Exogenous Hormone Administration Research Articles

5114 Establishment of Thyroid Storm Mouse Model and Therapeutic Effects of Ghrelin

Abstract Disclosure: C. Kurimoto: None. Y. Furukawa: None. T. Akamizu: None. A. Doi: None. K. Takeshima: None. S. Morita: None. H. Iwakura: None. H. Ariyasu: None. H. Furuta: None. M. Nishi: None. T. Matsuoka: None. Context: Thyroid storm (TS), a life-threatening condition that can damage multiple organs, is caused by a combination of thyrotoxicosis and severe physical stresses. Infection is the most common triggering factor. Hypercytokinemia is a suggested background, but the pathological condition is unclear and there are no appropriate animal models. Further, TS has limited therapeutic options. Objectives: We aimed to confirm the hypercytokinemia in patients with TS, establish a TS model mouse by triiodothyronine and lipopolysaccharide administration, and explore the therapeutic effects of ghrelin on TS. Methods: We evaluated serum IL-6 levels as a representative marker of hypercytokinemia in patients with TS. As a TS model, C57BL/6 mice were titrated with triiodothyronine and lipopolysaccharide to develop a lethal model with approximately 30% survival at 24 hours. We assessed the survival ratio, mouse sepsis scores and blood biomarkers (IL-6, metanephrine, alanine aminotransferase) and evaluated the effects of ghrelin on these parameters. Results: Serum IL-6 was increased in patients with TS compared with those with Graves' disease without TS (55.7 ± 69.0 vs. 3.13 ± 1.41 pg/mL, P < .05, n=4 each). Next, we titrated the doses of T3 and LPS, aiming to achieve a survival rate of approximately 30% at 24 hours after administration. Two out of five mice in the T3 3.0 mg/kg group died, while none of the eight mice in the T3 1.0 mg/kg group died. Therefore, we determined that the appropriate T3 dose for the TS mouse model is 1.0 mg/kg, which is not lethal when administered alone. In the T3 1.0 mg/kg group (n=8), serum FT3 levels were approximately three times higher (15.3 ± 4.5 vs. 4.5 ± 0.7pg/ml) than those in the control group (n=8). Next, different doses of LPS was added to the T3 group. Survival at 24 hours post-dose was 60% in the T3 + LPS 0.2 mg/kg group (n=5) and 33% in the T3 + LPS 0.5 mg/kg group (n=5), while survival was 100% in the LPS 0.5 mg/kg alone group (n=5),. Based on these findings, the dosage for the murine TS model was determined to be “triiodothyronine 1.0 mg/kg and lipopolysaccharide 0.5 mg/kg”. This TS model group had increased mouse sepsis score, serum IL-6, metanephrine and alanine aminotransferase. In this model, the ghrelin at 300 µg/kg improved the survival rate to 66.7% (P < .01, vs. 0% [saline-treated group]) as well as the mouse sepsis score, and it decreased the serum IL-6 and metanephrine. Conclusion: We confirmed the hypercytokinemia in patients with TS. Next, we established a lethal model simulating TS by inducing “thyrotoxicosis” by exogenous administration of thyroid hormones, and by inducing “sepsis” by intraperitoneal administration of LPS. The model mice exhibited similar pathophysiological status to human TS associated with induction of serum IL-6 and other biomarkers, which were improved by ghrelin. Presentation: 6/1/2024

Development and characterization of a novel variant of long-acting bovine follicle-stimulating hormone (brscFSH)

Assisted reproduction is a key aspect of modern animal breeding, providing valuable assistance in improving breeding programs. In this field, the administration of exogenous hormones, such as follicle-stimulating hormone (FSH), plays a crucial role in the induction of multiple ovulations. However, commercial FSH used in veterinary practice has been derived primarily from pituitary glands, obtained mostly from pigs for nearly four decades. Although these hormones have contributed significantly to the advancement of assisted reproductive techniques, they have certain limitations that warrant further improvements. These limitations include contamination with luteinizing hormone (LH), the potential risk of pathogen contamination, the potential to trigger an immune response in non-pig species, and the short half-life in circulation, requiring the implementation of complex 8-dose superovulation schedules. Our research team has developed and characterized a new variant of bovine follicle-stimulating hormone (bscrFSH) to address these limitations. The new hormone is produced recombinantly in CHO cell cultures, with a specific productivity of about 30 pg/cell/day. The bscrFSH can be purified to a high purity of 97 % using a single step of immobilized metal affinity chromatography (IMAC). N-glycan analysis of bscrFSH showed that approximately 74 % of the glycans corresponded to charged structures, including mono-, di-, tri-, and tetra-sialylated glycans. Superovulation trials conducted in cattle revealed that bscrFSH, administered at a total dose of about 0.5 μg per kg of body weight, using a decrescent schedule of 4 doses with 24-h intervals, resulted in an average yield of 8–12 transferable embryos per animal. Further research is required; however, the preliminary findings indicate that bscrFSH, currently packaged under the provisional brand name of Cebitropin B, holds potential as a commercial product for assisted reproduction in ruminants.

PbWRKY18 promotes resistance against black spot disease by activation of the chalcone synthase gene PbCHS3 in pear

Flavonoids are plant pigments that play a major role in plant defense and have significant health benefits to humans. Chalcone synthase (CHS) is an important enzyme in flavonoid biosynthesis and investigation transcription factors (TFs) regulating its expression and downstream targets is critical to understanding its mechanism. Here, a novel TF, PbWRKY18, was isolated from the pear Pyrus betulaefolia. Its expression was evaluated in various tissues by RT-PCR, particularly in response to Alternaria alternata, the pathogen responsible for black spot disease, and exogenous hormone administration. The PbWRKY18 protein was primarily found in the nucleus where it regulated transcriptional activity. Yeast one-hybrid and dual-luciferase reporter assays showed a strong association between PbWRKY18 and the PbCHS3 promoter, which drives PbCHS3 expression. It was also found that PbCHS3 was critical for the development of resistance against black spot disease. In addition, PbWRKY18 was found to significantly increase the expression of PbCHS3 and salicylic acid-related genes, as well as defense enzyme activity and tolerance to black spot disease. PbWRKY18 or PbCHS3 knockdown in pear attenuates resistance to Alternaria alternata. In summary, the study identified a novel WRKY18-CHS3 axis involved in resistance against black spot disease in pear.

Prenatal cortisol exposure impairs adrenal function but not glucose metabolism in adult sheep.

Adverse environmental conditions before birth are known to programme adult metabolic and endocrine phenotypes in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared with saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline-treated group. The results show that cortisol overexposure before birth programmes pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges.

Exogenous growth hormone administration during total sleep deprivation changed the microRNA-9 and dopamine D2 receptor expressions followed by improvement in the hippocampal synaptic potential, spatial cognition, and inflammation in rats.

Disorders caused by total sleep deprivation can be modulated by the administration of growth hormone, which could affect the expression of microRNA-9 and dopamine D2 receptor expressions followed by improvement in the hippocampal synaptic potential, spatial cognition, and inflammation in rats. The present study aimed to elucidate the putative effects of exogenous growth hormone (GH) against total sleep deprivation (TSD)-induced learning and memory dysfunctions and possible involved mechanisms. To induce TSD, rats were housed in homemade special cages equipped with stainless steel wire conductors to induce general and inconsistent TSD. They received a mild repetitive electric shock to their paws every 10 min for 21 days. GH (1 mg/kg, sc) was administered to adult young male rats once daily for 21-day-duration induction of TSD. Spatial learning and memory performance, inflammatory status, microRNA-9 (miR-9) expression, dopamine D2 receptor (DRD2) protein level, and hippocampal histological changes were assayed at scheduled times after TSD. The results indicated that TSD impaired spatial cognition, increased TNF-α, decreased level of miR-9, and increased DRD2 levels. Treatment with exogenous GH improved spatial cognition, decreased TNF-α, increased level of miR-9, and decreased DRD2 levels after TSD. Our findings suggest that GH may play a key role in the modulation of learning and memory disorders as well as the ameliorating abnormal DRD2-related functional disorders associated with miR-9 in TSD.

Recombinant anti-Mullerian hormone treatment attenuates primordial follicle loss after ovarian cryopreservation and transplantation.

The foremost drawback of ovarian tissue cryopreservation and re-transplantation (OTCT) technique is the rapid loss of the primordial follicle (PF) pool. In recent studies, we have demonstrated that post-transplantation burnout of the PFs occurs due to the altered expression of the activatory and inhibitory proteins that control PF reserve, and rapamycin prevented it. Here, we investigated whether anti-Mullerian hormone administration in the bilateral oophorectomy and transplantation group and internal AMH in the unilateral oophorectomy and transplantation group protect follicle reserve by regulating the expression of the molecules that control follicle growth after OTCT in mice. After 14days of OTCT, PF reserve is significantly reduced in both unilateral oophorectomy and transplantation and bilateral oophorectomy and transplantation groups, while anti-Mullerian hormone treatment attenuates PF loss after bilateral oophorectomy and transplantation. The expression of KitL, Bmp-15, and p27 decreased after unilateral oophorectomy and transplantation and bilateral oophorectomy and transplantation, yet recombinant anti-Mullerian hormone treatment did not restore the expression of these proteins in the BLO-T group. Exogenous recombinant anti-Mullerian hormone administration in the BLO-T group preserved the expressions of Tsc1 and Gdf-9 in PF and p-s6k and Gdf-9 in growing follicles after OTCT. Nonetheless, recombinant anti-Mullerian hormone administration did not affect granulosa cell proliferation and death rates in the growing follicles. These findings suggest a novel hormonal replacement strategy for fertility preservation by restoring anti-Mullerian hormone to regulate Tsc1 and p-s6k, thereby linking this hormone with the mTOR pathway and Gdf-9 signaling.

Biocompatible polymeric microparticles serve as novel and reliable vehicles for exogenous hormone manipulations in passerines

The administration of exogenous hormones emerged as an essential tool for field studies in endocrinology. However, working with wild animals remains challenging, because under field conditions not every available method meets the necessary requirements. Achieving a sustained elevation in hormone levels, while simultaneously minimising handling time and invasiveness of the procedure is a difficult task in field endocrinology.Facing this challenge, we have investigated the suitability of biocompatible polymeric microparticles, a novel method for drug-administration, as a tool to manipulate hormones in small songbirds. We chose the insulin-like growth factor-1 (IGF-1) as target hormone, because it receives great interest from the research community due to its important role in shaping life-history traits. Moreover, its short half-life and hydrophilic properties imply a major challenge in finding a suitable method to achieve a sustained, systemic long-term release. To study the release kinetics, we injected either IGF-1 loaded polylactic-co-glycolic acid (PLGA) microparticles or dispersion medium (control group) in the skin pocket of the interscapular region of captive bearded reedlings (Panurus biarmicus). We collected blood samples for 7 consecutive days plus an additional sampling period after two weeks and complemented these with an in vitro experiment.Our results show that in vitro, PLGA microparticles allowed a stable IGF-1 release for more than 15 days, following a burst release at the beginning of the measurement. In vivo, the initial burst was followed by a drop to still elevated levels in circulating IGF-1 until the effect vanished by 16 days post-treatment.This study is the first to describe the use of PLGA-microparticles as a novel tool for exogenous hormone administration in a small passerine. We suggest that this method is highly suitable to achieve the systemic long-term release of hydrophilic hormones with short half-life and reduces overall handling time, as it requires only one subcutaneous injection.

FERTILITY PRESERVATION TECHNIQUES WITH OR WITHOUT OVARIAN STIMULATION DO NOT CHANGE DISEASE-FREE SURVIVAL OF YOUNG BREAST CANCER PATIENTS

Fertility is often impaired in young women treated for breast cancer (BC). Therefore, fertility preservation (FP) has become a major issue in this population. Cryopreservation of oocytes or embryos after controlled ovarian hyperstimulation (COH) represents the most established method in this clinical situation. However, the hormonal consequences of COH protocols still raise safety concerns, often leading oncologists to contraindicate the use of this FP technique. Although alternative FP options without exogenous hormone administration may be considered, they remain suboptimal for treating the putative future infertility.

Women's experiences of infertility after the Holocaust

Nuremburg trial evidence demonstrated that Nazis sought methods of mass sterilization of Jewish women. Immediately upon arrival at the concentration camps, over 98% of women stopped menstruating. There has been minimal investigation as to the cause(s) of amenorrhea, beyond malnutrition and trauma. The major objectives of this article are to 1) provide an alternate hypothesis to explain women's amenorrhea, i.e., surreptitious administration of exogenous hormones to women; 2) detail survivors' reproductive histories so as to demonstrate long-term sequellae, especially pregnancy losses; 3) provide women's subjective narratives of the short- and long-term experience of reproductive losses; 4) link women's amenorrhea, subsequent primary and secondary infertility and the evidence for the hypothesized causal mechanism, i.e., the administration of sex steroids which might have led to both immediate and long-term reproductive impacts. We conducted telephone interviews from 2018 to 2021 with Holocaust survivors internationally in 4 languages. We collected 93 testimonies from female Holocaust survivors (average age 92.5) or offspring who could provide complete reproductive histories for survivors. The interviews focused on reproductive histories, including amenorrhea beginning in 1942–45, subsequent attempts to conceive, numbers of pregnancies, miscarriages and stillbirths. Ninety-eight percent of women interviewed were unable to conceive or carry to term their desired number of children. Of 197 confirmed pregnancies, at least 48 (24.4%) ended in miscarriages, 13 (6.6%) in stillbirths and 136 (69.0%) in live births. The true number of pregnancy losses is likely much higher. Only 15/93 (16.1%) of women were able to carry more than two babies to term, despite most wanting more children desperately. Amenorrhea among Jewish women arriving at concentration camps was too uniform and sudden to be effected only by trauma and/or malnutrition. Survivors' narratives and historical evidence suggest the role of exogenous hormones, administered without women's knowledge to induce amenorrhea as well as subsequent primary and secondary infertility.

Harnessing the value of reproductive hormones in cattle production with considerations to animal welfare and human health.

The human population is ever increasing while the quality and quantity of natural resources used for livestock production decline. This calls for improved product efficiency and the development of improved and sustainable cattle production methods to produce higher quality products to satisfy the demands of both the modern and transient world. The goal of this review was to summarize the interactions, challenges, and opportunities in cattle production relating to their endocrine system, and how reproductive hormones and others impact economically important traits, animal welfare, and human health. A comprehensive literature search was conducted with a focus on analysis of natural hormones and the use of exogenous hormone administration for reproduction, growth, and development of beef and dairy cattle. Hormones regulate homeostasis and enhance important traits in cattle, including fertility, growth and development, health, and the production of both meat and milk products. Reproductive hormones such as testosterone, estradiol, progesterone, and related synthetics like trenbolone acetate and zeranol can be strategically utilized in both beef and dairy cattle production systems to enhance their most valuable traits, but the impact of these substances must account for the welfare of the animal as well as the health of the consumer. This scientific review provides a comprehensive analysis of the bovine endocrine system's impact on food animals and product quality which is vital for students, researchers, livestock producers, and consumers. Although important advances have been made in animal science and related technological fields, major gaps still exist in the knowledge base regarding the influence of hormones on the production and welfare of food animals as well as in the public perception of hormone use in food-producing animals. Filling these gaps through transformative and translational research will enhance both fundamental and applied animal science to feed a growing population.

O-195 Disease-free survival is not impacted by fertility preservation techniques for breast cancer women

Abstract Study question Do fertility preservation (FP) strategies using ovarian stimulation or not, impact long-term disease-free survival of breast cancer (BC) patients? Summary answer The disease-free survival of BC patients is not impacted by FP techniques whatever the timing of chemotherapy (neoadjuvant /adjuvant) and the use of ovarian stimulation. What is known already Fertility is often impaired in young women treated for BC. Therefore, FP has become a major issue in this population. Cryopreservation of oocytes or embryos after controlled ovarian hyperstimulation (COH) represents the most established method in this clinical situation. However, the hormonal consequences of COH protocols still raise safety concerns, often leading oncologists to contraindicate the use of this FP technique. Although alternative FP options without exogenous hormone administration may be considered, they remain suboptimal for treating the putative future infertility. Study design, size, duration Retrospective bicentric cohort study including including 740 BC women, 18-43 years of age, referred for FP between 2013 and 2019. Participants/materials, setting, methods Overall, 328 underwent at least one ovarian stimulation cycle (STIM group) and 412 had a technique without hormonal administration (No STIM group). Log Rank test was used to compare both groups and Cox proportional-hazard model was applied for multivariable analyses. Main results and the role of chance Women of the No STIM group were significantly younger and present with more severe disease. Follow-up data for recurrences were available for 80.9% of the cohort and the median time to follow-up was 4.2 [2.9-5.8] vs. 5.6 [4.1-6.7] years between STIM and No STIM group (p < 0.0001). According to log-rank test, the risk of recurrence did not differ between the two groups (p = 0.09) even after adjustment on age, SBR grade, triple negative status or type of planned chemotherapy. Limitations, reasons for caution The retrospective nature of the study represents the main limitation. The median follow-up of 4.2 to 5.6 years, might be considered short to assess the long-term safety of FP techniques. The heterogeneity between oncological centers regarding the use of COH and specific protocols may lalso be a reason for caution. Wider implications of the findings Our findings provide reassuring safety data on the use COH for FP in BC patients, whatever the timing of chemotherapy. However, further investigations with a longer follow-up are needed to definitely consider COH safe in particular in neoadjuvant situations. In addition, the benefit of letrozole supplementation during COH requires confirmation. Trial registration number Not applicable

P-333 The influence of hormonal stimulation on uterine peristalsis measured by ultrasound speckle tracking in women with IVF/ICSI treatment compared to normal ovulating women

Abstract Study question To investigate possible effects of ovarian stimulation during IVF/ICSI on uterine peristalsis features using ultrasound speckle tracking compared to normal ovulating women. Summary answer Patients with a normal uterus treated with exogenous hormones during IVF/ICSI treatment show significantly increased contraction amplitude and power parameters compared to normal ovulating women. What is known already Uterine peristalsis plays a role in procreation. Subjective visual inspection of uterine peristalsis is extensively researched throughout the menstrual cycle. Studies on uterine peristalsis in IVF/ICSI patients show higher frequency of uterine contractions during the periovulatory phase. Recently, a new automated quantitative method was validated to objectively analyse uterine strain using speckle tracking. Besides objective insight in frequency, also information on amplitude, power and coordination of motion is available. The effect of exogenous hormones on uterine contraction features has not objectively been studied using this new method. Study design, size, duration This multicentre prospective observational cohort study was performed between 2020 and 2022 in the Catharina Hospital in Eindhoven, the Netherlands, Embryolab Fertility Centre in Thessaloniki, Greece and University of Naples, Federico II in Naples, Italy. 30 normal ovulating patients served as controls. The primary outcomes were the contraction features frequency, amplitude, direction, velocity, power and coordination in women undergoing IVF/ICSI on the day of follicle aspiration compared to controls on cycle day 9 – 14. Participants/materials, setting, methods 19 women undergoing IVF/ICSI were included regardless of the treatment cycle number and stimulation protocol. Indication for IVF/ICSI treatment was male subfertility (n = 8), idiopathic subfertility (n = 5), tubal factor (n = 2), primary ovarian insufficiency (n = 2) or combined (n = 2), all women had normal uteri on transvaginal ultrasound. The control group consisted of 30 healthy pre-menopausal women with normal uteri on ultrasound and spontaneous regular cycles. Main results and the role of chance Each patient underwent a 2.5 – 4 minute transvaginal ultrasound of the uterus in mid-sagittal plane. The various contraction features were extracted using a quantitative dedicated speckle tracking algorithm analysis studying motion of the subendometrial junctional zone. Mean age of IVF/ICSI patients was 32.7 years and mean BMI was 25.6. Mean age of healthy controls was 33.8 years, BMI was 23.4, and cycle length was 27.44 days. Characteristics of IVF/ICSI patients and healthy volunteers showed no statistically significant differences. Both groups predominantly consisted of nulliparous women. In IVF/ICSI patients the contraction amplitude was significantly higher compared to controls (0.062 vs 0.040; p < 0.001). The contraction power (combination of amplitude and frequency) appeared to be significantly higher in IVF/ICSI patients compared to controls (1528.18 vs 683.44; p < 0.001). No significant differences were found in contraction frequency and coordination. Even though the mean coordination did not show statistically significant differences, the values were less scattered in IVF/ICSI patients, with a much smaller range of coordination values (1.04 – 3.06) compared to healthy volunteers (1.02 – 50.33). Limitations, reasons for caution The reported difference between IVF/ICSI patients and controls in contraction amplitude and power may not solely be attributed to the administration of exogenous hormones. The difference may also be due to an underlying cause for infertility in these patients. Another limitation of this study is the small sample size. Wider implications of the findings Future research should explore which uterine contraction profile is associated with viable pregnancy: during the natural menstrual cycle, or when treated with hormones. The question arises whether it is preferred to transfer the embryo in the stimulated cycle or implement a freeze-all policy and transfer during the natural menstrual cycle. Trial registration number NCT02310802

Exogenous gonadotropin-releasing hormone counteracts the adverse effect of scrotal insulation on testicular functions in bucks

This study determined the effects of scrotal insulation on testicular functions in bucks and evaluated the impact of exogenous gonadotropin-releasing hormone (GnRH) administration before scrotal insulation on sperm production and testicular vascular dynamics. Twelve bucks were randomly divided into three groups: scrotal-insulated animals without GnRH treatment (INS), scrotal-insulated animals treated previously with GnRH (GnRH + INS), and animals without insulation as controls (CON). Doppler ultrasonography was used to evaluate testicular vascular changes, and semen samples were collected to assess seminal parameters. Testicular samples were collected from slaughtered bucks at the end of the experiment for histological investigations and immunohistochemical analysis for caspase 3 (apoptotic marker), and a vascular endothelial growth factor (VEGF; hypoxic marker) evaluation. Sperm motility drastically decreased (33%) in the INS group on day 8 compared with those in the GnRH + INS and CON groups (58% and 85%, respectively). Testicular blood flow significantly decreased for 3 and 2 weeks in the INS and GnRH + INS groups, respectively. The pulsatility index (PI) reached pretreatment values at 5 and 4 weeks after insulation in the INS and GnRH + INS groups, respectively. The resistance index (RI) values increased in both insulated groups for the first 2 weeks and decreased to control values 4 weeks after insulation. However, the maximum velocity (VP) started to increase reaching pretreatment values by the 5th and 3rd weeks after insulation in the INS and GnRH + INS groups, respectively. Histological investigations showed a marked reduction in lipid inclusions in Sertoli cells in the GnRH + INS group compared with those in the INS group. The distributions of both caspase 3 and VEGF decreased in the GnRH + INS group compared with those in the INS group. This study showed that the administration of a single dose of GnRH delayed the negative effects of scrotal insulation on different seminal traits and revealed the pivotal role of GnRH in compensating testicular insulation in bucks.

Do women’s natural hormonal fluctuations modulate prosociality? A within-subject analysis

Prosocial behavior is central to functional societies. While studies have shown that the administration of exogenous hormones modulates prosocial propensities, it remains unclear whether natural hormonal fluctuations track women’s prosocial behavior. In this study, we investigated the relationships between women’s natural salivary steroid hormone levels (estradiol, progesterone, and testosterone) and their prosociality in a variety of contexts, as measured by three behavioral tasks (Charitable Donation, Social Value Orientation, and Social Discounting tasks) and one self-reported questionnaire (the Prosocial Tendencies Measure). Participants completed five weekly laboratory tests to obtain within-subject hormonal fluctuation data and prosociality measurements. In a pre-registered analysis, we found little evidence supporting the hypotheses that women’s prosociality tracked natural changes in salivary estradiol, progesterone, estradiol-to-progesterone ratio, or testosterone. Our results demonstrate the importance of performing within-subject analyses when examining the relationships between hormonal levels and social behavior.

Hypothalamic-pituitary-adrenal (HPA) axis response to exogenous corticotropin-releasing hormone (CRH) is attenuated in men with chronic insomnia.

Although insomnia is by far the most common sleep disorder, our understanding of its neurobiology is limited. Insomnia, particularly when associated with objective sleep disturbance, has been associated with activation of the hypothalamic-pituitary-adrenal axis. The objective of this experimental study was to compare the response of the hypothalamic-pituitary-adrenal axis to ovine corticotropin-releasing hormone, a stress test, in men with insomnia versus controls. Circulating adrenocorticotropic hormone and cortisol levels were assayed before (-30min, -15min), at (0min) and after (+5min, +15min, +30min, +60min, +90min, +120min) exogenous ovine corticotropin-releasing hormone administration in 23men (11 insomnia, 12 controls), who underwent four consecutive nights of in-lab polysomnography. Men with insomnia compared with controls demonstrated markedly and significantly shorter total sleep time (368.4±8.99 min versus 411.61±8.61min; p<0.01) and lower sleep efficiency (76.77±1.80% versus 86.04±1.72%; p<0.01) on polysomnography, and showed decreased adrenocorticotropic hormone and cortisol levels after ovine corticotropin-releasing hormone administration. Adrenocorticotropic hormone levels at 15 min and 30min were significantly lower in men with insomnia than in controls (p<0.05). Similarly, the peak levels of cortisol at +60min, and the total and net area under the curve levels of this hormone were significantly lower in men with insomnia than controls (all p<0.01). Adrenocorticotropic hormone and cortisol response to ovine corticotropin-releasing hormone administration was attenuated in men with insomnia associated with objective sleep disturbance, suggesting that objectively defined insomnia subtypes have a disrupted hypothalamic-pituitary-adrenal axis function and highlight the need to develop treatments targeting the underlying hypothalamic-pituitary-adrenal axis dysregulation.

Does exogenous female sex hormone administration affect the rate of tooth movement and root resorption? A systematic review of animal studies.

BackgroundThe long-term use of contraceptive methods that contain estrogens, progestogens or combinations of the above among women aged 15 to 49 years is extensive. Both estrogens and progestogens affect bone metabolism.ObjectiveTo systematically investigate and appraise the quality of the available evidence from animal studies regarding the impact of exogenous administration of female sex hormones on the rate of orthodontic tooth movement and root resorption.Search methodsSearch without restriction in seven databases (including grey literature) and hand searching were performed until May 2021.Selection criteriaWe looked for controlled animal studies investigating the effect from exogenous administration of formulations containing female sex hormones on the rate of orthodontic tooth movement and root resorption.Data collection and analysisAfter study retrieval and selection, relevant data was extracted, and the risk of bias was assessed using the SYRCLE’s Risk of Bias Tool. The quality of available evidence was assessed with the Grades of Recommendation, Assessment, Development, and Evaluation.ResultsThree studies were identified, all being at unclear risk of bias. Overall, administration of progesterone and the combinations of estradiol with norgestrel and desogestrel were shown to significantly decrease the rate of orthodontic tooth movement when given for longer periods (>3 weeks). Inconsistent information was detected for shorter periods of consumption. Estradiol, with desogestrel use, resulted in less root resorption. The quality of the available evidence was considered to be low.ConclusionsExogenous administration of female sex hormones may decelerate in the long term the rate of tooth movement and decrease orthodontically induced root resorption in animals. Until more information becomes available, an orthodontist should be able to identify a patient consuming such substances and understand the potential clinical implications and adverse effects that may arise.RegistrationPROSPERO: CRD42017078208; https://clinicaltrials.gov/.

English

Cotton is the world's most important source of renewable fiber, and it is largely utilized in the textile industry to make clothes. In contrast to the ovule epidermis, cotton fibers are single cells that have differentiated from it, making them an attractive model system for the study of polyploidization, production of cell wall and elongation of cell. Plant hormones, that are present in very small low quantities in the plant, play essential roles in a variety of developmental processes, and new research has found that hormones play a critical role in controlling cotton fiber formation, as well as other developmental processes. For example, it has been demonstrated that the exogenous administration of hormones can stimulate the start and development of fiber cells. However, there is currently a lack of a thorough knowledge of phytohormones that regulate the formation of fiber. This paper focuses on latest developments in the understanding of the roles of different phytohormones involved in fiber development, including brassinosteroid, gibberellin, cytokinin, auxin, ethylene and abscisic acid. This paper reviews the discovery of genes associated in hormone biosynthesis and signaling pathways, as well as the methods by which these phytohormones control the commencement and elongation of fiber cells in cotton. All of the hormones involved in fiber formation are beneficial; however, cytokinin and abscisic acid are detrimental. Auxin, gibberellin, brassinosteroid, ethylene, jasmonate, and strigolactones are among the hormones involved in fiber development. A complete analysis of the function of phytohormones in cotton fiber development is our goal.

Lingual thyroid: An incidental cytological finding

Lingual thyroid (LT) is a developmental defect due to the failure of the thyroid gland to descend to its normal cervical location during embryogenesis. Lingual thyroid has an overall prevalence of 1 in 100,000 to 1in 3,00,000 and is seven to ten times more common in females than in males .Lingual position represents the most frequent ectopic location accounting up to 90% of ectopic cases. It is found at the junction of the anterior two thirds and the posterior third, between the epiglottis and the circumvallate papillae. Most cases are asymptomatic, however, increase in size can cause local symptoms like upper airway obstruction, dysphagia and hemorrhage at any time from infancy to adulthood. Thyroid scintigraphy, neck ultrasound, CT- scan, MRI are some diagnostic modalities that play a vital role in diagnosing ectopic thyroid gland. Treatment of this anomaly includes exogenous L-thyroxine hormone administration, radioiodine ablation therapy and surgery. We hereby report a rare case of lingual thyroid in a young girl reported by fine needle aspiration cytology.

Decisive evidence of direct effect of ACTH treatment in West syndrome: A case report

In patients with West syndrome, the administration of exogenous adrenocorticotropic hormone (ACTH) is considered a potent and effective treatment [1]. Exogenously administered ACTH hyperactivates the hypothalamic-pituitary-adrenal axis (Fig. 1A); however, the resulting hormonal changes cannot fully account for the therapeutic effect of ACTH. Indeed, the administration of corticosteroids to patients with West syndrome failed to provide an anti-epileptic effect comparable to that of ACTH [1]. Thus, the antiepileptic effect of ACTH in West syndrome has been postulated to involve a direct action of ACTH on the central nervous system (i.e., a “direct pathway”) that occurs independently of the hypothalamic-pituitary-adrenal axis (i.e., an “indirect pathway”).

Dynamics of lipid droplets in the endometrium and fatty acids and oxylipins in the uterine lumen, blood, and milk of lactating cows during diestrus

Our objective was to investigate the lipid content of uterus, blood plasma, and milk at early, mid, and late diestrus. Lactating cows (n = 30) had the estrous cycle and ovulation synchronized by administration of exogenous hormones. Cows were blocked by parity and assigned randomly to receive transcervical uterine flushing and biopsy on d 5 (early diestrus), 10 (mid diestrus) or 15 (late diestrus) of the estrous cycle. Flushing and endometrial biopsy were performed in the uterine horn ipsilateral to the corpus luteum. The recovered flushing was used for analyses of lipid composition by liquid chromatography-tandem mass spectrometry and the biopsy was used for investigation of lipid droplet abundance in endometrial cryosections using a neutral lipid fluorescent dye. In addition, blood and milk samples were collected from all cows on d 5, 10, and 15. All blood samples were used to measure the concentration of progesterone in plasma, and all milk samples were used to determine milk composition. Subsamples of blood plasma and milk were also used to evaluate the composition of fatty acids and oxylipins using the same methodology used for uterine flushing samples. The abundance of lipid droplets in the endometrium increased 1.9-fold from d 5 to 10, and 2-fold from d 10 to 15. Concentration of long-chain fatty acids and oxylipins in uterine flushing were, on average, 2.2 and 2.5 times greater in samples collected on d 15 compared with those collected on d 5 and 10. These differences were not observed in blood and milk, suggesting that accumulation of fatty acids and oxylipins in the uterus is regulated locally. In addition to concentration, the profile of individual fatty acids and oxylipins in uterine lumen changed substantially during diestrus. The main categories with increased abundance at late diestrus were mono- and polyunsaturated fatty acids, and oxylipins derived from arachidonic acid, dihomo-γ-linolenic acid, and docosahexaenoic acid. In conclusion, fatty acids and oxylipins accumulate in the uterine lumen during diestrus and might work as a mechanism to supply these lipids to the developing conceptus at late diestrus, when the onset of elongation occurs and substantial synthesis of biomass and cell signaling by lipid mediators are required.