Active immunization of prepubertal colts against estrogens: hormonal and testicular responses after puberty

Prepubertal Quarter horse colts were immunized at 6 mo of age with either estrone-17-oxime-bovine serum albumin (n = 4; treated) or with albumin only (n = 5; controls). All colts received booster injections of the appropriate antigen at 8, 10, 12, 16 and 20 mo of age. Blood samples were drawn every 20 d from 6 to 26 mo of age; body weights were determined monthly. Immunization against estrone-albumin resulted in increased binding of [3H]-estradiol in serum within 40 d that was maintained through 24 mo of age. Antisera from treated colts crossreacted equally well with estrone and estradiol and moderately with other estrogens; androgens, progesterone and glucocorticoids all cross-reacted less than .005%. Body weights were not affected by treatment. Concentrations of testosterone were generally higher (P less than .05) in estrogen-immunized colts compared with controls after immunization. Concentrations of luteinizing hormone were not affected by treatment, whereas concentrations of follicle-stimulating hormone were initially increased (P less than .05) in treated colts after immunization. At castration at 27 mo of age, estrogen-immunized colts had greater (P less than .05) testicular and parenchymal weights and produced more (P approximately equal to .055) spermatozoa per horse than did control colts. Seminal characteristics immediately before castration were not affected by treatment. It appears that estrogens are involved in the regulation of several reproductive traits in the colt. Moreover, active immunization against estrogen in the prepubertal colt may be a useful method of increasing testicular size and sperm production rates in the stallion after puberty.     

Hormonal systems regulating growth. A reviewDès systèmes hormonaux maîtrisant la croissance. Une revue bibliographiqueWachstumsregulierende hormonsysteme. Eine literaturübersicht

Growth is a complex, highly integrated process. It involves a host of interactions between nutrients, environment, genotype, many very different hormones and the receptors for these hormones in different tissues. The ultimate hormones for growth are the growth hormone-dependent somatomedins. These are purely anabolic agents that stimulate increases in both the number of cells (hyperplasia) and their size (hypertrophy). Although the growth hormone-somatomedins axis is the central route for growth control, many other hormones influence their effectiveness. Growth hormone — despite being essential for somatomedin production — is also lipolytic and diabetogenic. It thus has both anabolic and catabolic actions. Insulin has some direct effects on hypertrophy, but also controls the ability of growth hormone to stimulate somatomedin production by regulating the growth hormone receptors involved in stimulating production of somatomedins. Similarly, thyroid hormones regulate somatomedin receptors. Just as insulin has direct and indirect anabolic actions, so glucocorticoids have catabolic actions of both a direct and indirect nature. Oestrogens also have direct and indirect effects, but these are antagonistic; on the one hand directly stimulating cell growth by hypertrophy and on the other inhibiting somatomedins production.Clearly there has to be a controlling mechanism which allows a change in the hormonal balance towards anabolism for growth to be stimulated. Identifying and altering this factor(s) will be the key to increasing growth by physiological hormonal manipulation. A major candidate for this role of central growth controller is somatostatin, which inhibits the release of growth hormone, insulin and thyroid hormones, and also acts as a regulator connecting nutrient entry and metabolism. Recent experiments which show that immunization against somatostatin increases growth and food conversion efficiency support this hypothesis.     

Protein metabolism in animals treated with anabolic agents

One of the major factors controlling the deposition of protein in an animal is the activity of the hormones circulating in its blood. Many of the anabolic hormones interact with each other e.g. growth hormone and insulin and there is evidence for a direct interaction between catabolic and anabolic hormones e.g. testosterone and glucocorticoids. Exogenously administered hormone-like substances can have marked effects on animal growth. Diethyl stilbestrol acts like an oestrogen elevating plasma insulin and growth hormone concentration. Zeranol probably also acts in a similar way.Trenbolone acetate (TBA) an androgenic agent, is a very effective growth promotor especially in ruminants. Few changes of note in the endogenous plasma hormone concentrations in treated ruminants have been reported although the combined implant of TBA plus 17-oestradiol did depress plasma thyroxine in steers. We have used the rat as a model to test the effects of TBA on protein synthesis and protein degradation rate in the muscle of rats. Protein synthesis and protein degradation in the muscle of treated female rats was shown to be markedly reduced, the increased growth rate being brought about by a greater reduction in the rate of degradation than in the rate of synthesis. Cathepsin D activity in the muscle was also reduced. Attempts to demonstrate a direct action of TBA on muscle have been unsuccessful. The currently favoured hypothesis for the mode of action of TBA is that it interferes with catabolic action of glucocorticoids on muscle protein. This may not be the mode of action of all androgenic agents. Durabolin (nandrolone phenyl propionate) would appear to stimulate both protein synthesis and protein degradation, at least in the rat.     

Environmental modulation of the immune system via the endocrine system

Numerous studies have demonstrated that a variety of hormones have receptors and exert biologic actions on tissues of the immune system. Conversely, cytokines exert biologic actions on the endocrine system. This bidirectional interaction is likely involved in maintenance of physiological and immunologic homeostasis. This paper summarizes a variety of actions of growth hormone (GH), prolactin (PRL), insulin-like growth factor-I (IGF-I), glucocorticoids and thyroid hormones (TH) on the immune system. It then proceeds to put these actions into a hypothetical context whereby these hormones may mediate some changes in immune system function in response to environmental stimuli such as physical and emotional stress, nutritional deprivation and environmental temperature. In the first example, it is proposed that PRL secretion in response to stress may serve an immunomodulatory role in two ways. The first is by stimulating the immune system directly and the second is by dampening or reducing the degree to which glucocorticoids are secreted in response to stress. The second example suggests that the increase in GH secretion and reduced IGF-I secretion in response to protein/energy restriction may have two potential immunomodulatory actions. One action is a direct effect of GH on several components of the immune system. The other is the partitioning of nutrient use away from skeletal muscle growth and toward tissues of higher priority such as the immune system. The third example proposes that the increased secretion of TH during cold environmental temperatures not only increases basic metabolic rate, but also directly stimulates both primary and secondary lymphoid tissues. It is suggested, therefore, that these three hormones are involved in maintaining immune system homeostasis in response to environmental change.     

复方中草药添加剂对荷斯坦奶牛免疫和泌乳性能的影响

试验旨在研究自制的复方中草药添加剂对泌乳奶牛免疫机能与泌乳性能的影响。试验采用4×4拉丁方设计。选择4头胎次、泌乳天数、体重均相近的健康荷斯坦奶牛,分为4组,其中A组为对照组,饲喂基础饲粮,B、C、D组分别在基础饲粮中添加30、50和80 g/d复方中草药。试验分4期进行,每期28 d(预试期7 d,正试期14 d,排空期7 d)。结果显示:1)添加复方中草药显著增加了白细胞数、嗜中性细胞百分比及血小板数(P<0.05);但对血液生化指标无显著影响(P>0.05)。2)添加复方中草药显著降低了丙二醛(MDA)含量(P<0.05);与对照组相比,添加30 g/d复方中草药显著增加了血清免疫球蛋白M(IgM)及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活力(P<0.05)。3)复方中草药添加剂可以增加血清生长激素(GH)和催乳素(PRL)含量,且添加30 g/d时显著增加(P<0.05)。4)与对照组相比,日粮添加30、50和80 g/d可以使产奶量分别增加10.18%、6.79%和5.19%,但是对产奶量、乳成分及体细胞数的影响均不显著(P>0.05)。试验结果表明,复方中草药添加剂可以调节奶牛机体免疫性能和提高抗氧化能力,且每头牛添加30 g/d时效果最佳。但其对奶牛泌乳性能无显著影响。     

Live Brucella abortus rough vaccine strain RB51 stimulates enhanced innate immune response in vitro compared to rough vaccine strain RB51SOD and virulent smooth strain 2308 in murine bone marrow-derived dendritic cells

Brucella spp. are Gram-negative, coccobacillary, facultative intracellular pathogens. B. abortus strain 2308 is a pathogenic strain affecting cattle and humans. Rough B. abortus strain RB51, which lacks the O-side chain of lipopolysaccharide (LPS), is the live attenuated USDA approved vaccine for cattle in the United States. Strain RB51SOD, which overexpresses Cu–Zn superoxide dismutase (SOD), has been shown to confer better protection than strain RB51 in a murine model. Protection against brucellosis is mediated by a strong CD4+ Th₁ and CD8+ Tc₁ adaptive immune response. In order to stimulate a robust adaptive response, a solid innate immune response, including that mediated by dendritic cells, is essential. As dendritic cells (DCs) are highly susceptible to Brucella infection, it is possible that pathogenic strains could limit the innate and thereby adaptive immune response. By contrast, vaccine strains could limit or bolster the innate and subsequent adaptive immune response. Identifying how Brucella vaccines stimulate innate and adaptive immunity is critical for enhancing vaccine efficacy. The ability of rough vaccine strains RB51 and RB51SOD to stimulate DC function has not been characterized. We report that live rough vaccine strain RB51 induced significantly better (p ≤ 0.05) DC maturation and function compared to either strain RB51SOD or smooth virulent strain 2308, based on costimulatory marker expression and cytokine production.     

The release of growth hormone (GH): relation to the thyrotropic- and corticotropic axis in the chicken

In the chicken and other avian species, the secretion of GH is under a dual stimulatory and inhibitory control of hypothalamic hypophysiotropic factors. Additionally, the thyrotropin-releasing hormone (TRH), contrary to the mammalian situation, is also somatotropic and equally important in releasing GH in chick embryos and juvenile chicks compared to the (mammalian) growth hormone-releasing hormone (GHRH) itself. Consequently, the negative feedback loop for GH release not only involves the insulin-like growth factor IGF-I but also thyroid hormones. In adult chickens, TRH does no longer have a clear thyrotropic activity, whereas its somatotropic activity depends on the feeding status of the animal. In addition, as in mammals, the secretion of GH and glucocorticoids is stimulated by ghrelin, a novel peptide predominantly synthesized in the gastrointestinal tract. Two chicken isoforms of the ghrelin receptor have been identified, both of which are highly expressed in the hypothalamus and pituitary, suggesting that a stimulatory effect may be directed at these levels. GH and glucocorticoids control the peripheral thyroid hormone function by down-regulating the hepatic type III deiodinating enzyme (D3) in embryos (GH and glucocorticoids) and in juvenile and adult chickens (GH). Moreover, glucocorticoids help to regulate T3-homeostasis in the brain during embryogenesis by stimulating the type II deiodinase (D2) expression. This way not only a multifactorial release mechanism exists for GH but also a functional entanglement of activities between the somatotropic-, thyrotropic- and corticotropic axis.     

Cross-talk between the immune and endocrine systems

Significant advances have been made in the field of immunophysiology since Selye discovered that acute stressors reduce the size of lymphoid organs. It is known that a variety of hormones other than glucocorticoids affect functional activities of lymphoid cells and macrophages. This paper summarizes recent findings of the effects of glucocorticoids and other hormones on lymphoid cells of domestic animals. Glucocorticoid and beta-adrenergic receptors are up-regulated on activated lymphoid cells. Classic pituitary hormones are synthesized by lymphoid cells, and both growth hormone and prolactin appear to have distinct roles as immunomodulators. In addition, certain activities of lymphoid cells may be behaviorally conditioned. These findings support the hypothesis that changes in the endocrine system affect lymphoid cells. They also suggest that products of the immune system affect the endocrine system. These findings provide a firm functional basis for the possibility of cross-talk between these two physiological systems.     

人参、黄芪（残渣）、五味子（残渣）等对白羽野鸭生产性能和免疫性能的影响

将人参、黄芪（残渣）、五味子（残渣）等中药粉碎后,作为饲料添加剂饲喂白羽野鸭,观察其对白羽野鸭生产性能和免疫性能的影响。结果表明,人参高剂量组、黄芪（残渣）中、高剂量组可促进白羽野鸭的生长;人参高剂量组和中剂量组对免疫器官的生长有促进作用,并且高剂量组还可增加血清总蛋白、白蛋白含量;五味子（残渣）对白羽野鸭的各项指标无显著影响。     

Production of immunoactive inhibin by bovine granulosa cells in serum-free culture: Effects of exogenous steroids and FSH

Granulosa cells from pooled bovine follicles were cultured under chemically-defined (serum-free) conditions to study the effects of exogenous steroids and FSH on production of immunoactive (ia) inhibin, oestradiol and progesterone. Levels of ia-inhibin in media samples and cell lysates were measured by radioimmunoassay (RIA) using an antiserum raised against a synthetic fragment of human inhibin -subunit [hI(1–32)].

Cells secreted measurable amounts of ia-inhibin, oestradiol and progesterone for at least 7 d of culture, although intracellular levels of inhibin were very low, indicating that newly-synthesized ia-inhibin is rapidly released from the cells. Treatment with androstenedione (0.2μmol/l) or testosterone (0.2μmol/l) increased ia-inhibin secretion markedly; levels on Day 5 of culture were approximately 6-fold (P<0.005) higher than control values. In contrast, treatment with the non-aromatizable androgen dihydrotestosterone (DHT; 0.2μmol/l) resulted in only a one- to two-fold increase (P<0.05) over control values (Day 5). Addition of exogenous oestradiol (8nmol/l) markedly increased ia-inhibin secretion (8–9 fold on Day 5; P<0.05) compared with basal levels, whereas progesterone had no effect. Secretion of oestradiol, undetectable in the absence of exogenous androgens, rose daily in the presence of either androstenedione or testosterone, levels rising approximately 6-fold and 9-fold respectively over a 4-d treatment period. Progesterone secretion increased 2-fold over the culture period and was unaffected by any steroid treatment.

Treatment with ovine FSH (10ng/ml) alone stimulated secretion of progesterone over basal levels (3-fold higher on Day 6; P<0.005), but did not affect output of either ia-inhibin or oestradiol. However, exposure to FSH in the presence of androstenedione not only promoted a further 4-fold increase in progesterone output but also led to a dose-dependent suppression of both ia-inhibin (90% lower on Day 6; P<0.001) and oestradiol (80% lower on Day 6; P<0.001) secretion compared to cells treated with androstenedione alone.

These observations indicate that the secretion of ia-inhibin by bovine granulosa cells in culture is positively regulated by oestradiol, implying an autocrine/paracrine role for this hormone in control of ovarian inhibin production. The ability of aromatizable androgens to stimulate secretion of inhibin, coupled with the inability of the non-aromatizable androgen DHT to elicit such an effect, suggests that inhibin output is largely unaffected by androgens prior to their conversion to oestradiol. The absence of any change in output of ia-inhibin or oestradiol following treatment with exogenous progesterone argues against a local role for this steroid hormone in regulation of inhibin or oestradiol production in the bovine follicle. Finally, the observation that co-treatment with FSH and andostenedione not only stimulated progesterone output but also suppressed secretion of ia-inhibin and oestradiol, indicates a synergistic positive effect of FSH and androgens on cellular luteinization.     

The reproductive system at the neuroendocrine-immune interface: focus on LHRH,estrogens and growth factors in LHRH neuron-glial interactions

Bidirectional communication between the neuroendocrine and immune systems plays a pivotal role in health and disease. Signals generated by the hypothalamic-pituitary-gonadal (HPG) axis (i.e. luteinizing hormone-releasing hormone, LHRH, and sex steroids) are major players coordinating the development immune system function. Conversely, products generated by immune system activation exert powerful and longlasting effects on HPG axis activity. In the central nervous system (CNS), one chief neuroendocrine-immune (NEI) compartment is represented by the astroglial cell population and its mediators. Of special interest, the major supporting cells of the brain and the thymus, astrocytes and thymic epithelial cells, share a similar origin and a similar set of peptides, transmitters, hormones and cytokines functioning as paracrine/autocrine regulators. This may explain some fundamental analogies in LHRH regulation of both cell types during ontogeny and in adult life. Hence, the neuropeptide LHRH significantly modulates astrocyte and thymic cell development and function. Here we focus this work on LHRH neuron-glial signaling cascades which dictate major changes during LHRH neuronal differentiation and growth as well as in response to hormonal manipulations and pro-inflammatory challenges. The interplay between LHRH, growth factors, estrogens and pro-inflammatory mediators will be discussed, and the potential physiopathological implications of these findings summarized. The overall study highlights the plasticity of this intersystem cross-talk and emphasize neuron-glial interactions as a key regulatory level of neuroendocrine axes activity.     

On the winter enhancement of adaptive humoral immunity: hypothesis testing in desert hamsters (Phodopus roborovskii: Cricetidae,Rodentia) kept under long‐day and short‐day photoperiod

We tested the winter immunity enhancement hypothesis (WIEH) on male desert hamsters (Phodopus roborovskii) kept under long‐day (LD) and short‐day (SD) photoperiods. We assumed that under SD in a laboratory, the adaptive humoral immune responsiveness to the antigenic challenge would be enhanced due to the lack of winter physical stressors and food shortages and/or because of the action of an endogenous winter bolstering mechanism, while under LD the immune responsiveness would be suppressed by the activity of the reproductive system. The results support the WIEH in part. We did not find a difference in antibody production in response to sheep erythrocytes between SD and LD hamsters, but SD males had the lower number of granulocytes and the higher number of lymphocytes in white blood cell counts. Reproductive activity was lower in SD males. These males demonstrated an increase in their mass‐specific resting metabolic rate, their mass‐specific maximal metabolic rate and their level of cortisol. The result of a generalized linear model analysis indicates the negative effect on secondary immunoresponsiveness to sheep erythrocytes of mid‐ventral gland size, the organ characterizing individual reproductive quality, and designates a tradeoff between antibody production and reproductive effort. The mass‐independent maximal metabolic rate also negatively affected antibody production, indicating a tradeoff between maximal aerobic performance and the adaptive immune function. The higher stress in SD males seems to be the most likely reason for the lack of the effect of daylight duration on antibody production.     

Central role of insulin in growth and development

Insulin has been shown to have an impact on both prenatal and postnatal growth. Specific mechanisms of insulin action on adipose cell function and lipid storage are well defined. Insulin probably acts in concert with other anabolic factors (i.e., growth hormone and somatomedins) to stimulate muscle protein anabolism and suppress protein catabolism (Figure 2). Insulin also plays a role in energy balance regulation by the hypothalamus, however exact mechanisms of effects on brain metabolism have not been clearly identified.     

Non-genomic actions of progesterone and estrogens in regulating reproductive events in domestic animals

It has been established that nuclear receptors mediate the action of estrogens and progestins in regulating gene expression in the hypothalamic-hypophyseal-gonadal axis of domestic animals during various reproductive states. Results of recent in vitro studies suggest that estradiol-17beta and progesterone can act non-genomically to affect signal transduction responses in target cells by binding to receptors in the plasma membrane. The genomic action of steroids is generally detectable in hours to days whereas non-genomic responses of cells occur in seconds to minutes. The nature of the plasma membrane receptors for estrogens and progesterone has been explored but has not been conclusively established for all cell types studied. In the ewe, estradiol-17beta or estradiol-bovine serum albumin conjugate has been shown by in vitro and in vivo approaches to act non-genomically to suppress luteinizing hormone secretion by gonadotropes and stimulate production of nitric oxide by uterine arterial endothelial cells. Progesterone has been shown to inhibit oxytocin (OT) binding to its receptor in isolated ovine endometrial plasma membranes. This non-genomic action of progesterone blocks OT activation of the phosphoinositide cascade and production of prostaglandin F(2alpha) by ovine and bovine endometrium. The acrosome reaction of caprine and porcine spermatozoa is activated by the non-genomic action of progesterone. Further research is required to define the biological significances of the non-genomic actions of estrogens and progestins.     

Regulation of pituitary somatotroph differentiation by hormones of peripheral endocrine glands

Anterior pituitary somatotroph differentiation occurs during chick embryonic and rat fetal development. A number of findings support the hypothesis that differentiation of these growth hormone (GH) producing cells in the chick and the rat is regulated by adrenal glucocorticoids and thyroid hormones. Somatotroph differentiation can be induced in cultures of chick embryonic and rat fetal pituitary cells with adrenal glucocorticoids and this effect can be modulated by concomitant treatment with thyroid hormones. Plasma levels of thyroid hormones, corticosterone and adrenocorticotropic hormone increase during development, consistent with the ontogeny of somatotrophs. Treatment of chick embryos or rat fetuses with glucocorticoids in vivo induces premature somatotroph differentiation, indicating that the adrenal gland, and ultimately anterior pituitary corticotrophs, may function to regulate pituitary GH cell differentiation during development. Administration of thyroid hormones in vivo also increases somatotrophs prematurely, and administration of the thyroid hormone synthesis inhibitor methimazole inhibits somatotroph differentiation in vivo, suggesting that endogenous thyroid hormone synthesis contributes to normal somatotroph differentiation. Our working model for the regulation of somatotroph differentiation during normal development includes modulation by elements of the hypothalamo-pituitary-adrenal and hypothalamo-pituitary-thyroid axes. Additional research is reviewed defining the mechanism of action for these peripheral hormones in induction of pituitary GH gene expression during development.     

The control of adenohypophysial hormone secretion by amino acids and peptides in swine

Several different amino acids and peptides control secretion of adenohypophysial hormones and this control may be indirect, via the modulation of hypothalamic hormone secretion. Indeed, classical hypothalamic hormones (e.g., gonadotropin-releasing hormone [GnRH], growth hormone-releasing hormone [GHRH], somatostatin, etc.) may be released into the hypothalamo-hypophysial portal vasculature, travel to the adenohypophysis and there stimulate or inhibit secretion of hormones. Alternatively, some amino acids and peptides exert direct stimulatory or inhibitory effects on the adenohypophysis, thereby impacting hormone secretion. In swine, the most extensively studied modulators of adenohypophysial hormone secretion are the excitatory amino acids (ExAA), namely glutamate and aspartate, and the endogenous opioid peptides (EOP). In general, excitatory amino acids stimulate release of luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), and prolactin (PRL). Secretion of adenohypophysial hormones induced by ExAA is primarily, but perhaps not exclusively, a consequence of action at the central nervous system. By acting primarily at the level of the central nervous system, EOP inhibit LH secretion, stimulate GH release and depending on the animal model studied, exert either stimulatory or inhibitory influences on PRL secretion. However, the EOP also inhibited LH release by direct action on the adenohypophysis. More recently, peptides such as neuropeptide-Y (NPY), orexin-B, ghrelin, galanin, and substance P have been evaluated for possible roles in controlling adenohypophysial hormone secretion in swine. For example, NPY, orexin-B, and ghrelin increased basal GH secretion and modulated the GH response to GHRH, at least in part, by direct action on the adenohypophysis. Secretion of LH was stimulated by orexin-B, galanin, and substance P from porcine pituitary cells in vitro. Because the ExAA and various peptides modulate secretion of adenohypophysial hormones, these compounds may play an important role in regulating swine growth and reproduction.     

β-葡聚糖的免疫增强作用机理研究进展

β-葡聚糖具有免疫调节、抗肿瘤、抗感染等多种生物活性和功能。β-葡聚糖作为非特异性的免疫调节剂，不仅能激活免疫细胞，还能促进细胞因子生成，激活补体系统，促进抗体产生，对免疫系统发挥多方面的调节作用。作者将对β-葡聚糖免疫增强的分子机理的研究进展作一概述。近年来从分子水平研究结果表明，多糖通过与巨噬细胞和嗜中性粒细胞、淋巴细胞表面多糖受体相结合，影响细胞的信息传递过程，从而影响这类细胞基因表达和淋巴细胞功能，调节机体免疫功能，淋巴细胞的多种功能均与细胞内cAMP和cGMP的含量及其比值变化有关。研究结果显示，β-葡聚糖具有调节细胞内cAMP和cGMP水平的功能。 另外，β-葡聚糖对免疫细胞NO生成具有明显的促进作用，并与干扰素具有协同促进作用，多糖可影响淋巴细胞前列腺素的分泌，调节免疫功能。阐明多糖的免疫学机理有助于开发新型免疫增强制剂。     

Effect of dietary addition of seaweed and licorice on the immune performance of pigs

In pig production, dietary additive antibiotics are usually used for growth stimulation and disease prevention, although there is public concern about the increased incidence of resistant antibiotics and food safety. It is possible that such antibiotics might be replaced by naturally derived products such as seaweed and licorice. In this study, we evaluated the effect of dietary addition of seaweed and licorice on enhancing the immune function in swine. The animals of each group (eight animals per group) were sensitized at day 42 and 49, and the immunoglobulin production and the expression of cytokines were detected by the ELISA and real‐time PCR. As the results, saliva IgA production of the seaweed‐treated group increased around five times compared to that of control (day 56). Delayed hypersensitivity reaction and IgG production of the seaweed‐treated group increased around 1.8–2.0 times. In addition, enhanced saliva IgA production was detected at day 50 (around two times) and day 51 (around five times) by the licorice treatment, and lower expression level of tumor necrosis factor‐α messenger RNA at day 51 (around 1/25) was observed in the licorice treatment. We conclude that the replacement of antibiotics by naturally derived dietary additives might be feasible for immune system enhancement.     

Expression of genes related to corticotropin production and glucocorticoid feedback in corticotroph adenomas of dogs with Cushing's disease

Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to negative feedback by glucocorticoids. In this study, we examined gene expression related to adrenocorticotropic hormone (ACTH) production and secretion, and the negative feedback by glucocorticoids in canine corticotroph adenoma. We used resected corticotroph adenomas from 10 dogs with Cushing's disease. In order to investigate the alteration of gene expression between corticotroph adenoma and normal corticotrophic cells, ACTH-positive cells in the anterior lobe were microdissected using a laser-capture microdissection system, and mRNA levels of proopiomelanocortin (POMC), corticotropin releasing hormone receptor 1 (CRHR1), glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and 11 beta hydroxysteroid dehydrogenase (11HSD) type 1 and type 2 were determined using real-time RT-PCR. POMC, CRHR1, and 11HSD2 mRNA levels in corticotroph adenoma were greater than those in normal corticotrophic cells (POMC, 5.5-fold; CRHR1, 4.9-fold; 11HSD2, 4.2-fold, P<0.01, respectively). MR and 11HSD1 mRNA levels in corticotroph adenoma were lower than those in normal corticotrophic cells (MR, 2.2-fold; 11HSD1, 2.9-fold, P<0.01, respectively). GR mRNA levels did not differ between corticotroph adenoma and normal corticotrophic cells. Our results may help to understand the increased ACTH production and the resistance to negative feedback suppression by glucocorticoids in canine corticotroph adenomas. These changes in gene expression may have a role in the growth of canine corticotroph adenoma, and help elucidate the pathophysiology of dogs with Cushing's disease.     

Differential effects of experimental hyperthyroidism on declined immunity of broiler chicken

Thyroid hormones (THs) are involved in the development of lymphoid organs and regulation of immune function in birds. However, their role as an immune‐modulator in the hyperthyroid state is still debatable. To explore the interrelationship of thyroxine (T₄) and the immune system, chicks were divided into three groups. Group I was comprised of control birds, who received the basal diet while group II and III were given diets supplemented with 5 μg and 10 μg thyroxine/kg feed, respectively, from 15 to 28 days of age. Cell‐mediated immune response was evaluated through in vitro abdominal macrophage phagocytosis assay, macrophage nitric oxide (NO) production, heterophil‐to‐lymphocyte (H:L) ratio and delayed‐type hypersensitivity response against phytohemagglutinin (PHA). Humoural immune response was assessed through serum IgG and IgM antibody production against sheep red blood cells (SRBCs) and antibody production against infectious bronchitis virus (IBV). Sampling was carried out at 7, 14 and 21 days of treatment. Results have shown higher levels (p < .001) of circulating T₄ in both treatment groups compared to the control group. There was a lower (p < .05) macrophage engulfment percentage, an increase in H:L ratio (p < .001) in treated birds, while their NO production remained higher (p < .05) in thyroxine supplemented groups after bacterial lipopolysaccharide stimulation. The humoural immune response revealed a significant decline (p < .001) in IgG, IgM antibody production against SRBCs but IBV circulating antibodies increased with age. In conclusion, hyperthyroidism has a strong co‐relation with decreased immune performance of birds.