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PubMed1992

Effects of sex hormones on chemotaxis of human peripheral polymorphonuclear leukocytes and monocytes.

The effects of sex hormones on the in vitro chemotaxis of polymorphonuclear leukocytes (PMNs) and monocytes were investigated using fMLP as the chemoattractant. PMNs, monocytes, and plasma were obtained from heparinized peripheral blood of healthy adults. Chemotaxis of PMNs or monocytes treated with sex hormones were tested using 48-well chemotaxis microchambers. The correlation between sex hormone levels in plasma and the chemotactic ability of PMNs from the same donor was also investigated. The chemotaxis of PMNs was enhanced by progesterone, while it was reduced by estradiol. Random migration of PMNs was also enhanced by progesterone and reduced by estradiol. The effect of estradiol on PMN chemotaxis was inhibited by addition of antiestrogens or progesterone. Testosterone did not have a measurable effect on PMN chemotaxis. A significant positive correlation was found between the concentration of progesterone in plasma of females and PMN chemotactic ability in vitro. For males, there was no significant relationship between plasma levels of sex hormones and PMN chemotactic ability. Estradiol and testosterone levels in plasma did not correlate with PMN chemotactic ability. Sex hormones had no effect on the chemotaxis of monocytes. These results suggest that the altered PMN chemotaxis associated with gingival inflammation may be due to the effects of sex hormones.

Adult↗
PubMed1997

Relationship between serum sex hormones and coronary artery disease in postmenopausal women.

Although sex hormones appear to be importantly involved in the development of coronary heart disease, apparently no study has yet reported an alteration in an endogenous sex hormone level in relation to coronary heart disease in women. In an attempt to determine whether any sex hormone abnormality might be a factor in the development of myocardial infarction in women, estradiol and testosterone, as well as sex hormone-binding globulin, insulin, dehydroepiandrosterone sulfate, and risk factors for myocardial infarction, were measured in relation to the degree of coronary artery disease (CAD) in 60 postmenopausal women undergoing coronary angiography. In a multiple-regression analysis with the degree of CAD as the dependent variable and free testosterone (FT), estradiol, age, body mass index, systolic blood pressure, cholesterol, smoking, and insulin as independent variables in the model, only FT (P < .008) and cholesterol (P = .01) were significantly related to the degree of CAD, both positively. To exclude a possible confounding effect due to prior myocardial infarction, the multiple-regression analysis was repeated for the subgroup of 49 patients remaining after excluding the 11 patients who had ever had a myocardial infarction; again only FT (P < .04) and cholesterol (P = .05) were significantly related to the degree of CAD. Neither total testosterone in place of FT nor HDL cholesterol in place of total cholesterol in the model was significantly related to CAD. Sex hormone-binding globulin and dehydroepiandrosterone sulfate, added individually to the model, showed no significant relationship to CAD. These results raise the possibility that in women an elevated FT level may be a risk factor for coronary atherosclerosis.

Aged↗
PubMed2000

Characterisation of the affinity of different anabolics and synthetic hormones to the human androgen receptor, human sex hormone binding globulin and to the bovine progestin receptor.

For the steroidal growth promoters trenbolone acetate (TBA) and melengestrol acetate (MGA) neither the complete spectrum of biological activities nor the potential endocrine disrupting activity of their excreted metabolites in the environment is fully understood. The potency of these substances in [3H]dihydrotestosterone ([3H]-DHT) displacement from the recombinant human androgen receptor (rhAR) and from human sex-hormone binding globulin (hSHBG) was evaluated. In addition, the potency for [3H]-ORG2058 displacement from the bovine uterine progestin receptor (bPR) was tested. For comparison, different anabolics and synthetic hormones were also tested for their binding affinities. For 17beta-trenbolone (17beta-TbOH), the active compound after TBA administration, an affinity the rhAR similar to dihydrotestosterone (DHT) and a slightly higher affinity to the bPR than progesterone were demonstrated. The affinity of the two major metabolites, 17alpha-trenbolone and trendione, was reduced to less than 5% of the 17beta-TbOH-value. The affinity of these three compounds and of MGA to the hSHBG was much lower compared with DHT. MGA showed a 5.3-fold higher affinity than progesterone to the bPR but only a weak affinity to the rhAR. The major MGA metabolites have an affinity to the bPR between 85% and 28% of the affinity of progesterone. In consequence, MGA and TBA metabolites may be hormonally active substances, which will be present in edible tissues and in manure. We conclude that detailed investigations on biodegradation, distribution and bio-efficacy of these substances are necessary.

Anabolic Agents↗
PubMed2002

Analysis of sex-hormone-receptor expression in laryngeal carcinoma.

There are significant differences in how laryngeal cancer affects the two genders, with cases occuring predominantly in males. This has been speculated to result from the different susceptibilities of the tumor cells to steroid sex hormones. Since the sex hormone action is mediated by specific cellular receptors, several previous studies have analyzed the presence of these sex-hormone receptors. However, the data on the receptor status for androgen, estrogen and progesterone receptors in laryngeal carcinomas are controversial. Since some authors have suggested antiandrogen or antiestrogen therapy as an adjuvant treatment for laryngeal carcinoma, we performed a comprehensive study using immunomorphological and biochemical techniques on both in-vivo and in-vitro tumor cells in order to clarify whether major sex-hormone receptors are present or not. We performed an immunohistochemical analysis on 13 patients with laryngeal carcinomas, 8 males and 5 females, using monoclonal antibodies against androgen, estrogen and progesterone receptors. In addition, the presence of estrogen and progesterone receptors was tested biochemically using an enzyme immune assay (EIA). Furthermore, we analyzed immunohistochemically the expression of the hormone receptors in five keratinocyte cell lines originating from laryngeal carcinomas. In all of our tumor samples, as well as in the five tumor cell lines tested, we did not detect any specific immunohistochemical staining for androgen, estrogen and progesterone receptors in the laryngeal carcinoma cells when compared to the positive controls of breast and prostate cancer samples. Similarly, the biochemical analysis did not demonstrate any significant amount of receptor protein in the analyzed cases. In conclusion, the absence of male and female sex-hormone receptors strongly argues against laryngeal carcinomas being sex-hormone-dependent tumors. Therefore, we do not see any rational indication to use a specific antiandrogen or antiestrogen therapy for the adjuvant treatment of laryngeal carcinomas.

Adult↗
PubMed1982

Regulation of brain and hepatic glutathione-S-transferase by sex hormones in rats.

Our results indicate that sex hormones play an important role in the regulation of brain and hepatic GST protein during maturity. The conjugating factor GSH does not appear to be under the influence of sex hormones. These observations are of great significance in view of the possibility of continued exposure to neurotoxic chemicals like DDT and Kepone which can cause significant alterations in levels of sex hormones. A reduced GSH activity could lead to a retarded biotransformation of electrophiles and thus to an enhanced toxicity.

Animals↗
PubMed1984

Sex hormone profiles in oligomenorrheic adolescent girls and the effect of oral contraceptives.

The hormonal profiles and the effect of oral contraceptives (OCs) on 16 oligomenorrheic and 10 regularly menstruating adolescent girls were studied. Testosterone, androstenedione, dehydroepiandrosterone, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex-hormone-binding globulin were determined on blood samples obtained during a control cycle, during OC treatment, and during the follow-up cycle after discontinuation of OC use. The oligomenorrheic girls had significantly higher concentrations of androstenedione and total and free testosterone than regularly menstruating girls during the control cycle. Sex-hormone-binding globulin concentrations were significantly lower in the oligomenorrheic group. Both in oligomenorrheic and regularly menstruating girls OC treatment caused a decrease in the mean concentrations of all hormones, except prolactin, to similar levels. For 2 to 4 weeks after treatment the oligomenorrheic girls had significantly lower levels of androstenedione, total and free testosterone, and luteinizing hormone than before treatment. In the control group there were no significant differences between pretreatment and posttreatment hormone concentrations. The risks and benefits of prescribing OCs for oligomenorrheic adolescent girls are discussed.

Adolescent↗
PubMed2005

Mammalian sex hormones in plants.

The occurrence of mammalian sex hormones and their physiological role in plants is reviewed. These hormones, such as 17beta-estradiol, androsterone, testosterone or progesterone, were present in 60-80% of the plant species investigated. Enzymes responsible for their biosynthesis and conversion were also found in plants. Treatment of the plants with sex hormones or their precursors influenced plant development: cell divisions, root and shoot growth, embryo growth, flowering, pollen tube growth and callus proliferation. The regulatory abilities of mammalian sex hormones in plants makes possible their use in practice, especially in plant in vitro culture.

Animals↗
PubMed1988

Effects of sex hormones on rabbit gallbladder prostaglandin biosynthesis.

The influence of sex hormones on female and male rabbit gallbladder prostaglandin biosynthesis was examined by radiochromatographic analysis of microsomal membrane fractions. Normal male rabbit total cyclooxygenase activity was modest, producing small amounts of PGE2, PGF2 alpha and 6-keto-PGF1 alpha (breakdown product of PGI2). The normal female gallbladder (GB) microsomes demonstrated an increase in total cyclooxygenase activity when compared to the normal male rabbit gallbladder microsomes. The major prostaglandin (PG) products produced were 6-keto-PGF1 alpha, PGE2 (fivefold higher activity than the male), and PGF2 alpha. The effect of exogenous sex hormones was studied by comparing GB PG biosynthesis in male rabbits treated with exogenous estrogen (50 micrograms/kg sub Q X 5 days) and female rabbits treated with exogenous testosterone (2.5 mg/kg sub Q X 5 days). Exogenous estrogen significantly increased total cyclooxygenase activity in the male rabbit GB microsomes with a significant increase in 6-keto-PGF1 alpha production when compared to the normal male. Exogenous testosterone significantly decreased female rabbit GB total cyclooxygenase activity with a significant decrease in PGE2 biosynthesis and a substantial lowering in 6-keto-PGF1 alpha production. These data suggest that the major sex hormones, estrogen and testosterone, have potent but opposite effects on rabbit GB PG biosynthesis. Both sex hormones may contribute to the sex differences found in our original studies in rabbit GB biosynthesis.

Animals↗
PubMed2003

Endogenous sex hormones and cardiovascular disease in men.

Unlike women, men do not experience an abrupt reduction in endogenous sex hormone production. It has, however, become clear that an age-associated decrease in the levels of (bioactive) sex hormones does occur. Whether endogenous sex hormones have an impact on cardiovascular disease has for many years remained largely unknown, but during the last decade more attention has been drawn to the importance of testosterone, estrogens, and adrenal androgens in etiology, prevention, and treatment of male cardiovascular disease. The purpose of this article is to summarize the evidence currently available on the association between endogenous sex hormones and cardiovascular disease in males. Published studies dealing with the relationship between circulating levels of sex hormones and cardiovascular disease in males were reviewed. The studies reviewed in this article suggest that circulating endogenous sex hormones and estrogens have a neutral or beneficial effect on cardiovascular disease in men.

Cardiovascular Diseases↗
PubMed2004

Skin aging and sex hormones in women -- clinical perspectives for intervention by hormone replacement therapy.

The skin, the largest organ of the body, is the organ in which changes associated with aging are most visible. The skin is a target organ for various hormones, and sex steroids have a profound influence on the aging process. A decrease in sex steroids thus induces a reduction of those skin functions that are under hormonal control. Keratinocytes, Langerhans' cells, melanocytes, sebaceous glands, collagen content and the synthesis of hyaluronic acid, for example, are under hormonal influence. Topical application of estrogens has a positive effect on skin aging parameters, whilst numerous studies have also shown the positive influence of systemic hormone replacement therapy on skin aging. As an alternative treatment, phytohormones may be administered, with the structural similarity to 17beta-estradiol explaining their estrogen-like effects. However, isoflavonoids exhibit an inferior biological potency to synthetic estrogens. Although a large number of publications have documented the effects of sex hormones on the aging process, it is obvious that hormone replacement should not be administered as an independent treatment for skin aging.

Estrogen Replacement Therapy↗
PubMed2005

Effects of sex hormones on costimulatory molecule expression in multiple sclerosis.

Sex hormones play a central role as modulators of immune responses and autoimmune diseases. We hypothesized that suppression of MS disease during pregnancy may be mediated by sex steroid hormones via regulation of costimulatory molecules such as CD40L or CD80/CD86 (B7-1/B7-2). We tested two sex hormones that are implicated in immune suppression during pregnancy: estriol and progesterone. We also examined whether this regulation is gender-specific or disease-related. PBMC from untreated relapsing remitting multiple sclerosis (RR MS) patients and controls were examined for expression of T cell and monocyte costimulatory molecules following mitogen stimulation in the presence or absence of sex hormones. In the absence of hormones, we confirmed that mitogen stimulation induced significantly more CD40L on the surface of CD4(+)T cells in MS patients compared to controls, and we extend these findings by showing there were no gender differences in induction of CD40L. Although supra-physiologic doses of hormones mildly suppressed CD40L expression on activated T cells, in vitro exposure to typical pregnancy-related physiologic doses of estriol or progesterone showed very little or no suppression of CD40L. On monocytes, neither estriol nor progesterone significantly altered the expression of CD80/CD86. These results suggest that physiologic doses of estriol or progesterone cannot alter CD40L on T cells or CD80/CD86 on monocytes sufficiently to explain the improvement observed in MS during pregnancy. Thus, although amelioration of MS and other autoimmune diseases during pregnancy is thought to be due to increased sex hormones, the present results do not support a role for suppression of costimulation via estriol or progesterone.

Adult↗
PubMed2006

Usefulness of body mass index as a sufficient adiposity measurement for sex hormone concentration associations in postmenopausal women.

BACKGROUND: Both obesity and sex hormones are known risk factors for postmenopausal breast cancer. Although adiposity and sex hormones have been studied in the past, previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions. In this study, we investigated the usefulness of body mass index (BMI) as a sufficient adiposity measurement to assess associations with sex hormone levels. METHODS: This study was conducted as a cross-sectional analysis within the control segment (0 g alcohol group) of a randomized, crossover design, in which 51 postmenopausal women consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks each as part of a controlled diet. Dual-energy X-ray absorptiometry scans were administered to the women during the control (0 g alcohol) segment, and a blood sample was drawn at the end of that diet period for hormone analysis. RESULTS: In multivariate analysis (adjusted for age, race, family history of breast cancer, parity, and menarche <12 years), women who were overweight or obese had significantly higher serum concentrations of estradiol, bioavailable estradiol, estrone, and estrone sulfate and lower sex hormone-binding globulin than normal weight women (all P < 0.05). In models adjusted for BMI and the covariates above, none of the dual-energy X-ray absorptiometry adiposity measures added further information (all P > 0.10) for these five analytes beyond that of BMI alone. CONCLUSIONS: In this population of postmenopausal women, under carefully controlled dietary conditions, we confirmed previous findings that higher levels of adiposity were associated with higher concentrations of estrogens and lower sex hormone-binding globulin, and we found that the use of the epidemiology-friendly BMI seems sufficient to assess associations with these hormone levels.

Absorptiometry, Photon↗
PubMed1999

Activating effects of cross-sex hormones on cognitive functioning: a study of short-term and long-term hormone effects in transsexuals.

In an earlier study we demonstrated that 3 months of cross-sex hormone treatment clearly influenced cognitive functioning in transsexuals. The aims of the present study were to examine: (a) whether we could replicate these findings in a new group of transsexuals; (b) whether a similar pattern of change could be found for novel tasks, i.e. tasks, not used in the previous study, that measured closely related cognitive abilities; (c) whether the cognitive changes following cross-sex hormone treatment had stabilized after 3 months or continued to develop over a period of 1 year; and finally, (d) whether the effects were quickly reversible when the hormone treatment was temporarily stopped. Again a pronounced effect of androgen treatment was found on spatial ability in female-to-male transsexuals (FMs) over a period of one and a half years. As expected, untreated male-to-female transsexuals (MFs) had higher scores on visuo-spatial tasks than untreated FMs; after 3 months of cross-sex hormone treatment, the group difference had disappeared, while after about 10 months of hormone treatment, the sex difference was reversed. These effects did not disappear after termination of cross-sex hormone therapy for a period of 5 weeks, but continued to change slightly in the same direction. Earlier findings of an opposite effect of cross-sex hormones on verbal fluency (i.e. MFs improved and FMs deteriorated after 3 months of cross-sex hormone treatment) were not replicated in this study, nor did we find an hormonal influence on other cognitive functions. This study shows that testosterone had an enhancing, and not quickly reversible effect, on spatial ability performance, but no deteriorating effect on verbal fluency in adult women (FMs). In contrast, anti-androgen treatment in combination with estrogen therapy had no declining effect on spatial ability, nor an enhancing effect on verbal fluency in adult men (MFs).

Adolescent↗
PubMed1979

Approach to the study of the role of sex hormones in autoimmunity.

Investigators from this laboratory have been studying sex hormones in normal and autoimmune mice for the past 10 years. We have found that immune responses to DNa are influenced by sex hormones. Androgens reduce and estrogens increase both spontaneous and immunization-induced antibodies to single-stranded DNA in NZB X NZW, NZB X C3H, NZB X CBA, NZB X DBA mice. Treatment of female NZB/W mice with testosterone or 5 alpha dihydrotestosterone retards the progress of autoimmunity. Castration is not necessary for this effect. In contrast, danazol has no favorable effect on the disease process. Estrogens cause a marked acceleration of autoimmunity and a reduction in thymus weight. During the course of these studies, we found that a number of problems or variables arise in studying sex hormone effects, including: 1) X-linked genes, 2) metabolism of testosterone to estrogens, 3) dose of hormone, 4) age at which administration is initiated, 5) differential effects of sex hormones on different autoantibodies and various immune responses.

Age Factors↗
PubMed2001

Sex hormones as immunomodulators in health and disease.

In addition to their effects on sexual differentiation and reproduction, sex hormones influence the immune system. This results in a gender dimorphism in the immune function with females having higher immunoglobulin levels and mounting stronger immune responses following immunization or infection than males. The greater immune responsiveness in females is also evident in their increased susceptibility to autoimmune diseases. However, a clear understanding of the myriad of effects that sex hormones have on the immune system is lacking. Studies in normal mice show that estrogen treatment induces polyclonal B cell activation with increased expression of autoantibodies characteristic of autoimmune diseases. Several mechanisms appear to contribute to the break in tolerance and the increase in plasma cell activity including a reduction of the mass of the bone marrow and the thymus, the emergence of sites of extramedullary hematopoiesis and altered susceptibility of B cells to cell death. In addition, sex hormone levels in both humans and experimental models correlated with the activity of their cytokine-secreting cells indicating that sex hormones influence the cytokine milieu and suggesting that altered sex hormonal levels in autoimmune patients contribute to the skewed cytokine milieu characteristic of systemic lupus erythematosus (SLE). While sex hormones alone do not cause autoimmune disease, abnormal hormone levels may provide the stage for other factors (genetic, infectious) to trigger disease. Understanding the physiology of the interaction between sex hormones and immune function and its potential pathological consequences may provide insight into the autoimmune diseases and new directions for their treatment.

Adjuvants, Immunologic↗
PubMed2000

Role of female sex hormones in the development and reversal of dahl hypertension.

Female sex hormones protect against the development of Dahl hypertension mediated by increases in dietary sodium. The role of female sex hormones in the reversal of Dahl hypertension mediated by decreases in dietary sodium is unknown. The goal of this study was to identify sex differences in the reversal of Dahl hypertension and the associated changes in water and electrolyte homeostasis. Male (M, n=8), female (F, n=8), and ovariectomized female (OVX, n=9) Dahl salt-sensitive rats were instrumented with an abdominal radiotelemetry device for 24-hour monitoring of blood pressure (BP) and heart rate. Daily measurements of food intake, water intake, and urine output were recorded as diet was changed from a low-sodium diet (0.15% NaCl) to a diet containing 8% NaCl. The diet was then changed back to 0.15% NaCl. The responses to changes in the salt diet were compared with responses observed in rats (M, n=4; F, n=4; OVX, n=4) that were maintained on 0.15% NaCl during the experiment. Sex differences in BP were observed when M, F, and OVX rats were fed 8% NaCl diet for 2 weeks (152+/-4, 141+/-3, and 154+/-5 mm Hg, respectively). BP was significantly greater (P<0.05) in M and OVX rats than in F rats. Fluid balance (water intake minus urine volume) and sodium balance (sodium intake minus sodium excretion) were similar in all groups on the 8% NaCl diet. BP in time-control M, F, and OVX rats was 121+/-3, 130+/-4, and 162+/-11 mm Hg, respectively. Compared with time-control groups, differences in BP while rats were eating the 8% NaCl diet were observed in M and F rats but not OVX rats. Reinstatement of an NaCl-deficient diet reversed the hypertension in M and F but not OVX rats (124+/-4, 124+/-2, and 145+/-5 mm Hg, respectively). The changes in dietary sodium caused similar changes in renal handling of sodium and water in all groups of rats; therefore, the effect on blood pressure was independent of renal excretory function. The inability to reverse the hypertension by decreasing sodium intake in OVX rats and the development of spontaneous hypertension in OVX females maintained on a low-sodium diet indicates that removal of the female sex hormones predisposes the animal to the development of hypertension that is sodium independent. We conclude that female sex hormones protect Dahl S rats against the development of sodium-dependent and -independent hypertension.

Animals↗
PubMed2003

The gender differences in growth hormone-binding protein and leptin persist in 80-year-old men and women and is not caused by sex hormones.

OBJECTIVE: Leptin and growth hormone-binding protein (GHBP) both show gender differences that might be explained by sex hormones. To study the potential relevance of oestradiol and testosterone, we have examined 80-year-old subjects in whom oestradiol is higher in men than in women. The interrelationships between leptin, insulin, GHBP and fat mass in this age group were also investigated. DESIGN AND SUBJECTS: Ninety-four subjects (55 females and 39 males), all 80 years old, were investigated in a community-based study. None of the investigated subjects was being treated for diabetes mellitus and none of the women had oestrogen replacement. METHODS: Levels of testosterone, oestradiol, SHBG, IGF-I, GHBP, glucose, insulin and leptin were analysed. Body composition was measured with bioimpedance analysis (BIA). RESULTS: As in younger age groups, serum leptin, the ratio leptin/kilogram fat mass and serum GHBP were higher in the women (all, P< or =0.007), although serum oestradiol was higher in the men (P<0.001). There were no significant associations between sex hormones and leptin or GHBP either in women or in men (all, r<0.13, P>0.1). Leptin correlated to kilogram fat mass in both women (r=0.55, P<0.001) and men (r=0.47, P=0.003), but in contrast, there were no significant correlations between GHBP and fat mass and GHBP and IGF-I, either in women or in men (all, r<0.24, P>0.2). Insulin and leptin were significantly associated with GHBP, both in women (r=0.48, P<0.001 and r=0.43, P=0.001, respectively) and in men (r=0.40, P=0.01 and r=0.34, P=0.03, respectively). CONCLUSIONS: Although the 80-year-old men had higher oestradiol levels than the women, the women had higher levels of leptin and GHBP. There were no correlations between sex hormones and leptin and GHBP, which indicates that the gender differences are not caused by sex hormones in old age. In contrast to studies in younger subjects, GHBP did not correlate to fat mass in the investigated 80-year-old men and women. In the older subjects investigated, as in younger subjects, GHBP was significantly correlated with leptin and insulin.

Aged↗
PubMed1983

Relationship of plasma HDL-cholesterol to testosterone, estradiol, and sex-hormone-binding globulin levels in men and women.

The significance of sex hormone levels in determining variation in high-density lipoprotein cholesterol (HDL-C) concentrations was studied in healthy Seventh Day Adventists (vegetarians) and Mormons. These groups were selected to avoid the confounding effects of alcohol consumption and cigarette smoking on HDL-C concentrations. Multivariate analysis showed that testosterone has a strong negative association with HDL-C in men (t = 3.99, P less than 0.001) and women (t = 2.04, P less than 0.05) when controlled for other variables including the concentration of sex-hormone-binding globulin (SHBG). Sex-hormone-binding globulin showed an independent positive association with HDL-C in men (P less than 0.001) and women (P less than 0.001). We postulate that the sex hormones affect HDL-C levels by regulating the activities of two important enzymes involved in the production and catabolism of HDL, namely, lipoprotein lipase and hepatic endothelial lipase. Other factors contributing independently to variation in HDL-C levels in this study were, in men, age and triglyceride, and in women, apoprotein-HDL, triglyceride, systolic blood pressure, heart rate, body mass index, and triceps skinfold thickness. Plasma estradiol concentrations were not significantly associated in either sex.

Adult↗