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Concept: Estradiol


BACKGROUND: Estrogen has been reported to accelerate cutaneous wound healing. This research studies the effect of young coconut juice (YCJ), presumably containing estrogen-like substances, on cutaneous wound healing in ovairectomized rats. METHODS: Four groups of female rats (6 in each group) were included in this study. These included sham-operated, ovariectomized (ovx), ovx receiving estradiol benzoate (EB) injections intraperitoneally, and ovx receiving YCJ orally. Two equidistant 1-cm full-thickness skin incisional wounds were made two weeks after ovariectomy. The rats were sacrificed at the end of the third and the fourth week of the study, and their serum estradiol (E2) level was measured by chemiluminescent immunoassay. The skin was excised and examined in histological sections stained with H&E, and immunostained using anti-estrogen receptor (ER-alpha an ER-beta) antibodies. RESULTS: Wound healing was accelerated in ovx rats receiving YCJ, as compared to controls. This was associated with significantly higher density of immunostaining for ER-alpha an ER-beta in keratinocytes, fibroblasts, white blood cells, fat cells, sebaceous gland, skeletal muscles, and hair shafts and follicles. This was also associated with thicker epidermis and dermis, but with thinner hypodermis. In addition, the number and size of immunoreactive hair follicles for both ER-alpha and ER-beta were the highest in the ovx+YCJ group, as compared to the ovx+EB group. CONCLUSIONS: This study demonstrates that YCJ has estrogen-like characteristics, which in turn seem to have beneficial effects on cutaneous wound healing.

Concepts: Wound healing, Healing, Estradiol, Skin, Dermis, Epidermis, Sebaceous gland, Coconut water


A controlled release delivery system helps to overcome the problem of short life of the leutinizing hormone releasing hormone (LHRH) in blood and avoids use of multiple injections to enhance reproductive efficacy. Chitosan- and chitosan-gold nanoconjugates of salmon LHRH of desired size, dispersity and zeta potential were synthesized and evaluated at half the dose rate against full dose of bare LHRH for their reproductive efficacy in the female fish, Whereas injections of both the nanoconjugates induced controlled and sustained surge of the hormones with peak (P<0.01) at 24 hrs, surge due to bare LHRH reached its peak at 7 hrs and either remained at plateau or sharply declined thereafter. While the percentage of relative total eggs produced by fish were 130 and 67 per cent higher, that of fertilised eggs were 171 and 88 per cent higher on chitosan- and chitosan-gold nanoconjugates than bare LHRH. Chitosan nanoconjugates had a 13 per cent higher and chitosan gold preparation had a 9 per cent higher fertilization rate than bare LHRH. Histology of the ovaries also attested the pronounced effect of nanoparticles on reproductive output. This is the first report on use of chitosan-conjugated nanodelivery of gonadotropic hormone in fish.

Concepts: Hormone, Menopause, Luteinizing hormone, Estradiol, Follicle-stimulating hormone, Human chorionic gonadotropin, Gonadotropin, Hormones


Elevated estradiol levels are correlated with male infertility. Causes of hyperestrogenism include diseases of the adrenal cortex, testis or medications affecting the hypothalamus-pituitary-gonadal axis. The aim of our study was to elucidate the effects of estradiol treatment on testicular cellular morphology and function, with reference to the treatment regimen received. Testes samples (n = 9) were obtained post-orchiectomy from male-to-female transsexuals within the age range of 26-52 years. Each patient had a minimum of 1-6 years estradiol treatment. For comparison, additional samples were obtained from microscopically unaltered testicular tissue surrounding tumors (n = 7). The tissues obtained were investigated by stereomicroscopy, histochemistry, scanning electron microscopy (SEM) and immunohistochemistry. Our studies revealed that estradiol treatment significantly decreased the diameter of the seminiferous tubules (p < 0.05) and induced fatty degeneration in the surrounding connective tissue. An increase in collagen fiber synthesis in the extracellular matrix (ECM) surrounding the seminiferous tubules was also induced. Spermatogenesis was impaired resulting in mainly spermatogonia being present. Sertoli cells revealed diminished expression of estrogen receptor alpha (ERα). Both Sertoli and Leydig cells showed morphological alterations and glycoprotein accumulations. These results demonstrate that increased estradiol levels drastically impact the human testis.

Concepts: Testosterone, Testicle, Estradiol, Sertoli cell, Scanning electron microscope, Puberty, Male reproductive system, Leydig cell


Sex hormones fluctuate during the menstrual cycle. Evidence from animal studies suggests similar subtle fluctuations in hippocampal structure, predominantly linked to estrogen. Hippocampal abnormalities have been observed in several neuropsychiatric pathologies with prominent sexual dimorphism. Yet, the potential impact of subtle sex-hormonal fluctuations on human hippocampal structure in health is unclear. We tested the feasibility of longitudinal neuroimaging in conjunction with rigorous menstrual cycle monitoring to evaluate potential changes in hippocampal microstructure associated with physiological sex-hormonal changes. Thirty longitudinal diffusion weighted imaging scans of a single healthy female subject were acquired across two full menstrual cycles. We calculated hippocampal fractional anisotropy (FA), a measure sensitive to changes in microstructural integrity, and investigated potential correlations with estrogen. We observed a significant positive correlation between FA values and estrogen in the hippocampus bilaterally, revealing a peak in FA closely paralleling ovulation. This exploratory, single-subject study demonstrates the feasibility of a longitudinal DWI scanning protocol across the menstrual cycle and is the first to link subtle endogenous hormonal fluctuations to changes in FA in vivo. In light of recent attempts to neurally phenotype single humans, our findings highlight menstrual cycle monitoring in parallel with highly sampled individual neuroimaging data to address fundamental questions about the dynamics of plasticity in the adult brain.

Concepts: Combined oral contraceptive pill, Menopause, Estradiol, Menstrual cycle, Endometrium, Corpus luteum, Progesterone, Ovulation


Context:Testosterone (T) levels decline with age and lower T has been associated with increased mortality in aging men. However, the associations of its metabolites, dihydrotestosterone (DHT) and estradiol (E2), with mortality are poorly defined.Objective:We assessed associations of T, DHT, and E2 with all-cause and ischemic heart disease (IHD) mortality in older men.Participants:Participants were community-dwelling men aged 70 to 89 years who were residing in Perth, Western Australia.Main Outcome Measures:Plasma total T, DHT, and E2 were assayed using liquid chromatography-tandem mass spectrometry in early morning samples collected in 2001 to 2004 from 3690 men. Deaths to December 2010 were ascertained by data linkage.Results:There were 974 deaths (26.4%), including 325 of IHD. Men who died had lower baseline T (12.8 ± 5.1 vs 13.2 ± 4.8 nmol/L [mean ± SD], P = .013), DHT (1.4 ± 0.7 vs 1.5 ± 0.7 nmol/L, P = .002), and E2 (71.6 ± 29.3 vs 74.0 ± 29.0 pmol/L, P = .022). After allowance for other risk factors, T and DHT were associated with all-cause mortality (T: quartile [Q] Q2:Q1, adjusted hazard ratio [HR] = 0.82, P = .033; Q3:Q1, HR = 0.78, P = .010; Q4:Q1, HR = 0.86, P > .05; DHT: Q3:Q1, HR = 0.76, P = .003; Q4:Q1, HR = 0.84, P > .05). Higher DHT was associated with lower IHD mortality (Q3:Q1, HR = 0.58, P = .002; Q4:Q1, HR = 0.69, P = .026). E2 was not associated with either all-cause or IHD mortality.Conclusions:Optimal androgen levels are a biomarker for survival because older men with midrange levels of T and DHT had the lowest death rates from any cause, whereas those with higher DHT had lower IHD mortality. Further investigations of the biological basis for these associations including randomized trials of T supplementation are needed.

Concepts: Epidemiology, Death, Mass spectrometry, Testosterone, Estradiol, Ischemia, Dihydrotestosterone, Ischaemic heart disease


Alcohol (ethanol) and resistance exercise can independently affect circulating bioavailable testosterone concentration. PURPOSE: The purpose of this study was to examine the testosterone bioavailability and the anabolic endocrine milieu in response to acute ethanol ingestion following a bout of heavy resistance exercise. METHODS: Eight resistance trained men (mean ± SD: 25.3 ± 3.2 yrs, 87.7 ± 15.1 kg, 177 ± 7 cm) completed two identical acute heavy resistance exercise tests (AHRET: six sets of 10 repetitions of Smith machine squats) separated by 1 week. Post-AHRET participants consumed either 1.086 g of grain ethanol per kg lean mass (EtOH condition) or no ethanol (Placebo condition). Blood samples were collected immediately before exercise (PRE), immediately after exercise (IP), and every 20 min postexercise for 300 min. Samples following IP were pooled into phases (20-40 min, 60-120 min, and 140-300 min after exercise) and analyzed for total (TT) and free testosterone (FT), sex hormone binding globulin (SHBG), cortisol, and estradiol. RESULTS: Peak blood ethanol concentration (0.088 ± 0.015 g·dl) was achieved 60-90 min post-exercise. TT and FT was elevated significantly (p≤0.05) at IP for both conditions. At 140-300 min post-exercise TT, FT, and free androgen index were significantly higher for EtOH (TT: 22.5 ± 12.5 nmol·l ; FT: 40.5 ± 7.6 pmol·l) than for Placebo (TT: 13.9 ± 6.8 nmol·l; FT: 22.7 ± 10.0 pmol·l). No differences between conditions were noted for SHBG, Cortisol, or Estradiol. CONCLUSION: Post-exercise ethanol ingestion affects the hormonal milieu including testosterone concentration and bioavailability during recovery from resistance exercise.

Concepts: Hormone, Ethanol, Luteinizing hormone, Testosterone, Sex hormone-binding globulin, Estradiol, Adrenal cortex, Anabolic steroid


Objective:To investigate the influence of adiposity on patterns of sex hormones across the menstrual cycle among regularly menstruating women.Subjects:The BioCycle Study followed 239 healthy women for 1-2 menstrual cycles, with up to eight visits per cycle timed using fertility monitors.Methods:Serum estradiol (E2), progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) were measured at each visit. Adiposity was measured by anthropometry and by dual energy X-ray absorptiometry (DXA). Differences in hormonal patterns by adiposity measures were estimated using nonlinear mixed models, which allow for comparisons in overall mean levels, amplitude (i.e., lowest to highest level within each cycle) and shifts in timing of peaks while adjusting for age, race, energy intake and physical activity.Results:Compared with normal weight women (n=154), obese women (body mass index (BMI) 30 kg m(-2), n=25) averaged lower levels of progesterone (-15%, P=0.003), LH (-17%, P=0.01), FSH (-23%, P=0.001) and higher free E2 (+22%, P=0.0001) across the cycle. To lesser magnitudes, overweight women (BMI: 25-30, n=60) also exhibited differences in the same directions for mean levels of free E2, FSH and LH. Obese women experienced greater changes in amplitude of LH (9%, P=0.002) and FSH (8%, P=0.004), but no differences were observed among overweight women. Higher central adiposity by top compared to bottom tertile of trunk-to-leg fat ratio by DXA was associated with lower total E2 (-14%, P=0.005), and FSH (-15%, P=0.001). Peaks in FSH and LH occurred later (∼0.5 day) in the cycle among women with greater central adiposity.Conclusion:Greater total and central adiposity were associated with changes in mean hormone levels. The greater amplitudes observed among obese women suggest compensatory mechanisms at work to maintain hormonal homeostasis. Central adiposity may be more important in influencing timing of hormonal peaks than total adiposity.

Concepts: Obesity, Menopause, Estrogen, Luteinizing hormone, Body mass index, Estradiol, Menstrual cycle, Follicle-stimulating hormone


In men, obesity and the metabolic syndrome are accompanied by decreased testosterone levels, but little is known about the associations between visceral adipose tissue (VAT), VAT-related inflammation and sex steroids.

Concepts: Obesity, Insulin resistance, Adipose tissue, Testosterone, Estradiol, Cytochrome P450, Steroid, Adiponectin


Sertoli cell proliferation is prolonged in neonatal boars treated with the aromatase inhibitor letrozole, but porcine testicular aromatase synthesizes a potent, non-aromatizable androgen,1-hydroxytestosterone, as well as estradiol. Therefore, experiments were conducted to determine whether the Sertoli cell proliferative response to letrozole is due to a loss of estrogen or a loss of androgen signaling. Littermate boars were treated with letrozole, the estrogen receptor blocker ICI 182,780, or vehicle, from 1 week of age and testes collected at 6.5 weeks. Sertoli cell number was increased 30% by letrozole or ICI 182,780 compared with vehicle. Neither treatment affected testosterone, gonadotropins or prolactin. We conclude that Sertoli cell proliferation in neonatal boars is restricted by the local activation of estrogen receptors. The response to letrozole is apparently not mediated by the novel capacity of the porcine gonadal aromatase for 1-hydroxytestosterone but by estradiol synthesis; therefore, aromatase inhibition may have similar effects on Sertoli cell proliferation in other species.

Concepts: Estrogen, Estrogen receptor, Testosterone, Testicle, Estradiol, Steroid, Sertoli cell, Aromatase


Various ovarian substances regulate the secretion of gonadotrophins during the menstrual cycle, but there are still several unclarified issues. The aim of this study was to investigate the positive feedback effect of progesterone during the immediate period following ovariectomy. Experiments were performed in 12 normally cycling women (aged 39-49 years). Following abdominal hysterectomy plus bilateral ovariectomy performed on cycle day 3 (day 0), the women received either estradiol via skin patches (days 0-7, n = 6, group 1) or estradiol as above plus vaginal progesterone (days 1-7, n = 6, group 2). Serum estradiol values increased similarly in the two groups. After the operation, serum progesterone levels decreased significantly in group 1, while in group 2 they remained stable becoming higher than in group 1 (p < 0.05). An LH and an FSH surge occurred in group 2 with the values after the peak returning to the pre-surge baseline. In contrast, in group 1 LH and FSH levels following an initial decrease, increased gradually until the end of the experiment. These results demonstrate that, despite a variable response to estrogens, the positive feedback effect of progesterone remained intact immediately after ovariectomy in women. It is suggested that it is the combining action of estradiol and progesterone that can ensure the expression of a positive feedback mechanism in women.

Concepts: Combined oral contraceptive pill, Menopause, Estrogen, Estradiol, Menstrual cycle, Progesterone, Feedback, Positive feedback