Effects Of Hormones Research Articles

Abstract B015: A novel Cluster 3 Endometrial Cancer PDX model to test hormone therapy regimens

Abstract Endometrial cancer is the most commonly diagnosed gynecologic cancer and continues to rise in incidence and mortality rates worldwide. With the evaluation of large datasets including the TCGA, endometrial cancers have been subdivided into four different cluster groups based on molecular characteristics. The most common subtype of endometrial cancer is the Cluster 3 category, demarcated by the expression of estrogen receptors (ER) and progesterone receptors (PR) with the potential to respond to hormonal therapy. However, Cluster 3 tumors frequently lose hormone receptor expression over time, particularly PR, making them resistant to treatment. Although numerous cell line models exist to study this disease, there is a need for improved models to select best treatment options for the specific types of endometrial cancers. Here, we describe the development of an endometrial cancer patient derived xenograft (PDX), EC-PDX3. The initial tumor from which EC-PDX3 was derived was a low-grade endometrioid endometrial carcinoma that contained a low number of somatic copy number alterations. The tumor initially tested robustly positive for both ER and PR in the donor patient as well as in initial passages in athymic mice, making this model valuable for hormone therapy research. In these studies, EC-PDX3 cells were grown within immunodeficient NSG mice. We performed H&E, ER and PR staining prior to experimentation and found that while ER remained highly positive, PR levels were significantly downregulated, indicating the development of a hormone resistant state similar to that occurring in patients over time. To determine if these cells respond to hormonal therapy and if PR expression could be induced, mice were initially treated with estradiol to enhance PR expression. Next, mice were further treated with progesterone or onapristone, an experimental progestin agonist/antagonist with previously reported encouraging activity in advanced endometrial cancer in phase I and II trials. Tumors were measured weekly to determine hormone effects on cancer growth. Mice treated with estradiol alone showed substantially larger tumor growth as compared to the estradiol + progesterone and estradiol + onapristone treatment groups, indicating that hormone sensitivity was likely re-instated. RNA sequencing using Ishikawa cells in culture revealed the transcriptional effects of estradiol, progesterone and onapristone which complement the data obtained from EC-PDX3 bearing mice treated similarly. These studies identify interesting growth inhibitory effects of onapristone in endometrial cancer cells primed with estradiol including the significant induction of the cell cycle regulators such as p21 and genes involved in apoptosis. In addition, EC-PDX3 provides a model to assess hormonal therapy in Cluster 3 tumors that initially respond but develop resistance to treatment over time. Citation Format: Kimberly K. Leslie, Lane E. Smith, Jamie Padilla, Adrian Quintana. A novel Cluster 3 Endometrial Cancer PDX model to test hormone therapy regimens [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B015.

Role of steroid hormones in the maintenance of focal adhesions in bovine oviductal epithelial cells

The oviduct, the organ of the female reproductive system where fertilization and early embryonic development occur, provides an optimal environment for the final maturation of oocytes, storage, and sperm capacitation and transport of gametes and embryos. During the estrous cycle, the oviduct is affected by ovarian sex hormones, resulting in changes aimed at maintaining an appropriate microenvironment. Normal cell migration is tightly regulated, its role being essential for the development and maintenance of organ and tissue functions as well as for regeneration following injury. Due to their involvement in focal contact formations, focal adhesion kinase (PTK2) and paxillin (PXN) are key proteins in the study of cell migration and adhesion. The objective of this work was to compare the expression of PTK2 and PXN in oviductal cells along the estrous cycle and to determine if their expression is regulated by the presence of 17-β estradiol (E2) and/or progesterone (P4). No transcripts of PTK2 or of PXN were detected in cells corresponding to the luteal phase. Additionally, hormonal stimulation experiments on bovine oviductal cell cultures (BOECs) were carried out, where P4 inhibited the expression of both genes. Migration assays demonstrated that P4 reduced BOECs migration capacity. P4 treatment also reduced cell adhesion, while E2 increased the number of adhered cells. In conclusion, the presence of E2 and P4 regulates the expression of genes involved in the formation of focal contacts and modifies the migration and adhesion of BOECs. Understanding the effect of steroid hormones on BOECs is critical to grasp the impact of steroid control on oviductal function and its contribution to establishing successful pregnancies.

Effect of Hormones as Cofactors in Food Allergy

Effect of Hormones as Cofactors in Food Allergy

Histone modification-dependent production of peptide hormones facilitates acquisition of pluripotency during leaf-to-callus transition in Arabidopsis.

Chromatin configuration is critical for establishing tissue identity and changes substantially during tissue identity transitions. The crucial scientific and agricultural technology of in vitro tissue culture exploits callus formation from diverse tissue explants and tissue regeneration via de novo organogenesis. We investigated the dynamic changes in H3ac and H3K4me3 histone modifications during leaf-to-callus transition in Arabidopsis thaliana. We analyzed changes in the global distribution of H3ac and H3K4me3 during the leaf-to-callus transition, focusing on transcriptionally active regions in calli relative to leaf explants, defined by increased accumulation of both H3ac and H3K4me3. Peptide signaling was particularly activated during callus formation; the peptide hormones RGF3, RGF8, PIP1 and PIPL3 were upregulated, promoting callus proliferation and conferring competence for de novo shoot organogenesis. The corresponding peptide receptors were also implicated in peptide-regulated callus proliferation and regeneration capacity. The effect of peptide hormones in plant regeneration is likely at least partly conserved in crop plants. Our results indicate that chromatin-dependent regulation of peptide hormone production not only stimulates callus proliferation but also establishes pluripotency, improving the overall efficiency of two-step regeneration in plant systems.

Development of external genitalia during mini-puberty: Is it related to somatic growth or pubertal hormones?

Although hypothalamic-pituitary-gonadal axis activation and hormone levels in mini-puberty are similar to the pubertal period1, its role in human development and reproduction has not been fully elucidated2. We aimed to evaluate the effects of somatic growth and reproductive hormones on the development of external genitalia during mini-puberty

Reproductive late effects and testosterone replacement therapy in male childhood cancer survivors: A population-based study (the Fex-Can study).

Childhood cancer survivors are at risk of various endocrine late effects affecting their quality of life. The aim of this study was to assess the prevalence and predictors of endocrine and reproductive outcomes in young adult survivors. A secondary aim was to assess possible associations between testosterone replacement therapy (TRT) and other endocrine, cardiovascular and psychosocial late effects. This nationwide study comprised 1212 male childhood cancer survivors aged 19-40 years, identified through the National Quality Registry for Childhood Cancer in Sweden. Median age at diagnosis during 1981-2017 was 7 (range 0-17) and at study 29 (19-40) years. The study combined self-report survey data with cancer treatment data from the national registry. Hormone-induced puberty was self-reported by 3.8% of the survivors and ongoing TRT by 6.0%. In separate logistic regression analyses, these treatments were associated with hematopoietic stem cell transplantation and cranial radiotherapy. Hormone-induced puberty was additionally associated with younger age at diagnosis. Men with TRT had a higher prevalence of other endocrine deficiencies, cholesterol medication, depressive symptoms and fatigue as well as a lower probability of living with a partner, having a biological child or current occupation. In the total male cohort, 28.2% reported having a biological child. Reassuring reproductive outcomes after less intensive therapies and low frequency of TRT were observed in young adult male childhood cancer survivors treated in the most recent treatment era. However, men with TRT suffered from several other endocrine, cardiovascular and psychosocial late effects, indicating a need for long-term monitoring of this high-risk group.

Bioaccumulation and Potential Endocrine Disruption Risk of Legacy and Emerging Organophosphate Esters in Cetaceans from the Northern South China Sea.

Despite the increasing health risks shown by the continuous detection of organophosphate esters (OPEs) in biota in recent years, information on the occurrence and potential risks of OPEs in marine mammals remains limited. This study conducted the first investigation into the body burdens and potential risks of 10 traditional OPEs (tOPEs) and five emerging OPEs (eOPEs) in 10 cetacean species (n = 84) from the northern South China Sea (NSCS) during 2005-2021. All OPEs, except for 2-ethylhexyl diphenyl phosphate (EHDPHP), were detected in these cetaceans, indicating their widespread occurrence in the NSCS. Although the levels of the ∑10tOPEs in humpback dolphins remained stable from 2005 to 2021, the concentrations of the ∑5eOPEs showed a significant increase, suggesting a growing demand for these new-generation OPEs in South China. Dolphins in proximity to urban regions generally exhibited higher OPE concentrations than those from rural areas, mirroring the environmental trends of OPEs occurring in this area. All OPE congeners, except for EHDPHP, in humpback dolphins exhibited a maternal transfer ratio >1, indicating that the dolphin placenta may not be an efficient barrier for OPEs. The observed significant correlations between levels of OPEs and hormones (triiodothyronine, thyroxine, and testosterone) in humpback dolphins indicated that OPE exposures might have endocrine disruption effects on the dolphin population.

Effects of corticotropin-releasing hormone on gastric electrical activity and sensorimotor function in healthy volunteers: a double-blinded crossover study.

Biopsychosocial factors are associated with disorders of gut-brain interaction (DGBI) and exacerbate gastrointestinal symptoms. The mechanisms underlying pathophysiological alterations of stress remain unclear. Corticotropin-releasing hormone (CRH) is a central regulator of the hormonal stress response and has diverse impact on different organ systems. The aim of the present study was to investigate the effects of peripheral CRH infusion on meal-related gastrointestinal symptoms, gastric electrical activity, and gastric sensorimotor function in healthy volunteers (HVs). In a randomized, double-blinded, placebo-controlled, crossover study, we evaluated the effects of CRH on gastric motility and sensitivity. HVs were randomized to receive either peripheral-administered CRH (100 µg bolus + 1 µg/kg/h) or placebo (saline), followed by at least a 7-day washout period and assignment to the opposite treatment. Tests encompassed saliva samples, gastric-emptying (GE) testing, body surface gastric mapping (BSGM, Gastric Alimetry; Alimetry) to assess gastric myoelectrical activity with real-time symptom profiling, and a gastric barostat study to assess gastric sensitivity to distention and accommodation. Twenty HVs [13 women, mean age 29.2 ± 5.3 yr, body mass index (BMI) 23.3 ± 3.8 kg/m2] completed GE tests, of which 18 also underwent BSGM measurements during the GE tests. The GE half-time decreased significantly after CRH exposure (65.2 ± 17.4 vs. 78.8 ± 24.5 min, P = 0.02) with significantly increased gastric amplitude [49.7 (34.7-55.6) vs. 31.7 (25.7-51.0) µV, P < 0.01], saliva cortisol levels, and postprandial symptom severity. Eleven HVs also underwent gastric barostat studies on a separate day. However, the thresholds for discomfort during isobaric distensions, gastric compliance, and accommodation did not differ between CRH and placebo.NEW & NOTEWORTHY In healthy volunteers, peripheral corticotropin-releasing hormone (CRH) infusion accelerates gastric-emptying rate and increases postprandial gastric response, accompanied by a rise in symptoms, but does not alter gastric sensitivity or meal-induced accommodation. These findings underscore a significant link between stress and dyspeptic symptoms, with CRH playing a pivotal role in mediating these effects.

Post partum rupture of hepatocellular adenoma- a rare case report

Hepatocellular adenoma is a hormone dependent tumor of the liver. It can increase in size under the effect of hormones. It tends to increase in size under the effect of oral contraceptives (OCPs) and pregnancy. Most of the Hepatocellular Adenomas are asymptomatic and usually do not require any treatment. Hepatocellular adenoma with size &lt;5 cm carries minimal risks and complications in terms of malignant transformation and rupture. Big adenoma in advanced gestational age has a high propensity to rupture. It is a catastrophic event which requires prompt management and treatment to save life of the patient and the fetus. There are very few cases reported of rupture of hepatocellular adenoma in ante-natal phase and none in post-partum. Here in our case report, we present a case of rupture of hepatocellular adenoma in the postpartum period, which was recognized, and timely intervention was done, and we could save the life of the patient with a good prognosis.

Differential effect of estrogen and progesterone on &lt;i&gt;in vitro&lt;/i&gt; growth of uterine leiomyoma cells with chromosome 7 deletions

BACKGROUND: The studies on how sex steroid hormones affect growth of uterine leiomyoma cells with chromosomal abnormalities is highly relevant for development of personalized tumor therapy.&#x0D; AIM: To study in vitro the isolated and combined effects of estrogen and progesterone on uterine leiomyoma cells with chromosomal aberrations — deletions in 7q.&#x0D; MATERIALS AND METHODS: The study was performed on 15 uterine leiomyomas, excised from 15 women of 26–44 years of age who were not treated with hormones. Uterine leiomyoma cells were cultured in hormone-free medium, in the medium supplemented with estrogen, progesterone or both hormones. The chromosome preparations were made and stained with QFH/AcD to perform conventional karyotyping and fluorescence in situ hybridization (FISH) to accurately describe chromosomal rearrangements. The frequency of uterine leiomyoma cells with chromosomal aberrations was assessed by interphase FISH.&#x0D; RESULTS: Deletions in 7q were identified in 6 out of 15 karyotyped uterine leiomyomas; four of them had one clone with deletion in 7q whereas two others comprised two clones with 7q deletions of different length. The frequency of cells carrying deletions in 7q greatly varied in uterine leiomyoma samples cultured in hormone-free medium: from 3.5% to 93.6%. Exposure of cell cultures to estrogen and progesterone resulted in a fold change frequency increase in some of the uterine leiomyomas and decrease in the others. The most significant changes in the frequency of cells with deletions in 7q were registered in response to the isolated estrogen and, to a lesser extent, to progesterone exposure; less significant changes were observed after combined hormonal effect.&#x0D; CONCLUSIONS: In uterine leiomyomas with deletions in 7q, the frequency of abnormal cells may either increase or decrease in response to estrogen and progesterone in vitro supplementation. The isolated effect of estrogen or progesterone on the frequency of uterine leiomyoma cells with deletion in 7q is more pronounced compared to the combined one.

POSTN promotes granulosa cell proliferation in sheep follicles through focal adhesion

BackgroundThe complex regulatory mechanisms involved in follicular development in sheep are not fully understood. This study aimed to understand the expression of periostin (POSTN) in granulosa cells (GCs) and its effect on follicle development. MethodsThe effect of luteinizing hormone (LH) treatment on POSTN expression in GCs was examined. POSTN was overexpressed or inhibited in GCs, and its effects on cell proliferation and apoptosis, as well as potential mechanisms of action, were evaluated. ResultsPOSTN showed higher expression in ovarian tissue than in other tissues and higher expression in large follicles than in small follicles. LH treated GCs promoted POSTN expression. Overexpression of POSTN in GCs significantly increased cell proliferation and inhibited apoptosis. Phosphorylation levels of focal adhesion kinase and autophagy were elevated in POSTN overexpressing GCs. ConclusionPOSTN affects GCs proliferation and follicle development through the focal adhesion, potentially improving fecundity in sheep.

Associations between thyroid hormones and appendicular skeletal muscle index, and hand grip strength in people with diabetes: The KAMOGAWA-A study

AimTo assess the effects of thyroid hormones on appendicular skeletal muscle index (SMI) and hand grip strength (HGS) in people with diabetes. MethodsThis cross-sectional cohort included 1,135 participants with diabetes admitted to 3 hospitals in Japan. Multiple regression analysis was performed to determine the associations among thyroid hormone levels, SMI, and HGS. ResultsOf the 1,135 participants, 480 were female. Their median (interquartile range) age, body mass index, durations of diabetes, and glycated haemoglobin levels were 68 years, 24.3 kg/m2, 10 years, and 7.6 %, respectively. The median (interquartile range) SMI (kg/m2) and hand grip strength of the cohort were 7.1 kg/m2 and 28.2 kg, respectively. Positive correlations between FT3 and the FT3/FT4 ratio with SMI and HGS was observed after adjusting for covariates in males. A negative correlation was found between the FT3/FT4 ratio and sarcopenia as a result of low SMI and low HGS in the male participants but not in females (p for interaction = 0.02). ConclusionsFT3/FT4 ratios may impact skeletal muscles in people with diabetes—particularly in males. Assessments of FT3/FT4 ratios may represent key indicators of muscle mass and strength in males.

Opposing effects of thyroid hormones on hypothalamic subunits and limbic structures in hyperthyroidism patients: A comprehensive volumetric study.

Thyroid hormones play a critical role in brain development, but paradoxically, patients with hyperthyroidism often exhibit cognitive decline and irritability. This study aims to explore the pattern of atrophy in hyperthyroid patients, changes in specific areas of the brain, including hypothalamic subfields and limbic structures, and their relationships with hormonal levels and psychometric tests. This prospective cross-sectional study involves 19 newly diagnosed, untreated hyperthyroid patients, and 15 age and gender-matched control subjects. The participants underwent psychometric and cognitive tests and volumetric MRI. The hypothalamic subfield (anterior-inferior, anterior-superior, superior-tubular, inferior-tubular, and posterior hypothalamus) and limbic structures (fornix, basal forebrain, nucleus accumbens, and septal nucleus) were segmented using voxel-based morphometry, surface-based morphometry, and deep learning algorithms. The groups were compared using the t-test, and correlation analyses were performed between clinical parameters and volumetric measurements. The correlation between hormonal parameters and volumetric measurements in patient and control groups was assessed with the Meng test. Hyperthyroid patients displayed widespread grey matter loss and sulcal shallowing in the left hemisphere. However, no local gyrification index changes or cortical thickness variations were detected. The limbic structures and hypothalamic subunits did not show any volume discrepancies. Free thyroxine in the patient group negatively correlated with bilateral anterior-inferior and right septal nucleus, but positively correlated with left anterior-inferior in the control group. Thyroid stimulating hormone in the patient group showed a positive correlation with bilateral fornix volume, a correlation absent in the control group. Disease duration negatively correlated with right anterior-inferior, right tubular inferior, and right septal nucleus. Changes in cognitive and psychometric test scores in the patient group correlated with the bilateral septal nucleus volume. Hyperthyroidism primarily leads to a reduction in grey matter volume and sulcal shallowing. Thyroid hormones have differing volumetric effects in limbic structures and hypothalamic subunits under physiological and hyperthyroid conditions.

(264) Prioritizing Sexual and Reproductive Health Research and Care for People with Cystic Fibrosis: A 2023 Workshop Report From the Cystic Fibrosis Foundation Sexual Health, Reproduction, and Gender Research (SHARING) Working Group

Abstract Introduction With therapy advances, people with cystic fibrosis (CF) are living longer, healthier lives, and thus increasingly have general and CF-specific sexual and reproductive health (SRH) questions. The CF Foundation is supporting the Sexual Health, Reproduction, and Gender Research (SHARING) Working Group to identify knowledge gaps, research priorities, and infrastructure needed for CF SRH research. SHARING includes pulmonologists, nurses, research coordinators, registered dieticians, psychiatrists, endocrinologists, reproductive urologists, and community members with CF. Objective In Spring 2023, SHARING developed and distributed a SRH prioritization survey for the CF community. During the annual in-person workshop, the group used these results to establish research priorities and develop studies that would address identified knowledge gaps. Methods SHARING partnered with Community Voice, a virtual platform for people with CF and their caregivers to share their perspectives on ongoing and future CF SRH research, care, and programming. We provided a list of 15 SRH research topics and asked respondents to rank the top five. We analyzed survey results using descriptive statistics. We also summarized discussions and future key directions for CF SRH research. Results A total of 303 respondents (85% people with CF and 15% caregivers) completed the survey. Sixty-five percent of people with CF were women and 37% of the people with CF for whom caregivers responded were women/girls. The majority (95% of adults, 98% of people with CF for whom caregivers responded) identified as White; 5% of adults and 10% of people with CF for whom caregivers responded were Hispanic/Latino. The majority (73%) of people with CF were &amp;gt;30 years old and 68% of those with CF for whom caregivers responded were &amp;lt;18 years old. Table 1 summarizes respondent demographics. The top five SRH topics were: 1) effects of CF modulator therapy (elexacaftor/tezacaftor/ivacaftor, ETI) on sex hormones; 2) effects of sex hormones on CF; 3) fertility; 4) pregnancy; and 5) SRH/mental health (Figure 1). People with CF prioritized pregnancy, sexual functioning, parenthood, and menopause, while caregivers prioritized ETI effects on sex hormones, fertility, mental health, and assisted reproductive technology (ART). SRH priorities differed by gender identity. Men and caregivers of men/boys prioritized fertility, mental health, SRH care provision, sexual functioning, and ART, while women and caregivers of women/girls prioritized the effect of sex hormones in CF, pregnancy, menopause, and contraception. During workshop proceedings, SHARING identified the need for further research on the interplay between sex hormones, CF pathophysiology, ETI, fertility, and ART, and a focus on the impact of infertility on mental health for males with CF. Conclusions SRH is an important and emerging area of research in CF. Research priorities are not uniform among people with CF and their caregivers, particularly across genders. Thoughtful consideration of such perspectives can ensure that future CF SRH research is relevant and responsive to CF community needs. SRH providers should be aware of the concerns in this understudied population from research and patient care perspectives. Disclosure No.

(157) Prescribing Ozempic and Wegovy for Weight Loss is Associated with an Increased Risk of Erectile Dysfunction and Hypogonadism in Non-Diabetic Males

Abstract Introduction The use of antidiabetic medications, such as metformin or sulfonylureas, can have diverse effects on sex hormones, potentially influencing erectile function. While both Ozempic and Wegovy (semaglutide) include sexual dysfunction as a side effect of the medication, no study has assessed how frequently men will experience sexual dysfunction with these medications. Recently, semaglutide was approved in June of 2021 for weight loss in non-diabetic patients and has exploded in popularity. Objective Our objective is to assess the risk of developing ED in non-diabetic males after starting semaglutide using a large claims-based database. Methods We queried the TriNetX Research database, a comprehensive insurance claims database. Our study cohort included males aged 18 to 50 who have been prescribed semaglutide after June 1st, 2021. We excluded individuals with a history of pelvic radiation, prostatectomy, pulmonary hypertension, diabetes mellitus, or any hemoglobin A1c measurement ≥7%. Propensity-matching was performed between the cohorts for age, ethnicity, race, BMI, hypertension, sleep apnea, and hyperlipidemia. Our primary outcome was comparing the proportion of men that received an ED diagnosis and/or prescription for phosphodiesterase-5 inhibitors (PDE5i) from one day to any time after the index prescription of semaglutide. The secondary outcome of interest included the risk of developing testosterone deficiency. Risk was reported using relative risk (RR) with 95% confidence intervals (CI). Statistical significance was set using a two-sided alpha at 0.05. Results We found 2,117 non-diabetic males with a prescription of semaglutide, which were compared to an equivalent number of propensity matched controls (Table 1). Compared to matched controls, males with a semaglutide prescription were significantly more likely to be diagnosed with ED and/or prescribed PDE5i (1.4%) when compared to control males who were never prescribed semaglutide (0.14%) (RR: 10.0, 95% CI [3.05 – 32.82]). Similarly, males with a prescription for semaglutide were more likely to receive a subsequent diagnose of testosterone deficiency (3.83%) compared to controls (1.7%), (RR: 2.25, 95% CI [1.53 – 3.32]) from one day to any time after the index prescription. Conclusions In this claims-based analysis, we found that non-diabetic males with a prescription of semaglutide have a significantly higher risk of developing ED and testosterone deficiency. Rates of erectile dysfunction in men prescribed semaglutide are overall low at 1.4% but, we were surprised that these rates were so much higher than those not receiving semaglutide as we expected that weight loss drugs would improve erectile function. Further studies are needed to assess the impact of semaglutide in non-diabetic men to assess how this drug impacts the male hypothalamic-pituitary-gonadal axis. Despite its increasing popularity for weight loss, both clinicians and patients should be aware of potential hormonal effects when discussing and considering the medication. Disclosure No.

Morphometric analysis of orbital CT scan in a Jordanian sample

ABSTRACT Background Anatomical variation exists among different ethnicities in almost all body parts, including the bony skull. Researchers have found some variations between both sexes in the inner measurements of the bony orbit as well as variations related to racial differences. In this study, we assessed different parameters related to the bony orbit that are important clinically, using data collected from a random sample of the diverse population of Jordan, seeking to find out how our population correlates with the variations mentioned in the literature, and applying the results for their clinical importance for many disciplines of medicine related to ophthalmology and maxillofacial surgery, among others. Research Design and Methods This was a cross-sectional study conducted on healthy patients from the Jordan University Hospital. We randomly selected participants aged between 17 and 89, who attended the ophthalmology clinic in the Jordan University Hospital. For each patient, we obtained clinical data and computed tomography (CT) images, using four two-dimensional measurements of the orbit: D1 = distance from the orbital canal to the frontozygomatic fissure, D2 = distance from the orbital canal to the nasion, D3 = distance between the supraorbital and infraorbital canals, and D4 = distance between the nasion and the frontozygomatic fissure. Results We included a total of 161 participants, with a mean age of 54.4 (±19.3) years. They were 83 men (51.6%) and 78 women (48.4%). We found a significant difference in D3 between Jordanian males and females from various races, which might indicate a possible strong effect of sexual hormones on the orbital development. Conclusions We analyzed different measurements that are clinically relevant on a sample of Jordanian patients. These measurements can be useful for surgical decision-making and for research purposes. Our key limitations were related to concerns about the safety of CT imaging for the soft tissue of the eye and the use of two-dimensional measurements instead of three-dimensional ones.

Effects of Auxin and Gibberellins Hormones on Regeneration of Pineapple Propagules from Crown Leaves (with Buds) in Kilifi County Kenya

Kilifi county has a large potential of over 2,000 Ha suitable for pineapple cultivation that has not been fully exploited due to lack of adequate clean planting material. Thus, the aim of the study was to evaluate the effects of auxin and gibberellin hormones on regeneration of pineapple propagules from pineapple crown leaves (with buds). The study was carried out at Pwani University Crop Science farm. A randomized complete block design with split plot arrangement replicated thrice was used. Treatments included auxin and gibberellins hormones where the cut crown leaves (with buds) were dipped and planted at a spacing of 4 cm by 6 cm in plastic containers filled with coir dust. Five plastic containers were used for each hormone treatment. In each container, three plants were tagged for data collection. The plastic containers (the plots) measured 30cm by 36cm by 15cm height. Data collected from the tagged plants included, time to shoot emergence, plant height, leaf length and breadth, number of leaves per plant, final root length and final number of roots. These were used to determine effects of auxin, gibberellins on growth of the propagules up to a height of 15-20 cm. Obtained data was subjected to ANOVA analysis using Genstat Statistical software 14th Edition and means obtained compared using Tukey’s honest significant difference test (p &lt; 0.05). The results indicated auxin treated propagules had 50.7%, 50.6%, 64.2%, 52.6%, 24.4%, 10.4%, 39.0%, and 9.9% higher final values of plant weight, shoot weight, dry shoot weight, fresh root weight, plant height, leaf number, root number, dry root weight and root length, respectively, compared to those treated with gibberellins. The study also showed that auxin treated propagules had their initial roots originating from the base of the seedlings, while gibberellins treated propagules had their initial roots originating from the base of the cut crown leaves.

Potential therapeutic efficacy of photodynamic therapy on female hormonal-dependent cancers in a hormonal simulated microenvironment

BackgroundPhotodynamic Therapy (PDT) is a clinically approved cancer treatment. Sex hormones, the key drivers for the development of female hormonal dependent cancers, might affect cancer treatment. There are seldom studies to evaluate the effect of sex hormones mimicked the menstrual cycle on the PDT mediated by prodrug 5-aminolevulinic acid (ALA) and its ester derivatives to the hormonal dependent cancers. AimsTo evaluate the efficacy of sex hormones on Hexyl-ALA-PDT in hormonal dependent cancers and the effect of the sex hormones on heme biosynthetic pathway. MethodsCell culture system that mimicked the fluctuation of sex hormones 17β-estradiol (E2) and progesterone (PG) in the menstrual cycle was developed. Two pairs of hormonal-independent and hormonal dependent uterine sarcoma and breast cancer cell lines were used as cell models. Hexyl-ALA induced PpIX production and intracellular localization were examined. Key enzymes for PpIX synthesis were analysed. Hexyl-ALA-PDT mediated phototoxicity was evaluated. ResultsThe PpIX generation was increased in the hormonal-dependent cells (28–50 %) when cultured in the hormonal microenvironment with long incubation of Hexyl-ALA for 15 and 24 h compared to that cultured without hormones; whereas only slight difference in PpIX generation in their hormonal-independent counterpart. The PpIX generation was in a time-dependent manner. The CPOX, PPOX and FECH expressions were significantly enhanced by Hexyl-ALA-PDT in uterine sarcoma cells in hormonal microenvironment. Hexyl-ALA-PDT triggered significant increase of PPOX expression in breast cancer cells in hormonal microenvironment. The Hexyl-ALA-PDT phototoxicity was enhanced by 18–40 % in cells cultured in the hormonal system in a dose-dependent manner. ConclusionThe PpIX generation and the efficacy of Hexyl-ALA-PDT in both uterine sarcoma and breast cancer cells was significantly enhanced by the sex hormones via cultured in the hormonal microenvironment.

Abstract A043: Building a mammary-specific microenvironment for investigating sex hormones in microvessels and tumors

Abstract The mammary gland is highly vascularized and is exposed to alterations in sex hormones, including estrogen (E2) and progesterone (P4), which also play a role in breast cancer development and progression. Yet, our understanding of hormonal changes on the microvasculature in mammary tissue is limited to studies in rodents and simple 2D cultures. Advances in organ-on-chip technology now allow for models of 3D human microvessels to be generated. However, most microvascular models lack tissue-specific cell types, limiting their physiologic relevance. Thus, we first aimed to generate a tissue-specific breast microvasculature, and next used this model to study the impact of sex hormones. Our final goal is to generate a combined vascularized model of luminal A tumor on-chip. In our recently archived work (doi: 10.1101/2023.04.21.537664), we achieved the first in vitro perfusable breast-specific microvessels. Optimal conditions were achieved to co-culture human mammary vascular endothelial cells HMVEC and mammary fibroblasts on-chip. Through image-based quantification, microvessel morphology, not barrier function, was shown to be strongly influenced by the abundance of fibroblasts, which were critical to achieve lumenized (patent) vessels. Attaining perfusable microvessels allowed the study of discreet phases of the menstrual cycle (period, follicular, ovular, and luteal). The most striking results were observed with high concentrations of E2 (mimic of ovulation phase), which presented with increased vascular growth, and in contrast with high concentrations of P4 (mimic of luteal phase) that resulted in vascular rarefaction (pruning). Effects from combined E2 and P4 were dose-dependent, as demonstrated by significant branching and remodeling in the follicular phase. Hormonal effects were also tissue-specific, as shown by HUVEC-derived microvessels with significantly different morphologic phenotypes in comparison to HMVEC. Interestingly, fibroblasts expressed significantly high levels of receptors for both hormones and likely are major contributors to the hormone-responsiveness of microvessels. With mammary vessels now established, model tumors, spheroids, were generated from luminal-like breast cancer cells. Namely, MCF-7 and T47D, were treated by the same E2 and P4 conditions as in the microvessels. For both tumor spheroids, phase-dependent responses were observed, with high E2 resulting in the most significant growth. Ongoing work has shown the capacity to incorporate these tumor spheroids into our microvascular model, which results in varied local changes in vascular density. Future work involves investigating the role of hormones in the combined tumor-microvascular model. This complex humanized model will be useful in highlighting potential cancer treatment timelines (relevant to female menstrual cycle) and may be used to uncover novel therapeutic targets for luminal A breast cancers. Citation Format: Carmen Moccia, Marta Cherubini, Guido Frigieri, Kristina Haase. Building a mammary-specific microenvironment for investigating sex hormones in microvessels and tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A043.

Unveiling the Influence of the Menstrual Cycle on Mental Rotation Abilities: A Comparative Analysis of Three-Dimensional vs. Two-Dimensional Tasks

The activational effects of sex hormones on spatial ability have been well documented. It has been suggested that these effects might be related to hormonally induced changes in interhemispheric communication. In this EEG study, we opted to explore menstrual cycle-related changes in the efficacy of solving mental rotation tasks and laterality indices while participants were engaged with the tasks. We compared 2D and 3D mental rotation tasks, as they differ both psychometrically and in terms of lateralization. A group (n = 39) of healthy young women was tested twice, once during the mid-luteal (high estrogen and progesterone) and once during the early follicular (low levels of sex hormones) phase of menstrual cycle. The differences in power within the same frequency band on homologous sites of the left and right hemispheres were then calculated. Participants were faster, more accurate, and showed higher laterality scores when solving 3D mental rotation tasks in the early follicular phase compared to the mid-luteal phase. This indicates a higher lateralization of this specific spatial function when the levels of sex hormones are low. However, for 2D mental rotation tasks, participants showed neither shifts in efficacy nor in hemispheric laterality as a function of the menstrual cycle. This pattern of results provides further support for the notion that fluctuations in sex hormones affect laterality, and consequently, the expression of lateralized cognitive abilities.