Nancy Olsen | De Anza College (original) (raw)

Papers by Nancy Olsen

American Indian Quarterly, 1987

Mechanisms of androgen-induced thymic involution are largely undefined. We have found that signif... more Mechanisms of androgen-induced thymic involution are largely undefined. We have found that significant decreases in thymic size occur 2-4 h after a dose of testosterone is administered to castrated male mice. This rapid rate of change suggests a role for androgeninduced apoptosis in modulating the size and composition of the thymus. Using thymic organ cultures to define these effects of androgens, we found that dihydrotestosterone treatment of thymus tissues from females or from castrated males results in enhancement of thymocyte apoptosis. Intact (androgen-replete) or testicular feminization, Tfm/Y (androgen-resistant) mice failed to show apoptotic change with androgen treatment, although the apoptotic response to glucocorticoids was present, suggesting a requirement for a functional androgen receptor. Acceleration of thymocyte apoptosis by androgens may mediate processes of thymocyte selection, with the potential to impart gender-specific characteristics on the peripheral T cell repertoire.

The American Journal of the Medical Sciences, 1995

ABSTRACT

Immunology, Feb 1, 1995

While it is generally recognized that females show enhanced cell-mediated and antibody responses ... more While it is generally recognized that females show enhanced cell-mediated and antibody responses to antigenic stimulation, the physiological basis for this observed sexual dimorphism of the immune response is not well understood. We report here studies on the effects of androgen deficiency on the peripheral immune system. Intact male mice were compared to animals castrated 3-4 months previously. Phenotypic characterization of thymocyte and lymphocyte subpopulations was carried out using dual-colour flow cytometry. In vitro production by spleen cells of interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma), and levels of total immunoglobulin and autoreactive antibodies was measured by specific immunoassays. In addition to thymic hypertrophy, castrated animals showed significant splenic enlargement, which was largely owing to expansion of the B-cell population. The castrated spleens contained relatively fewer mature T cells than intact controls (P < or = 0.001), but culture supernatants from these spleen cells contained higher levels of IL-2 and IFN-gamma than control cultures (P < 0.04). Levels of in vitro antibody synthesis (IgM, IgG, IgA) were not higher in castrated animals compared to controls, but the castrate spleen cell cultures showed increased levels of production of two autoreactive antibodies, anti-IgG (rheumatoid factor) and anti-thyroglobulin. These data suggest that androgen deprivation results in a relative decrease in the number of mature peripheral T cells, but those which reach the spleen have functional characteristics suggestive of enhanced activation. Dysregulation in the B-cell compartment may be the result of altered effects of T-cell-mediated control.

Immunology, May 1, 1991

The presence of androgen receptors in thymocytes and the well-described effects of exogenous andr... more The presence of androgen receptors in thymocytes and the well-described effects of exogenous androgens on thymus size suggest a role for androgenic hormones in thymocyte growth and maturation. Testicular feminization (Tfm/Y) mice which bear a heritable defect in the androgen receptor protein were studied to investigate how androgens might influence immune phenotype and function. These mice were compared to two types ofcontrols; their Tabby/Y normal male littermates and male mice of the C57 B1/6 strain from which the Tabby and Tfm mice were derived. Thymuses and spleens from Tfm/Y mice were larger than both types of controls. Phenotypic differences in thymocyte and splenocyte subpopulations identified by the T-cell markers CD3, CD4 and CD8 suggested that T-cell maturation was altered in the androgen-resistant animal. However, both Ta/Y and Tfm/Y were found to be high producers of interleukin-4 (IL-4) by both spleen and thymus cells, while cells from the C57 mice produced predominantly IL-2. These findings suggest that some immunological features of the Tfm/Y mouse may be related to its defect in androgen action, but that high levels of IL-4 production are probably related to other genetic changes in the C57 background.

Experimental Parasitology, Sep 30, 1992

In parallel studies of Schistosoma mansoni infections in male and female CBA/J mice, major sex-re... more In parallel studies of Schistosoma mansoni infections in male and female CBA/J mice, major sex-related differences are seen in the development of infection and disease. Upon equal subcutaneous exposures to 45 cercariae female mice present a more severe clinical course with consequent higher mortality than male mice. By 12 weeks of infection, more than 80% of female mice die, while less than 20% of infected males succumb to infection. This greater index of mortality is apparently due to the higher susceptibility of female mice to the development of adult worms. Exposed to 45 cercariae, virtually all females develop patent infections, but 8-34% of male mice do not do so. Also, the recovery rate of adult worms per cercariae from female mice is much higher than that from males, indicating that schistosomula are more successful in developing into adult worms in female mice. Additional studies indicate that this dichotomy of schistosomiasis in the sexes is not restricted to mice of the CBA/J strain, but also occurs in C57BL/6 and outbred CF1 strain mice.

The American Journal of the Medical Sciences, Oct 1, 1995

Systemic lupus erythematosus occurs with much greater frequency in females than in males, and in ... more Systemic lupus erythematosus occurs with much greater frequency in females than in males, and in some reports, researchers suggested that treatment with androgenic hormones might have therapeutic effects in this disease. The authors report a case of systemic lupus erythematosus in a hypogonadal male with Klinefelter's syndrome who was treated with testosterone in doses sufficient to normalize the serum level of this hormone to the adult male range. Hematologic and serologic abnormalities, including elevated levels of anti-DNA antibodies and depressed complement levels, returned to normal within 9 months of increasing the testosterone dose. The findings in this patient indicate that androgenic steroids can exert significant effects on immune parameters, and suggest that effects of androgens on the immune system may contribute to the sexual dimorphism of autoimmune disease.

Endocrinology, Apr 1, 2001

Castration of normal male rodents results in significant enlargement of the thymus, and androgen ... more Castration of normal male rodents results in significant enlargement of the thymus, and androgen replacement reverses these changes. Androgen-resistant testicular feminization (Tfm) mice also show significant thymus enlargement, which suggests that these changes are mediated by the androgen receptor (AR). The cellular targets of androgen action in the thymus are not known, but may include the lymphoid cells (thymocytes) as well as nonlymphoid epithelial cells, both of which have been believed to express AR. In the present study immunohistochemical analysis and hormone binding assays were used to demonstrate the presence of AR in thymic epithelial cells. The physiological significance of this epithelial cell AR expression was defined by further studies performed in vivo using

The Journal of Gender Specific Medicine Jgsm the Official Journal of the Partnership For Women S Health at Columbia, 2002

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that, like most autoimmune diseases, i... more Rheumatoid arthritis (RA) is a chronic autoimmune disorder that, like most autoimmune diseases, is more common in women than in men. A significant body of evidence implicates gender-specific factors in facilitating the development of RA. Pregnancy has an ameliorating effect on disease activity, while the disease tends to flare in the postpartum period. Estrogen-containing oral contraceptives can modify the disease course or onset, hinting at a role for this hormone in disease pathogenesis. Breast-feeding appears to increase the risk of RA, possibly through the actions of the lactation hormone prolactin. Nonhormonal factors associated with pregnancy may also be important in women with RA, especially the degree of maternal-fetal human leukocyte antigen (HLA) incompatibility. This article reviews data from human clinical and epidemiologic investigations as well as experimental findings in animal models of chronic arthritis. Possible mechanisms by which gender-specific factors modulate immune function are also discussed.

Androgens and Androgen Receptor, 2002

12 ANDROGENS IN IMMUNOLOGY AND AUTOIMMUNE DISEASES Nancy J. Olsen and William J. Kovacs Vanderbil... more 12 ANDROGENS IN IMMUNOLOGY AND AUTOIMMUNE DISEASES Nancy J. Olsen and William J. Kovacs Vanderbilt University School of Medicine and ... This has been referred to as the " immunocompetence handicap" hypothesis (Folstad and Karter, 1992; Eens et al., 2000). ...

Autoimmune Endocrinopathies, 1999

Endocrine connections, 2014

Clinical and experimental evidence support a role for gonadal steroids in modulating the expressi... more Clinical and experimental evidence support a role for gonadal steroids in modulating the expression and course of autoimmune diseases such as lupus. Whether or not inherited variation in sensitivity to circulating androgenic hormones could influence the manifestations of such disease is, however, unknown. We sought to determine whether differences in androgen sensitivity conferred by variation in the exon 1 CAG repeat region of the androgen receptor (AR) gene were associated with differences in the clinical or humoral immune manifestations of lupus in a cohort of female subjects. We found that shorter AR CAG repeat lengths in lupus subjects correlated with a higher Systemic Lupus Erythematosus Disease Activity Index score, higher ANA levels, and expression of a broader array of IgG autoantibodies. Our findings of more severe clinical manifestations and more exuberant humoral autoimmunity in women with a shorter AR exon 1 CAG repeat length suggest a role for genetically determined se...

Journal of investigative medicine : the official publication of the American Federation for Clinical Research, 2011

The thymus has long been recognized as a target for the actions of androgenic hormones, but it ha... more The thymus has long been recognized as a target for the actions of androgenic hormones, but it has only been recently recognized that alterations in circulating levels of gonadal steroids might affect thymic output of T cells. We had the opportunity to examine parameters of thymic cellular output in several hypogonadal men undergoing androgen replacement therapy. Circulating naive (CD4+CD45RA+) T cells were quantitated by flow cytometric analysis of peripheral blood mononuclear cells. Cells bearing T-cell receptor excision circles were quantitated using real-time polymerase chain reaction amplification of DNA isolated from peripheral blood mononuclear cells from healthy men and from hypogonadal men before and after testosterone replacement therapy. CD4+CD45+ (naive) T cells comprised 10.5% of lymphocytes in healthy males; this proportion was greatly increased in 2 hypogonadal men (35.5% and 44.4%). One man was studied sequentially during treatment with physiologic doses of testoster...

Immunology, 1995

Nature Reviews Rheumatology, 2011

Women are more likely than men to develop rheumatoid arthritis (RA), and recent data suggest that... more Women are more likely than men to develop rheumatoid arthritis (RA), and recent data suggest that they also suffer greater disability than men with this disease. The reasons for these sexually dimorphic patterns of disease incidence and progression are unknown, but investigations into the underlying mechanisms could provide useful insights into RA pathogenesis and may also suggest new treatment approaches. The processes of sexual differentiation involve genetic input, gonadal hormone signaling and responses from target cells and tissues. Layered upon these processes are behavioral characteristics of males and females acquired as a result of their social context. Differences in disease presentation between the sexes could be the result of complex combinations of all these factors. Recent research suggests that the developmental processes of sexual differentiation might render women more susceptible than men to similar levels of immune or inflammatory burden by virtue of sex-specific differences in body composition and structure.