital. PATIENTS: Seventy-three primiparous, postpartum, breastfeeding women. INTERVENTIONS: Subjects were randomly assigned to four groups, with all women receiving instruction about breastfeeding and using one of the following treatments: warm moist tea bag compress, warm water compress, expressed milk massaged into the nipple and areola and air dried, instruction only (control group). The subjects completed a questionnaire each morning for 7 days regarding nipple soreness. MAIN OUTCOME MEASURE: Effect of treatments on postpartum nipple pain. RESULTS: Subjects in the warm water compress group demonstrated significantly less pain on Day 3 than did the tea or breast milk group. CONCLUSIONS: Anticipatory guidance by obstetric nurses may assist breastfeeding women in treating their pain nonpharmacologically.     

Sex hormones and headache

A variety of evidence suggests a link between migraine and the female sex hormones. Women with migraine outnumber men by at least a 2:1 ratio and definite patterns of development and attacks are noted at menarche and throughout the period of menses, related to trimester of pregnancy, and again at menopause, although it may also regress. Hormonal replacement with estrogen can exacerbate migraine; oral contraceptives can change the character and frequency of migraine headache. This article will cover approaches to the therapy of hormone-related headaches associated with the menstrual cycle, menopause, and oral contraceptives.     

Neurotrophins differentially regulate voltage-gated ion channels

Neurotrophic factors profoundly affect neuronal differentiation, but whether they influence neuronal phenotype in instructive ways remains unclear: do different neurotrophic factors always trigger identical programs of differentiation or can each impose distinct functional properties even when acting upon the same population of target neurons? We addressed this issue by examining the regulatory effects of the four neurotrophins on the molecular components of electrical excitability, voltage-gated ion channels, within a single cellular context. Using patch clamp methods, we studied neurotrophin regulation of voltage-gated sodium, calcium, and potassium currents in SK-N-SH neuroblastoma cells. We found that each neurotrophin induced a unique pattern of expression of ionic currents despite similar activation of initial signal transduction events. Thus, each neurotrophin imposed a different excitable phenotype even when acting upon the same target cells.     

Multiple learning parameters differentially regulate olfactory generalization.

Sensory representations depend strongly on the descending regulation of perceptual processing. Generalization among similar stimuli is a fundamental cognitive process that defines the extent of the variance in physical stimulus properties that becomes categorized together and associated with a common contingency, thereby establishing units of meaning. The olfactory system provides an experimentally tractable model system in which to study the interactions of these physical and psychological factors within the framework of their underlying neurophysiological mechanisms. The authors here show that olfactory associative learning systematically regulates gradients of odor generalization. Specifically, increasing odor-reward pairings, odor concentration, or reward quality--each a determinant of associative learning--significantly transformed olfactory generalization gradients, each narrowing the range of variance in odor quality perceived as likely to share the learned contingency of a conditioned odor stimulus. However, differences in the qualitative features of these three transformations suggest that these different determinants of learning are not necessarily theoretically interchangeable. These results demonstrate that odor representations are substantially shaped by experience and descending influences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Distinct dendritic cell subsets differentially regulate the class of immune response in vivo

Dendritic cells (DCs) are unique in their ability to stimulate T cells and initiate adaptive immunity. Injection of mice with the cytokine Flt3-ligand (FL) dramatically expands mature lymphoid and myeloid-related DC subsets. In contrast, injection of a polyethylene glycol-modified form of granulocyte/macrophage colony-stimulating factor (GM-CSF) into mice only expands the myeloid-related DC subset. These DC subsets differ in the cytokine profiles they induce in T cells in vivo. The lymphoid-related subset induces high levels of the Th1 cytokines interferon gamma and interleukin (IL)-2 but little or no Th2 cytokines. In contrast, the myeloid-related subset induces large amounts of the Th2 cytokines IL-4 and IL-10, in addition to interferon gamma and IL-2. FL- or GM-CSF-treated mice injected with soluble ovalbumin display dramatic increases in antigen-specific antibody titers, but the isotype profiles seem critically dependent on the cytokine used. Although FL treatment induces up to a 10, 000-fold increase in ovalbumin-specific IgG2a and a more modest increase in IgG1 titers, GM-CSF treatment favors a predominantly IgG1 response with little increase in IgG2a levels. These data suggest that distinct DC subsets have strikingly different influences on the type of immune response generated in vivo and may thus be targets for pharmacological intervention.     

Sex hormones affect spatial abilities during the menstrual cycle.

The aim of this study was (a) to show that different measures of spatial cognition are modulated by the menstrual cycle and (b) to analyze which steroid is responsible for these cognitive alterations. The authors collected blood samples in 3-day intervals over 6 weeks from 12 young women with a regular menstrual cycle to analyze concentrations of estradiol, progesterone, testosterone, luteinizing hormone, and follicle-stimulating hormone. The performance on 3 spatial tests was measured during the menstrual and the midluteal phases. A significant cycle difference in spatial ability as tested by the Mental Rotation Test was found, with high scores during the menstrual phase and low scores during the midluteal phase. Testosterone had a strong and positive influence on mental rotation performance, whereas estradiol had a negative one. These results clearly indicate that testosterone and estradiol are able to modulate spatial cognition during the menstrual cycle. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Progesterone receptor isoforms are differentially regulated by sex steroids in the rat forebrain

We studied the effects of estradiol (E2) and progesterone (P4) on expression of genes coding for PR isoforms in the forebrain of ovariectomized rats by RT-PCR analysis. In the hypothalamus the expression of both PR isoforms was induced by E2 and down-regulated by P4. In the preoptic area these changes were only observed in the PR-B isoform. In contrast, in the hippocampus PR induction by E2 was only observed for PR-A. In this region P4 did not modify the expression of any PR isoform. These results indicate that PR isoforms expression is differentially regulated by sex steroid hormones in distinct forebrain regions and suggest that the tissue-specific regulation of either PR-A or PR-B may be involved in the physiological actions of P4 upon the rat brain.     

Food restriction differentially affects mRNAs encoding the major anterior pituitary tropic hormones

Chronic food restriction (FR) leads to adaptive cellular changes, some of which retard aging. Moreover, some of these changes occur within weeks after onset of FR. Because neuroendocrine mechanisms may mediate these effects, we measured the effect of FR on the messenger ribonucleicacids (mRNAs) encoding all of the tropic hormones of the anterior pituitary (AP). Slot blot and solution hybridization were conducted on AP ribonucleicacid (RNA) samples obtained at 0500 h (AM) and 1500 h (PM) from 3-month-old male Fischer 344 rats fed ad libitum (AL) or FR (60% of AL calories) since 6 weeks of age. PolyA RNA/microgram total RNA was similar in AL and FR rats, indicating that there was no overall effect of FR on mRNA levels. The level of proopiomelanocortin (POMC) mRNA was not reduced by FR when expressed per microgram of RNA or as total AP content. By contrast, the total AP content of the mRNAs encoding LH beta, FSH beta, TSH beta, GH, and PRL was markedly reduced by FR. When expressed per microgram of RNA, however, only GH (AM and PM), FSH beta (AM), TSH beta (PM), and PRL (PM) were reduced by FR. These results reveal that FR differentially affects pituitary tropic hormone mRNA levels within weeks after onset of FR, and are consistent with a role for neuroendocrine alterations in the initiation of adaptive cellular responses to FR.     

Thyroid hormones differentially affect sarcoplasmic reticulum function in rat atria and ventricles

We have recently reported that the short-acting anesthetic and analgesic drug midazolam can produce analgesia and decrease morphine tolerance and dependence in the rat by interacting with the opioid system. This study was designed to investigate the effect of midazolam, morphine, and both together on met-enkephalin levels in the rat. Male Sprague-Dawley rats were divided into four groups: (1) saline-saline; (2) saline-morphine; (3) midazolam-saline, and (4) midazolam-morphine groups. First, a saline or midazolam injection was given intraperitoneally and after 30 min a second injection of saline or morphine was given subcutaneously once daily for 11 days. Animals were sacrificed on the 11th day 60 min after the last injection to measure met-enkephalin by radioimmunoassay. Morphine tolerant animals showed a significant increase in met-enkephalin levels in the cortex (137%) and midbrain (89%), and a significant decrease in met-enkephalin levels in the pituitary (74%), cerebellum (34%) and medulla (72%). Midazolam treated animals showed a significant decrease in met-enkephalin levels in the pituitary (63%), cortex (39%), medulla (58%), kidneys (36%), heart (36%) and adrenals (43%), and a significant increase in met-enkephalin levels in the striatum (54%) and pons (51%). When morphine and midazolam were injected together, midazolam antagonized the increase in met-enkephalin levels in cortex and midbrain region and the decrease in met-enkephalin level in the medulla region observed in morphine tolerant animals. These results indicate that morphine tolerance and dependence is associated with changes in the concentration of met-enkephalin in the brain. Midazolam may inhibit morphine tolerance and dependence by reversing some of the changes induced in met-enkephalin levels in brain by morphine in morphine tolerant and dependent animals.     

MyoD and Myf-5 differentially regulate the development of limb versus trunk skeletal muscle

The myogenic progenitors of epaxial (paraspinal and intercostal) and hypaxial (limb and abdominal wall) musculature are believed to originate in dorsal-medial and ventral-lateral domains, respectively, of the developing somite. To investigate the hypothesis that Myf-5 and MyoD have different roles in the development of epaxial and hypaxial musculature, we further characterized myogenesis in Myf-5- and MyoD-deficient embryos by several approaches. We examined expression of a MyoD-lacZ transgene in Myf-5 and MyoD mutant embryos to characterize the temporal-spatial patterns of myogenesis in mutant embryos. In addition, we performed immunohistochemistry on sectioned Myf-5 and MyoD mutant embryos with antibodies reactive with desmin, nestin, myosin heavy chain, sarcomeric actin, Myf-5, MyoD and myogenin. While MyoD(-/-) embryos displayed normal development of paraspinal and intercostal muscles in the body proper, muscle development in limb buds and brachial arches was delayed by about 2.5 days. By contrast, Myf-5(-/-) embryos displayed normal muscle development in limb buds and brachial arches, and markedly delayed development of paraspinal and intercostal muscles. Although MyoD mutant embryos exhibited delayed development of limb musculature, normal migration of Pax-3-expressing cells into the limb buds and normal subsequent induction of Myf-5 in myogenic precursors was observed. These results suggest that Myf-5 expression in the limb is insufficient for the normal progression of myogenic development. Taken together, these observations strongly support the hypothesis that Myf-5 and MyoD play unique roles in the development of epaxial and hypaxial muscle, respectively.     

Thyroid hormones regulate beta-amyloid gene splicing and protein secretion in neuroblastoma cells

The beta-amyloid protein (Abeta), the major component of the senile plaques found in Alzheimer brains, derives from a larger beta-amyloid precursor protein (APP). Alternative splicing of the APP gene yields three major APP messenger RNAs (mRNAs), which, in turn, give rise to the APP770, APP751, and APP695 protein isoforms. In this study we examined the effects of thyroid hormone on APP expression in N2a-beta neuroblastoma cells. T3 caused a significant increase in the APP770 mRNA band, in detriment of the APP695 mRNA, which was proportionately reduced. In agreement with these results, T3 markedly altered the relative ratio of intracellular APP isoforms, increasing the amount of APP770 and causing an equivalent reduction of the immature APP695 isoform. In accordance with these results, the soluble APP695-derived form was specifically reduced in the culture medium obtained from T3-treated cells. In contrast, the increase in intracellular APP770 was not followed by an enhanced release of soluble derivatives of this isoform. These results suggest that T3 regulates not only APP gene splicing, but also the processing and secretion of the APP peptides. According to our results, thyroid hormone might play a role in the development of Alzheimer's disease by modulating the intracellular and extracellular contents of APP isoforms.     

Sex steroid hormones and genetic susceptibility to breast and prostate cancer

In SPECT, both the noise affecting the data and the discretization of the inverse Radon transform are responsible for the ill-posed nature of the reconstruction. To constrain the problem, we propose a regularized backprojection method (RBP) which takes advantage of the relationships existing between the continuity properties of the projections and those of the reconstructed object. The RBP method involves two stages: first, a statistical model (the fixed-effect model) is used to estimate the noise-free part of the projections. Then, the filtered projections are reconstructed using a backprojection algorithm (spline filtered backprojection) which ensures that the reconstructed object belongs to a space consistent with that containing the projections. The method is illustrated using analytical simulations, and the RBP approach is compared to the conventional filtered backprojection. The effect on the reconstructed slices of the parameters involved in RBP is studied in terms of spatial resolution, homogeneity in uniform regions and quantification. It is shown that appropriate combinations of these parameters yield a better compromise between homogeneity and spatial resolution than conventional FBP, with similar quantification performances.     

Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones

Biopsy specimens of the skin and oral mucosa from twenty-five patients bearing the disseminated form of histoplasmosis (H. capsulatum) associated with AIDS (acquired immunodeficiency syndrome) were studied by histologic and immunohistochemistry techniques. Histologically, the skin lesions showed four different patterns: diffuse macrophage, granulomatous, vasculitic with leukocytoclastic and scarce inflammatory reaction. The cell markers for macrophages, lymphocytes B and T and H. capsulatum revealed CD68, UCHL-1 and L26 associated with variable amounts of fungi.     

Sex differences in anxiety behavior in rats: role of gonadal hormones

These experiments examined the role of gonadal hormones at both the organizational and activational time periods on sex differences in plus-maze behavior. In the first experiment, adult female Long-Evans rats were found to spend more time on the open arms of the plus maze than adult males, indicating less anxious behavior. In the second experiment, male and female subjects received a neonatal treatment (chemical castration with flutamide or tamoxifen, vehicle injection, or no injection) and a prepubertal treatment (gonadectomy, sham surgery, or no surgery). Adult females receiving either neonatal tamoxifen or prepubertal ovariectomy spent less time on the open arms than control females, but females who received both treatments were the most defeminized subjects. Males were not affected by the absence of gonadal hormones at either time period. These experiment indicate that female gonadal hormones play an important role both organizationally and activationally in plus-maze behavior. The role of the GABA receptor complex in mediating this effect is discussed. Knowledge of sex differences in plus-maze behavior may help to make this maze a more useful tool in investigating anxiety behavior in rats.     

Tissue-specific protein kinase C isoforms differentially mediate macrophage TNFalpha and IL-1beta production

Women with vulvar vestibulitis syndrome (VVS) suffer from severe pain and discomfort in the area around the introitus at almost any stimulus that causes pressure within the vestibule. In spite of the severe sensory symptoms present in these women, the influence of the peripheral nerves in the vulvar vestibulum has not been clarified before. In this study the nerve supply in the vestibular mucosa in women with VVS and in healthy women free from vulvar symptoms has been revealed by PGP 9.5 immunohistochemistry. The results show a significant increase in the number of intraepithelial nerve endings in women with VVS, indicating an alteration in the nerve supply in the afflicted area.     

Dopaminergic and glutamatergic blocking drugs differentially regulate glutamic acid decarboxylase mRNA in mouse brain

Dopaminergic and glutamatergic inputs play an important role in regulating the activity of GABAergic neurons in basal ganglia. To understand more fully the biochemical interactions between these neurotransmitter systems, the effects of blocking dopamine and glutamate (N-methyl-D-aspartate) (NMDA) receptors on the expression of glutamic acid decarboxylase (GAD) mRNA were examined. Persistent blockade of dopamine receptors was achieved by daily injections of EEDQ, a relatively non-selective irreversible D1 and D2 dopamine receptor antagonist, or FNM, a relatively selective irreversible D2 dopamine receptor antagonist. Persistent blockade of NMDA receptors was achieved by continuously infusing dizocilpine (MK-801), a non-competitive NMDA receptor antagonist. The levels of GAD mRNA in mouse brain were measured by in situ hybridization histochemistry following treatment with these agents. Repeated administration of EEDQ increased the levels of GAD mRNA in corpus striatum and frontal and parietal cortex; the first significant effects were seen after 4 days of treatment. Treatment with FNM elicited effects similar to those produced by EEDQ, except FNM also significantly increased GAD mRNA in nucleus accumbens. Neither EEDQ nor FNM produced significant effects on GAD mRNA in olfactory tubercle or septum. Infusion of MK-801 produced a rapid and marked decrease in the levels of GAD mRNA in corpus striatum, nucleus accumbens, olfactory tubercle, septum and frontal and parietal cortex; significant changes were seen as early as 2 days of treatment. No significant effects were seen in globus pallidus. Cellular analysis of emulsion autoradiograms from corpus striatum revealed that MK-801 reduced the amount of GAD mRNA in individual cells as well as the proportion of cells expressing high levels of GAD mRNA. These results suggest that dopamine, though its interaction with D2 dopamine receptors, exerts an inhibitory effect on the expression of GAD mRNA, and that glutamate, though its interaction with NMDA receptors, exerts a stimulatory effect on GAD mRNA expression. They show further that the regulation of gene expression by dopamine receptors or NMDA receptors is different in different regions of the brain.