Effect of Female Sex Hormones on the Immune Response against Chlamydia abortus and on Protection Conferred by an Inactivated Experimental Vaccine in a Mouse Model

Mice are valuable models extensively used to test vaccine candidates against Chlamydia abortus and to clarify immunopathological mechanisms of the bacteria. As this pathogen has the ability to reactivate during pregnancy, it is important to deepen the knowledge and understanding of some of the effects of female hormones on immunity and vaccination. This study is aimed at describing the role of sex hormones in the pathology of OEA during chlamydial clearance using ovariectomised mice and also gaining an understanding of how 17β-oestradiol or progesterone may impact the effectiveness of vaccination. Animals were treated with sex hormones and infected with C. abortus, and the kinetics of infection and immune response were analysed by means of bacterial isolation, histopathology, and immunohistochemistry. In a second phase of the study, protection conferred by an experimental vaccine after hormone treatment was assessed. Oestradiol showed a stimulatory effect on the immune response during infection, with a more efficient recruitment of macrophages and T-cells at the infection site. Furthermore, after vaccination, oestradiol-treated animals showed a stronger protection against infection, indicating that this hormone has a positive effect, stimulating a specific memory response to the pathogen.

Role of sex hormones in modulating myocardial perfusion and coronary flow reserve

Background A growing body of evidence highlights sex differences in the diagnostic accuracy of cardiovascular imaging modalities. Nonetheless, the role of sex hormones in modulating myocardial perfusion and coronary flow reserve (CFR) is currently unclear. The aim of our study was to assess the impact of female and male sex hormones on myocardial perfusion and CFR. Methods Rest and stress myocardial perfusion imaging (MPI) was conducted by small animal positron emission tomography (PET) with [18F]flurpiridaz in a total of 56 mice (7–8 months old) including gonadectomized (Gx) and sham-operated males and females, respectively. Myocardial [18F]flurpiridaz uptake (% injected dose per mL, % ID/mL) was used as a surrogate for myocardial perfusion at rest and following intravenous regadenoson injection, as previously reported. Apparent coronary flow reserve (CFRApp) was calculated as the ratio of stress and rest myocardial perfusion. Left ventricular (LV) morphology and function were assessed by cardiac magnetic resonance (CMR) imaging. Results Orchiectomy resulted in a significant decrease of resting myocardial perfusion (Gx vs. sham, 19.4 ± 1.0 vs. 22.2 ± 0.7 % ID/mL, p = 0.034), while myocardial perfusion at stress remained unchanged (Gx vs. sham, 27.5 ± 1.2 vs. 27.3 ± 1.2 % ID/mL, p = 0.896). Accordingly, CFRApp was substantially higher in orchiectomized males (Gx vs. sham, 1.43 ± 0.04 vs. 1.23 ± 0.05, p = 0.004), and low serum testosterone levels were linked to a blunted resting myocardial perfusion (r = 0.438, p = 0.020) as well as an enhanced CFRApp (r = −0.500, p = 0.007). In contrast, oophorectomy did not affect myocardial perfusion in females. Of note, orchiectomized males showed a reduced LV mass, stroke volume, and left ventricular ejection fraction (LVEF) on CMR, while no such effects were observed in oophorectomized females. Conclusion Our experimental data in mice indicate that sex differences in myocardial perfusion are primarily driven by testosterone. Given the diagnostic importance of PET-MPI in clinical routine, further studies are warranted to determine whether testosterone levels affect the interpretation of myocardial perfusion findings in patients.

Unexplored functions of sex hormones in glioblastoma cancer stem cells

Biological sex impacts a wide array of molecular and cellular functions that impact organismal development and can influence disease trajectory in a variety of pathophysiological states. In non-reproductive cancers, epidemiological sex differences have been observed in a series of tumors, and recent work has identified previously unappreciated sex differences in molecular genetics and immune response. However, the extent of these sex differences in terms of drivers of tumor growth and therapeutic response is less clear. In glioblastoma, the most common primary malignant brain tumor, there is a male bias in incidence and outcome, and key genetic and epigenetic differences, as well as differences in immune response driven by immune-suppressive myeloid populations, have recently been revealed. Glioblastoma is a prototypic tumor in which cellular heterogeneity is driven by populations of therapeutically resistant cancer stem cells (CSCs) that underlie tumor growth and recurrence. There is emerging evidence that GBM CSCs may show a sex difference, with male tumor cells showing enhanced self-renewal, but how sex differences impact CSC function is not clear. In this mini-review, we focus on how sex hormones may impact CSCs in GBM and implications for other cancers with a pronounced CSC population. We also explore opportunities to leverage new models to better understand the contribution of sex hormones versus sex chromosomes to CSC function. With the rising interest in sex differences in cancer, there is an immediate need to understand the extent to which sex differences impact tumor growth, including effects on CSC function.

Effect of a bradykinin potentiating factor separated from honey bee venom on thyroid gland and testis in hypothyroid white rats

Background Animal venoms have been known as a source of drugs beneficial to human health. Accordingly, this study was designed to determine the effect of bradykinin potentiating factor (BPF) separated from honey bee venom, Apis mellifera on histological structure, thyroid and male sex hormones of the thyroid gland and testis in a model of hypothyroid male white rats induced by carbimazole. Results This study includes male rats divided into 6 main and sub-groups (10 rats in each group). Control group, carbimazole group, levothyroxine group, BPF group, carbimazole group treated with levothyroxine and carbimazole group treated with BPF. At the end of experiments (60 days) rats were sacrificed and dissected; the blood was collected for determination of thyroid and male sex hormones. Also, the thyroid gland and testis were taken to histological study. The results indicated that, carbimazole group showed a highly significant decrease in thyroid hormones (T4, T3, Ft4 and Ft3) and male sex hormones (LH, FSH and testosterone), but a significant increase in TSH compared to control group. The results revealed that, treated groups with levothyroxine or BPF have significant increase in thyroid and male sex hormones and significant decreasein TSH. A significant improvement was detected in co-treated groups (hypothyroid groups) with levothyroxine or (BPF). Also, the present study showed a histopathological change in thyroid gland and testis of hypothyroid male rats. Conclusion Treated hypothyroid rats with levothyroxine as a drug and BPF as a natural product showed an improvement of these complications induced by carbimazole in thyroid gland and testis. Therefore, BPF may be benefical in treatment of hypothyroidism.

Sex Hormones, Growth Hormone, and the Cornea

The growth and maintenance of nearly every tissue in the body is influenced by systemic hormones during embryonic development through puberty and into adulthood. Of the ~130 different hormones expressed in the human body, steroid hormones and peptide hormones are highly abundant in circulation and are known to regulate anabolic processes and wound healing in a tissue-dependent manner. Of interest, differential levels of sex hormones have been associated with ocular pathologies, including dry eye disease and keratoconus. In this review, we discuss key studies that have revealed a role for androgens and estrogens in the cornea with focus on ocular surface homeostasis, wound healing, and stromal thickness. We also review studies of human growth hormone and insulin growth factor-1 in influencing ocular growth and epithelial regeneration. While it is unclear if endogenous hormones contribute to differential corneal wound healing in common animal models, the abundance of evidence suggests that systemic hormone levels, as a function of age, should be considered as an experimental variable in studies of corneal health and disease.

Sea Anemones Responding to Sex Hormones, Oxybenzone, and Benzyl Butyl Phthalate: Transcriptional Profiling and in Silico Modelling Provide Clues to Decipher Endocrine Disruption in Cnidarians

Endocrine disruption is suspected in cnidarians, but questions remain how occurs. Steroid sex hormones are detected in corals and sea anemones even though these animals do not have estrogen receptors and their repertoire of steroidogenic enzymes appears to be incomplete. Pathways associated with sex hormone biosynthesis and sterol signaling are an understudied area in cnidarian biology. The objective of this study was to identify a suite of genes that can be linked to exposure of endocrine disruptors. Exaiptasia diaphana were exposed to nominal 20ppb concentrations of estradiol (E2), testosterone (T), cholesterol, oxybenzone (BP-3), or benzyl butyl phthalate (BBP) for 4 h. Eleven genes of interest (GOIs) were chosen from a previously generated EST library. The GOIs are 17β-hydroxysteroid dehydrogenases type 14 (17β HSD14) and type 12 (17β HSD12), Niemann-Pick C type 2 (NPC2), Equistatin (EI), Complement component C3 (C3), Cathepsin L (CTSL), Patched domain-containing protein 3 (PTCH3), Smoothened (SMO), Desert Hedgehog (DHH), Zinc finger protein GLI2 (GLI2), and Vitellogenin (VTG). These GOIs were selected because of functional associations with steroid hormone biosynthesis; cholesterol binding/transport; immunity; phagocytosis; or Hedgehog signaling. Quantitative Real-Time PCR quantified expression of GOIs. In silico modelling utilized protein structures from Protein Data Bank as well as creating protein structures with SWISS-MODEL. Results show transcription of steroidogenic enzymes, and cholesterol binding/transport proteins have similar transcription profiles for E2, T, and cholesterol treatments, but different profiles when BP-3 or BBP is present. C3 expression can differentiate between exposures to BP-3 versus BBP as well as exposure to cholesterol versus sex hormones. In silico modelling revealed all ligands (E2, T, cholesterol, BBP, and BP-3) have favorable binding affinities with 17β HSD14, 17β HSD12, NPC2, SMO, and PTCH proteins. VTG expression was down-regulated in the sterol treatments but up-regulated in BP-3 and BBP treatments. In summary, these eleven GOIs collectively generate unique transcriptional profiles capable of discriminating between the five chemical exposures used in this investigation. This suite of GOIs are candidate biomarkers for detecting transcriptional changes in steroidogenesis, gametogenesis, sterol transport, and Hedgehog signaling. Detection of disruptions in these pathways offers new insight into endocrine disruption in cnidarians.

Associations Between Dietary Inflammatory Index and Sex Hormones Among 6- to 19-Year-Old Children and Adolescents in NHANES 2015–2016

ObjectivesThis study aimed to assess the relationship between dietary inflammatory index (DII) and sex steroids in children (6-11 years old) and adolescents (12-19 years old) in the U.S. National Health and Nutrition Examination Survey, 2015–2016.MethodsParticipants between the ages of 6-19 have 24-hour dietary intake data, serum sex hormones [total testosterone (TT), estradiol (E2)], and sex hormone-binding globulin (SHBG) available data (n = 1382). The free androgen index (FAI) is calculated as TT divided by SHBG and the ratio of TT to E2 (TT/E2). The constructed puberty state is defined as high levels of steroid hormones (TT≥50 ng/dL in men, E2≥20 pg/ml in women) or onset of menarche. Multiple linear regression analysis was stratified by gender-age and gender-pubertal status groups to evaluate the association between DII and sex hormone levels.ResultsAfter adjusting for covariates, the association between consecutive DII and sex hormone indicators by gender and age group. In male adolescents, DII was always negatively associated with TT (P-trend = 0.09), FAI (P-trend = 0.03) and E2 (P-trend = 0.01), and monotonically positively associated with SHBG (P-trend = 0.02).In female adolescents, with the increase of DII, a significant positive correlation with SHBG was observed (β 0.017, 95%CI: 0.009,0.053) (Table 3). Among female adolescents, a significant negative association between DII and TT and a significant positive association between SHBG were observed in this group. Moreover, DII was positively associated with SHBG of prepubertal males and negatively associated with FAI of prepubertal females.ConclusionsDII was associated with decreased levels of certain sex steroid hormones (TT, FAI, and E2) and increased levels of SHBG in adolescents or pubertal individuals, with the associations presenting somewhat sex-dependent pattern. However, there is little evidence that there is a significant association in children or prepubertal children. Further research needs to be carried out to verify our results.

Sex Hormone-Specific Neuroanatomy of Takotsubo Syndrome: Is the Insular Cortex a Moderator?

Takotsubo syndrome (TTS), a transient form of dysfunction in the heart’s left ventricle, occurs predominantly in postmenopausal women who have emotional stress. Earlier studies support the concept that the human circulatory system is modulated by a cortical network (consisting of the anterior cingulate gyrus, amygdala, and insular cortex (Ic)) that plays a pivotal role in the central autonomic nervous system in relation to emotional stressors. The Ic plays a crucial role in the sympathovagal balance, and decreased levels of female sex hormones have been speculated to change functional cerebral asymmetry, with a possible link to autonomic instability. In this review, we focus on the Ic as an important moderator of the human brain–heart axis in association with sex hormones. We also summarize the current knowledge regarding the sex-specific neuroanatomy in TTS.

Joint effect of particulate matter and cigarette smoke on women’s sex hormones

Background Although relationships between exposure to air pollution and reproductive health are broadly studied, mechanisms behind these phenomena are still unknown. The aim of the study was to assess whether exposure to particulate matter (PM10) and tobacco smoking have an impact on menstrual profiles of 17β-estradiol (E2) and progesterone (P) and the E2/P ratio. Methods Levels of sex hormones were measured daily in saliva during the entire menstrual cycle among 132 healthy, urban women. Exposure to smoking (active or passive) was assessed by questionnaire, whilst exposure to PM10 with municipal monitoring data. Results During the early luteal phase, profiles of E2 were elevated among women with higher versus lower exposure to PM10 (p = 0.02, post-hoc tests). Among those who were exposed versus unexposed to tobacco smoking, the levels of mean E2 measured during the entire cycle were higher (p = 0.02). The difference in mean E2 levels between the group of joint exposure (i.e. to high PM10 and passive or active smoking) versus the reference group (low PM10, no smoking) was statistically significant at p = 0.03 (18.4 vs. 12.4 pmol/l, respectively). The E2/P ratios were higher among women with higher versus lower exposure to PM10 and this difference was seen only in the early luteal phase (p = 0.01, exploratory post-hoc tests). Conclusions We found that PM10 and tobacco smoking affect ovarian hormones independently and do not interact with each other. Both exposures appear to have estrogenic effects even though women's susceptibility to these effects differs across the menstrual cycle. We propose that the hormonal mechanisms are involved in observed relationships between air pollution and smoking with women’s reproductive health.