Prolactin promotes a partial recovery from the atrophy of both male and female gerbil prostates caused by castration

Background The male and female prostates are controlled by steroid hormones, suffering important morphological and physiological changes after castration. Prolactin is involved in the regulation of the male prostate, having already been identified in the tissue, acting through its receptor PRLR. In the Mongolian gerbil, in addition to the male prostate, the female prostate is also well developed and active in its secretion processes. The aim of the present study was to evaluate the effects of exposure to exogenous prolactin in the prostate of both intact and castrated male and female gerbils in order to establish if prolactin administration can sustain prostate cell activity in conditions of sexual hormone deprivation. Methods The morphological analyses were performed by biometric analysis, lesion histological analysis and morphometric-stereological aspects. In addition, immune-cytochemical tests were performed for prolactin and its receptor, as well as for the receptors of androgen and oestrogen and serum prolactin dosage. All data were submitted to ANOVA or Kruskal-Wallis tests for comparison between groups. P < 0.05 was considered to be statistically significant. Results The results showed a strong influence of prolactin on the morphology of the prostate, with the development of important epithelial alterations, after only 3 days of administration, and an expressive epithelial cell discard process after 30 days of administration. Prolactin acts in synergy with testosterone in males and mainly with oestrogens in females, establishing different steroid hormonal receptor immunoreactivity according to sex. It was also demonstrated that prolactin can assist in the recovery from some atrophic effects caused in the gland after castration, without causing additional tissue damage. Conclusions The prolactin and its receptor are involved in the maintenance of the homeostasis of male and female gerbils, and also cause distinct histological alterations after exogenous exposure for 3 and 30 days. The effects of prolactin are related to its joint action on androgens and oestrogens and it can also assist in the recovery from the atrophic effects of castration.

Exercise-Induced Muscle Damage in Postmenopausal Well-Trained Women

Background: Sex hormone deprivation derived from menopause may affect exercise-induced muscle damage (EIMD). No studies have previously evaluated this response between postmpenopausal and premenopausal eumenorrheic women over the menstrual cycle. Hypothesis: Postmenopausal women will present higher EIMD markers than premenopausal women, especially in comparison with the menstrual cycle phases where sex hormone concentrations are higher. Study Design: Cross-sectional study. Level of Evidence: Level 3. Methods: Thirteen postmenopausal and 19 eumenorrheic women, all of them resistance-trained, performed an eccentric squat-based exercise. The postmenopausal group performed 1 bout of exercise, while the eumenorrheic group performed 3 bouts coinciding with the early follicular, late follicular, and mid-luteal phases ot their menstrual cycle. Muscle soreness, countermovement jump, creatine kinase (CK), myoglobin, lactate dehydrogenase, interleukin-6, tumor necrosis factor-α, and C-reactive protein were evaluated before and postexercise. Results: The expected differences in sex hormones were observed between groups ( P < 0.001) according to their reproductive status. Postexercise increases in CK, myoglobin, and muscle soreness (168.2 ± 45.5 U/L, 123.1 ± 41.5 µg/L, and 20.7 ± 21.3 mm, respectively) were observed in comparison with baseline (136.2 ± 45.5 U/L, 76.9 ± 13.8 µg/L, and 2.7 ± 4.2 mm, respectively). Myoglobin values at baseline in postmenopausal women were higher compared with premenopausal women in the aforementioned menstrual cycle phases, respectively (62.8 ± 8.2, 60.4 ± 7.2, and 60.1 ± 10.6 µg/L; P < 0.001 for all comparisons), which was supported by large effect sizes (0.72-1.08 standardized d units). No postexercise differences were observed between groups in any markers ( P > 0.05). Conclusion: Despite higher resting levels of myoglobin and lower strength values in postmenopausal than in premenopausal women, EIMD was similar between both reproductive profiles. This suggests a potential benefit of being physically active despite aging and sex hormone deprivation. Clinical Relevance: Sex hormone deprivation derived from menopause seems not to influence muscle damage reponse to eccentric exercise in resistance-trained postmenopausal women.

Should We Reconsider the Necessity of a Refinement of Prostate Cancer Risk Classification and Radiotherapy Treatment Strategy? Experiences from a Retrospective Analysis of Data from a Single Institution

Background: Radiation therapy has undergone significant technical development in the past decade. However, the complex therapy of intermediate-risk patients with organ-confined prostate carcinoma still poses many questions. Our retrospective study investigated the impact of selected components of the treatment process including radiotherapy, hormone deprivation, risk classification, and patients’ response to therapy. Methods: The impact of delivered dose, planning accuracy, duration of hormone deprivation, risk classification, and the time to reach prostate-specific antigen (PSA) nadir state were analyzed among ninety-nine individuals afflicted with organ-confined disease. Progression was defined as a radiological or biochemical relapse within five years from radiotherapy treatment. Results: We found that 58.3% of the progressive population consisted of intermediate-risk patients. The progression rate in the intermediate group was higher (21.9%) than in the high-risk population (12.1%). Dividing the intermediate group, according to the International Society of Urological Pathology (ISUP) recommendations, resulted in the non-favorable subgroup having the highest rate of progression (33.3%) and depicting the lowest percentage of progression-free survival (66.7%). Conclusion: Extended pelvic irradiation on the regional lymph nodes may be necessary for the ISUP Grade 3 subgroup, similarly to the high-risk treatment. Therapy optimization regarding the intermediate-risk population based on the ISUP subgrouping suggestions is highly recommended in the treatment of organ-confined prostate cancer.

Prostate cancer and therapeutic challenges

Prostate cancer (PC) is the most prevalent type of cancer in men worldwide. In Saudi Arabia, the rate of PC is increasing annually. The sex steroid hormones androgens and their receptors have critical roles in PC development and progression. Additionally, apoptosis-related proteins such as heat-shock proteins are vital molecules in PC development. Steroid hormone-deprivation therapies remain the essential treatment for patients with metastatic PCs; however, acquired resistance to hormone deprivation and the transition to PC androgen independence is a major health obstacle. In this review, we aim to detail the roles of androgens, androgen receptors and sex steroid hormones in inducing apoptosis in PC.

Abstract 14712: Cardiometabolic Differences Between Male and Female Obese-insulin Resistant Rats Following Sex Hormone Deprivation

Introduction: Male gender and menopause increase the risk for cardiovascular incidence. However, less is known about gender differences in cardiometabolic disorders, particularly under obese-insulin resistant and sex hormone-deprived conditions. Hypothesis: Male have worse cardiometabolic disorders than female under obese-insulin resistant and sex hormone-deprived conditions. Methods: Adult Wistar rats of both sexes (n=20) were randomly assigned into four groups (n = 5/group): male normal diet sham (M-NDS), male high fat-diet with orchiectomy (M-HFO), female normal diet sham (F-NDS) and female high fat-diet with ovariectomy (F-HFO). Rats were fed either a normal diet (19.77% of energy fat) or a high-fat diet (57.60% of energy fat) for 12 weeks following the induction of sex hormone deprivation by either bilateral orchiectomy or ovariectomy. Temporal determinations of metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function at 4, 8, and 12 weeks were done after starting each feeding program. Results: Insulin resistance was initially observed after 8 weeks of high-fat diet consumption in both M-HFO and F-HFO groups. In addition, M-HFO had depressed HRV, impaired LV performance indicated by decreased ejection fraction (%EF) and cardiac mitochondrial dysfunction indicated by increased mitochondrial ROS level, depolarization and swelling, as early as week 4, whereas F-HFO exhibited them at week 8 or 12. Moreover, at week 12, M-HFO have worse cardiometabolic disorders than F-HFO, particularly %EF and HRV. Conclusions: Under sex hormone-deprived condition, male are generally more susceptible to cardiometabolic disorders and cardiac mitochondrial dysfunction, especially in the presence of obese-insulin resistant condition.

Age-dependent cardiac remodelling – role of sex hormones

Background While cardiovascular mortality in women has exceeded those in men, women continue to be underrepresented in cardiovascular clinical trials. Further, preclinical experiments are predominantly conducted in male animals, rendering sex-specific variables contributing to cardiovascular disease largely unknown. As age and menopause remain to be key risk factors for cardiovascular disease in women, the aim of this study was to identify key variables of cardiac remodelling in the aging female and male heart, as well as to assess effects of sex hormone deprivation on left ventricular (LV) morphology, LV function and cardiac sympathetic activity. Materials and methods Gonadectomized and sham-operated FVB/N mice of both sexes were subjected to positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging at the age of 4 (young cohort) and 20 (aged cohort) months (total n=123, 55% females). Following tail-vein injection of [11C]meta-hydroxynorephedrine ([11C]mHED), a widely used PET probe in preclinical and clinical assessment of cardiac sympathetic integrity, animals were scanned and cardiac sympathetic outflow was derived from myocardial [11C]mHED uptake. Cardiac parameters including LV volumes and left ventricular ejection fraction (LVEF) were obtained from electrocardiogram (ECG)-gated CMR imaging. Results and discussion A significant increase of LVEF was observed in aging females (p=0.012, Figure 1), but not in males. The latter was not associated with a higher cardiac output, and was a consequence of reduced LV end-systolic volumes (p=0.008), unveiling a substantial reduction of size in the aging female heart. As this age-dependent observation was not present in gonadectomized animals (p=0.414), the lack of growth-stimulating estrogen might account for reduction of cardiac size in aging females. Thus, despite a significantly heightened body weight, female heart size is reduced with age. Accordingly, sufficient cardiac output was maintained via increased heart rate (p=0.005) and cardiac sympathetic activity (p=0.040, Figure 1). Gonadectomy accelerated age-dependent changes in LV morphology and function in female mice. While sex hormone deprivation blunted cardiac sympathetic activity and norepinephrine levels in male mice, an opposite trend was observed in females. Conclusion Despite increasing body weight with age, aged female and male hearts maintain a stable circulatory blood supply, however, by distinct mechanisms. While the “shrinking” female heart requires an increased heart rate and cardiac sympathetic activity to compensate for smaller ventricular volumes, aging males maintain cardiac size. Importantly, sex hormone deprivation at a young age accelerates age-dependent changes in LV morphology and function in female mice, but not in male mice. The increased sympathetic activity reflects a higher stress level in aged females that might expose them to a higher cardiac vulnerability at postmenopausal age. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation; Swissheart Foundation

Preliminary Evidence of the role of estrogen and tamoxifen-induced regulation of complement proteins in rat hippocampus

Effects of Estrogen (E2) is widespread in the human body; still, an unresolved paradox. Neurodegeneration and neuroinflammation are inherently associated with age progression, debilitating by hormone deprivation, especially in female. Senescent cells accumulate with age and promote tissue deterioration in the body system. Neurodegenerative diseases drive a healthy life towards to morbidity and feebleness; despite the different etiology, uncontrolled inflammation is one of the significant causals factors. We here used post-menopausal model (ovariectomized female rat), E2 replenishment therapy reduces the expression of inflammatory mediators, such as complement proteins (C3, C1q, and C3aR) in these animals.E2 therapy could limit the ovariectomy-induced increase of inflammatory events in brain regions such as the hippocampus. Also, the duration of hormone deprivation could be a determinant for the intensity of the anti-inflammatory actions of estrogen. On the whole, considerable evidence, including that from the present study supports the view that complement biosynthesis, which plays a significant role in phagocytosis of cellular debris and synaptic pruning of postnatal neural circuits goes uncontrolled and could be the inducing factor for enhanced neurodegeneration following hormone deprivation.