Sex steroid hormones and antibodies to Candida albicans.

The effect of changes in progesterone (P) and estradiol (E2) on titres of antibodies to Candida albicans was studied by measurement of these three parameters in the following endocrinologically diverse human groups: normal females, gonadal dysgenetics, users of a sequential oral contraceptive (Oracon) and normal males. In females, C. albicans titres (mean +/- s.e.m.) were significantly higher (P less than 0.05) in the luteal (74 +/- 14) than in the follicular phase (34 +/- 19) of the cycle, and there were similar significant increases in P and E2. In the gonadal dysgenetic group (n = 29), with E2 levels comparable with males, the antibody titres were also equivalent to those in normal males (40 +/- 0.5), but were significantly lower than those of normal females in the follicular phase (P less than 0.05). In contrast, Oracon users, with high blood progestin levels, had C. albicans titres (118 +/- 15) significantly higher (P less than 0.001) than those of control subjects during the follicular phase. A significant correlation (P less than 0.05) was observed between P and C. albicans titres (mainly IgA) in randomly selected samples (n = 112) from normal females during the follicular and luteal phases, and in two subjects from whom blood samples were drawn daily for the entire cycle. In the latter, an increase in E2 but not P in the late follicular phase was accompanied by a marked decrease in C. albicans titres. No changes were observed in total immunoglobulin levels or antibodies to SRBC or Herpes virus in response to the marked changes in hormones. These results indicate that the production of antibodies to C. albicans may be specifically influenced by sex steroid hormones, being enhanced by P and E2 at low levels but depressed by E2 at high levels.     

Sex steroid hormones and the neural control of breathing

We review evidence that sex steroid hormones including estrogen, progesterone and testosterone are involved in the central neural control of breathing. Sex hormones may exert their effects on respiratory motoneurons via neuromodulators, in particular, the serotonergic system. Recent studies have shown that levels of serotonin (5HT) in the hypoglossal and phrenic nuclei are greater in female than in male rats. Serotonin-dependent plasticity in hypoglossal and phrenic motor output also differs in male and female rats. Changing levels of gonadal hormones throughout the estrus cycle coincide with changing levels of 5HT in respiratory motor nuclei, and gonadectomy in male rats results in a decrease in 5HT-dependent plasticity in respiratory motor output. We speculate that sex steroid hormones are critically involved in adaptations in the neural control of breathing throughout life, and that decreasing levels of these hormones with increasing age may have a negative influence on the respiratory control system in response to challenge.     

Sex and age differences in the impact of the forced swimming test on the levels of steroid hormones

Compared with the adult disorder, depression in children exhibits differences in its neurobiology, particularly in the HPA axis regulation. The bases of such differences can be evaluated in animal models of depression. The objective of the present study was to determine age and sex differences of Wistar rats in the forced swimming test (FST). The influence of sex and age on corticosterone, estrogens and testosterone serum levels was also determined. Prepubertal rats showed immobility, swimming and climbing behaviors during the pre-test and test sessions. In addition, in the prepubertal animals, no sex differences were found during the pre-test and test sessions. Age comparisons indicated no differences in the female groups, however adult males exhibited more immobility and less swimming than young males, in both FST sessions. The young and female rats showed less immobility behavior and increased levels of estrogens after the FST. The present results indicate that the FST is an animal model suitable to evaluate depressive-like behaviors in prepubertal subjects and to explore behavioral changes related to neurodevelopment.     

Sex steroid hormones and adipose tissue metabolism in ovariectomized and adrenalectomized rats

The effects of oestrogen and progesterone, alone or in combination, on regional adipose tissue metabolism and oestrogen binding were examined in rats which were not only ovariectomized but also adrenalectomized to allow a study under conditions such that no endogenous sex steroid production occurred. Under these conditions no effects on food intake of the sex steroid hormones were found. 17-beta-oestradiol plus progesterone tended to increase lipoprotein lipase in the parametrial but not retroperitoneal fat depot, but no effects were found of oestrogen or progesterone alone. Oestradiol alone or in combination with progesterone clearly increased basal and norepinephrine-stimulated lipolysis, most pronounced in the retroperitoneal depot. Progesterone alone had no effect. Cytoplasmic 17-beta-oestradiol binding was highest in the parametrial fat depot in non-substituted rats and decreased dramatically after oestrogen administration. It was concluded that in ovariectomized-adrenalectomized rats, oestrogen alone or in the presence of progesterone facilitates lipolysis, a clear effect which is thus possible to elicit without adrenal hormones. Both sex steroid hormones alone or in combination, have no or weak effects on food intake and lipoprotein lipase activity, respectively. These metabolic events as well as cytoplasmic oestrogen binding show regional variations.     

Pregnancy and sex steroid hormones enhance circulating calcitonin gene-related peptide concentrations in rats

Calcitonin-gene-related peptide (CGRP) is a 37 amino acid neuropeptide synthesized primarily in dorsal root ganglia (DRG) and distributed widely in the perivascular nerves, suggesting that this peptide may play a role in the regulation of peripheral vascular tone. Since female sex steroid hormones have been implicated in the regulation of peripheral vascular tone during pregnancy, we postulated that they may alter the concentration of CGRP in the circulation and thus modulate the increased blood flow observed during pregnancy. In the present study, we measured changes in plasma concentrations of CGRP in non-pregnant, pregnant, and post-partum rats. Groups of ovariectomized rats were treated s.c. for 3 days either with 17beta-oestradiol (2.5 microg per injection twice daily), progesterone (2 mg per injection twice daily), or vehicle. Another group of adult, non-pregnant rats at dioestrus stage of the oestrous cycle was also used in this study. Plasma concentrations of CGRP were higher (P < 0.05) in rats on day 19 of pregnancy (22.0 +/- 3.0 pmol/l) compared to that during delivery (5. 0 +/- 2.0), post-partum day 2 (2.0 +/- 0.7) or in non-pregnant (4.9 +/- 1.6) state. Furthermore, in adult ovariectomized (6.0 +/- 0.6) rats, plasma CGRP concentrations were increased significantly (P < 0. 05) by oestradiol (10.0 +/- 1.0), progesterone (9.5 +/- 1.0) and oestradiol + progesterone (14.0 +/- 1.0). Thus, circulating concentrations of CGRP are elevated during pregnancy and by oestrogen and progesterone, suggesting that the elevated concentrations of CGRP may play an important role in vascular adaptations that occur during pregnancy.     

Sex hormones and sexual behavior.

In certain animals the effects of gonadal steroids on sexual behavior are mediated directly by the central nervous system: however, in humans the degree to which sexual identity or sexual role behavior is directly determined by endocrine function is unclear. Furthermore, the relative importance of hormonal versus psychiatric, social, and cultural factors as determinents of sexual identify is in dispute. The findings of Imperato-McGinley and her associates, published in this issue, tend to support the theory that hormonal factors are of primary importance in determining male sexual identity. Patients with a deficiency of steroid 5alpha-reductase have decreased digydrotestosterone production during fetal development, and are thus born with female-like external genital organs. Generally they are raised as females but during childhood and puberty normal testerone activity takes place; therefore, at puberty the majority of these individuals assume a male identity. This identity change was attributed to androgen activity. Studies of this nature contribute to our understanding of the role of hormones; however, it must be kept in mind that the study provides only circumstantial evidence and that the findings do not rule out the possible influence of psychological, social, or cultural factors on sexual role behavior. For example, male pseudohermaphradites are frequently born with clitoromegaly, and during childhood this may introduce feelings of uncertainty as to sexual identity. Nor is it clear that the change to male identity is the result of the direct effect of testosterone on the central nervous system; the enlargement of accessory male organs at puberty may itself influence sexual role behavior.     

Sex hormones and cardiovascular risk.

Inspection of the age-incidence curve of ischaemic heart disease in both sexes shows an increase in slope for women around the menopause, approaching that of men at older ages. Although the increase is likely to be related to the menopause, epidemiological evidence is not defined. Likewise, there is some suggestion that reproductive factors may be related to the subsequent risk of cardiovascular diseases, since a few studies found an elevated risk in women with an earlier first birth. In terms of prevention and public health considerations, treatments via exogenous hormones are, however, much more important. A systematic overview of the available epidemiological evidence indicates that oestrogen replacement treatment is protective against ischaemic heart disease. The overall relative risks based on 18 studies and greater than 3300 cases was 0.81, with a narrow 95% confidence interval (0.76-0.85), thus suggesting a protective effect of 15-25%. This protection has a plausible biological interpretation in terms of increased high density lipoprotein (HDL) levels. The serum lipoprotein pattern can be unfavourably influenced by progestin supplementation. With reference to oral contraceptives, the relative risk for cardiovascular mortality was increased about twofold in current users. There appears now to be convincing evidence that the elevated risk is restricted to current users.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex steroid hormones in serum and tissue of benign and malignant breast tumor patients

The ability of breast tumors to synthesize sex steroid hormones is well recognized and their local production is thought to play a role in breast cancer development and growth. The aim of this study was to estimate local intra-tumoral and circulating levels of Estrone (E1), Estrone Sulfate (E1S), Estradiol (E2), Estriol (E3), and Testosterone (T) in 33 pre- and postmenopausal women with primary breast cancer in comparison to 12 pre- and postmenopausal women with benign breast tumors. The mean levels of the studied sex hormones were higher in serum and tumor tissue of breast cancer women than those with benign breast tumors apart from Testosterone which showed a significant decrease in pre- and postmenopausal women with breast cancer (P<0.001for follicular phase, P<0.05 for luteal phase, and P<0.005 for postmenopausal). The levels of the five hormones were significantly higher intra-tumoral than in serum of both benign and malignant breast tumor women with E1S as the predominant estrogen. There was only a positive significant correlation between serum and tumor tissue levels of E1 (rs=0.52, P<0.05 for follicular; rs=0.63, P<0.05 for luteal and rs=0.58, P<0.05 for postmenopausal) and a significant correlation between serum and tumor tissue of T (rs=0.64, P<0.05 for follicular; rs=-0.51, P<0.05 for luteal and rs=-0.81, P<0.04 for postmenopausal).     

A detailed investigation of circulating IgE levels in a normal population

Total circulating IgE levels were measured in a carefully selected normal population, using a highly sensitive double antibody assay. The mean level of 36.3 u/ml found in this group is much lower than that reported in all previous studies. No circadian rhythm was evident, but IgE levels varied slightly from day-to-day. IgE levels in 100 serum samples were compared using the double antibody assay and the Phadebas lest kit. based on a solid phase technique. A poor correlation was obtained with values below 100 u/ml, however, there was an excellent correlation for samples with IgE levels above this figure.     

Collagen and steroid hormones

The authors analyse the effects of steroid hormones on collagen, from up to date datas previously published and personal works. Glucocorticoids have catabolic effects; their molecular effects are reviewed. Conversely, oestrogens and androgens have an anabolic effect.     

Viral infections and IgE levels.

Six non-atopic patients with respiratory infections to a variety of viruses demonstrated a consistent drop in IgE levels (35% to 87%) in the convalescent phase compared to the acute phase of infection, suggesting that the viral agent affects T lymphocytes to suppress and hence B lymphocytes to secrete IgE immunoglobulin.     

Mast cells regulate IFN-gamma expression in the skin and circulating IgE levels in allergen-induced skin inflammation.

BACKGROUND: Mast cells are important effector cells in IgE-mediated allergic reactions. They are present in normal skin and increased in skin lesions of patients with atopic dermatitis (AD). OBJECTIVE: We used mice deficient in mast cells (W/W(v)) to assess the role of these cells in a murine model of allergen-induced skin inflammation induced by repeated epicutaneous sensitization with ovalbumin (OVA); the model exhibits many of the characteristics of AD. METHODS: Mice deficient in mast cells were sensitized with OVA. Histologic and immunohistochemical examinations, as well as measurements of IL-4 and IFN-gamma mRNA, were performed on OVA-sensitized skin. Total and antigen-specific serum IgE levels were determined. RESULTS: Infiltration in W/W(v) mice by mononuclear cells, T cells, and eosinophils in OVA-sensitized skin was comparable to that in wild-type (WT) controls. Expression of IL-4 mRNA in sensitized skin sites was similarly increased in WT and W/W(v) mice. However, IFN-gamma mRNA expression was significantly increased in sensitized skin of W/W(v) mice but not in that of WT controls. IL-4 mRNA was readily detectable in unsensitized skin of WT controls but not in that of W/W,(v) mice, whereas expression of IL-12 p40 mRNA was significantly increased in unsensitized skin of W/W(v) mice in comparison with WT controls. Total serum IgE levels were significantly increased after epicutaneous sensitization in W/W(v) mice in comparison with WT controls. CONCLUSION: These results suggest that mast cells regulate IFN-gamma expression in the skin and IgE levels in the circulation in a model of allergen-induced skin inflammation with similarities to AD. This is important, given the role of IFN-gamma in keratinocyte injury in AD and the role of IgE-mediated reactions in exacerbating AD.     

Serum levels of gonadotrophins and steroid hormones in the post-menopause and later life

Changes in the serum levels of gonadotrophins and steroid hormones with increasing age were studied in 449 women aged 40 and over to investigate the relationships between these hormones even very late in life. The levels of oestradiol (E2) and dehydroepiandrosterone sulphate (DHEA-S) fell after age 50 and remained low thereafter. However, while serum oestrone (E1), testosterone (T), delta-4-androstenedione (A) and prolactin (PRL) concentrations also decreased initially after age 50 they subsequently rose again progressively and this increase was in fact significant in the case of E1. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) rose after age 50, but whereas FSH remained elevated, LH decreased late in life. Cortisol (F) increased significantly after age 70. There was a significant correlation between androgens and E1 as well as between E2 and LH, even after age 60. Owing to the great heterogeneity of the population studied, it is not yet possible to speculate as to the physiopathological significance of these observations. It would seem, however, that the negative feedback effect of oestrogens on LH secretion remains operational very late in life.     

Methods of quantifying circulating IgE

Four radioimmunoassay techniques, two conventional and two sandwich, have been used to measure circulating IgE levels in 100 sera. The test sera had IgE levels ranging From 1.0 to 20,000 u/ml, and each was measured at live dilutions, ranging from threefold to 400-fold. The same IgE standards were used throughout, and the optimal range for each assay was determined by assessing data for quality control sera and the WHO standard 69/204. To be of general use in the United Kingdom an IgE test must measure accurately levels as low as 20-30 u IgE/ml. The Phadebas RIST method failed to meet this criterion, and of the remaining tests the double antibody method had the most useful operating range and produced the most reliable results. However, the double antibody method is not available commercially and so, for the majority of laboratories, the Phadebas PRIST technique should be the method chosen.     

IgE levels in nude mice.

IgE levels in nude mice were estimated by the one-step single radial radiodiffusion method antisera prepared by immunization of guinea pigs with an IgE-rich fraction obtained from sera of normal mice infected with Nippostrongylus brasiliensis and immunized with DNP-ovalbumin in alum gel. 3 out of 8 nude mice had IgE levels significantly higher than those of normal mice.     

Sex hormones and behavioral reactions

The paper provides a comparative analysis of the effects of imbalance of gonadal hormones on behavioral processes in rats of both sex. Learning was assesses in active and passive avoidance paradigms, behavior was evaluated in the "open field" test. Hemigonadectomy in male rats or hemiovariectomy in female rats was found to fail to modify the dynamics of acquisition and reproduction of active avoidance and passive reactions as compared to the controls, but to affect the pattern of animal behavior in the "open field" test. Castration of rats of both sex impaired the acquisition and retention of active avoidance performance. Excess of testosterone in male rats significantly inhibited the ability of the animals to form an active avoidance response. Excessive estradiol levels in female rats accelerated the acquisition of active avoidance performance and greatly attenuated extinction of this performance. Gonadal hormonal treatment did not alter the reproducibility of passive avoidance performance. The lack of estrogens resulted in amnesia of passive avoidance performance while that of androgens failed to destroy passive avoidance performance. Excessive estradiol in female rats or its lack in male rats significantly modified the pattern of animal behavior in the "open field" test. The absence of estrogens or their excess did not affect the behavior of rats with exception of individual components.     

Sex hormones and rheumatoid arthritis

Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone as natural immune-suppressors. In male rheumatoid arthritis (RA) patients, androgen replacement seems to ameliorate the disease and supports their involvement in the pathophysiology of the disease. The combination of androgens with cyclosporin A or methotrexate has been found to potentiate the apoptosis of monocytic inflammatory cells as well as to reduce the cell growth at least in vitro. Considerable interest has been devoted in the last years as to whether the use of oral contraceptive pills (OCs) may have a protective effect on the risk of RA. The results of many controlled studies have been found contradictory. At the present time, no consensus has been achieved regarding OCs administration and its relationship to the prevention or development of RA. In addition, an association of estrogen receptor gene polymorphism with age at onset of RA has been observed and might further explain inter-individual clinical and therapeutical-response variations. Local increased estrogen concentrations and decreased androgen levels have been observed in RA synovial fluids and seem to play a more important role in the immune/inflammatory local response.     

Peritoneal fluid volume and levels of steroid hormones and gonadotrophins in peritoneal fluid of normal and norethisterone-treated women.

Peritoneal fluid and blood samples were collected at surgical sterilization from 30 untreated women at various stages of the luteal phase and from 43 women treated with 300 micrograms norethisterone daily. Levels of oestradiol, progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured. The highest peritoneal fluid volume (mean, 23.1 ml) was found in the early luteal phase (LH 0 to + 3) and the lowest (mean, 5.9 ml) in the late luteal phase (LH + 12 to menses). The norethisterone treatment diminished the formation of peritoneal fluid and the degree of inhibition was dependent upon the type of ovarian reaction to norethisterone. Progesterone and oestradiol levels were higher in peritoneal fluid compared to plasma throughout the luteal phase and during norethisterone treatment. A comparison of the levels of these steroids between untreated controls (LH + 8 to + 11) and norethisterone-treated women demonstrated that the progesterone levels in peritoneal fluid were highly reduced by norethisterone treatment, while the oestradiol levels were not affected. The FSH and LH levels were, in contrast to the steroid hormones, significantly lower in peritoneal fluid than in plasma, both in the untreated and the treated women. No differences in the FSH or LH levels between the untreated and treated women were found. The results indicate that the peritoneal fluid volume and the steroid hormone levels in peritoneal fluid vary with the stages of the luteal phase. Norethisterone treatment significantly reduced the peritoneal fluid volume as well as its progesterone concentration, whereas the oestradiol and gonadotrophin levels remained unchanged.