bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT425 Effects Of Endocrine-disrupting Polychlorinated Biphenyls On Adolescent Microglial Cytokine Expression And Responses To Secondary Inflammatory Challenge
Authors: Kissinger Shawn L , Fitzgibbon Addison J , Mejia Rafael A , Bell Margaret R 
Published: October 2023

Abstract
Disclosure: S.L. Kissinger: None. A.J. Fitzgibbon: None. R.A. Mejia: None. M.R. Bell: None.
Polychlorinated biphenyls (PCBs) are a group of ubiquitous environmental endocrine-disrupting chemicals (EDCs), and exposure is associated with endocrine, neuronal, and immune dysfunction in various tissue types. Innate immune cells of the nervous system called microglia are critical in responding to infection and injury, and disruption of these functions is associated with neurodegenerative disease and mental health disorders. In addition, microglia are known to regulate developmental processes during neonatal and adolescent periods, in hormone-sensitive and age- and sex-differentiated ways. Work in our lab has shown that early life PCBs can affect microglia function in ways that depend on the age and sex of the individual rat in vivo. Ongoing work uses in vitro approaches to demonstrate direct effects on microglia. In primary culture, preliminary data suggest that acute PCB exposure causes neonatal microglia to become hyperresponsive to a secondary challenge; however, effects in adolescent microglia are unknown. To test the hypothesis that PCB exposure directly alters microglia activity in an age- and sex-specific manner, we determined the effects of PCBs on cytokine gene expression in acutely isolated microglia, with or without a secondary lipopolysaccharide (LPS) challenge. Adolescent Sprague-Dawley rats underwent transcardial saline perfusion, brains were removed and homogenized into a single cell suspension with collagenase and mechanical disruption, and debris was removed. Microglia, identified as CD11b+ cells, were collected by magnetic bead isolation and plated in enriched media for 24 hours prior to experimentation. Cells were exposed to one of three concentrations of PCB 153 (0.1 µM, 1 µM, 10 µM), DMSO vehicle, or DMEM/F12 media control for 18 hours, followed by a 4-hour LPS challenge (0.5 µg/mL) or PBS vehicle control. RNA was isolated and converted to cDNA for qPCR analysis of Tnf and Il1b gene expression, analyzed by two-way (exposure x challenge) ANOVAs within both male and female cells. Results indicate that 1.0 µM PCB 153 exposure caused an increase in expression of both cytokines, more so in females than males. Preliminary results (n = 3) indicate that the 10 µM dose may also blunt the later LPS response. These results confirm that microglia are directly sensitive to PCBs, however they illustrate that cells may show differential responses depending on the stage of development. Continued work will explore acute cell toxicity and confirm release of cytokines. Adolescent microglia dysfunction from PCB exposure may be a mechanism of adolescent-onset disorders, or increased risk of neurodegenerative conditions triggered by additional challenges later in life.
Presentation: Saturday, June 17, 2023
SAT426 Long-term Nanomolar Bisphenol A (BPA) Exposure of MCF7 Cells Induces DNA Methylation Changes
Authors: Dela Cruz Sam Ezrael L , Velarde Michael C , Bagamasbad Pia D 
Published: October 2023

Abstract
Disclosure: S.L. Dela Cruz: None. M.C. Velarde: None. P.D. Bagamasbad: None.
Breast cancer (BCa) has the highest worldwide prevalence and mortality rate among cancers. For ER-positive luminal BCa, hormone deprivation therapy using drugs that inhibit the estrogen signaling axis is commonly employed. However, activation of ER may persist due to the presence of endocrine disrupting chemicals (EDCs) that are structurally similar to endogenous estrogens. Bisphenol A (BPA) is a known EDC found in consumer products and has been associated with increased BCa risk in various animal models. Mechanistically, BPA weakly binds and activates ER resulting in transcriptional changes. In addition, studies show that BPA potentially reprograms the epigenome through changes in DNA methylation. While methylome studies on BPA-exposed cancer models have been conducted, to the best of our knowledge, this has not been done on luminal BCa cells chronically exposed to environmentally relevant doses of BPA. The use of a chronic, nanomolar-dose treatment paradigm is significant as it more accurately reflects non-occupational environmental exposure. In this study, we investigated the epigenetic effects of chronic (8 weeks) nanomolar doses (10 nM) of BPA on the ER-positive BCa cell line MCF7. We probed single gene-level DNA methylation through Bisulfite Sequencing PCR (BSP) and genome-wide methylation through Reduced Representation Bisulfite PCR (RRBS). In silico analysis of publicly available data identified potential differentially methylated regions (DMRs) upon chronic BPA treatment. BSP showed minimal changes in methylation levels of CpGs within the target DMRs, while gene expression analysis via RT-qPCR did not find significant changes in mRNA levels of genes encompassing the target regions. Methylome-wide profiling of chronically treated cells identified DMRs that fall under gene promoters (DMPs) and gene coding regions (DMGs). Pathway analysis of DMPs indicated an association with death receptor signaling, with an overall predicted effect in inhibiting apoptosis. Network analysis revealed genes encompassing DMPs that interact with the BCa markers ESR1/2, BRCA1, and PGR. Based on the pathway and network analyses, we selected 8 genes for gene expression analysis and found that the expression of all 8 genes are unchanged following chronic BPA treatment. Taken together, our results show that chronic BPA exposure of MCF7 can induce subtle changes in DNA methylation. Although initial validation did not reveal changes in gene expression associated with differential methylation, we speculate that the incremental DNA methylation changes could accumulate over time resulting in further ER signaling dysregulation, exacerbating the BCa phenotype.
Presentation: Saturday, June 17, 2023
SAT429 Progesterone Secretion And The Estrous Cycle In The Mouse Are Disrupted By Mitochondrial Fusion Promoter M1 Injection During Proestrus
Authors: Budi Yovita Permata , Hsu Meng-Chieh , Lin Yi-Chun , Lee Yue-Jia , Chiu Hsin-Yi , Chiu Chih-Hsien , Jiang Yi-Fan 
Published: October 2023

Abstract
Disclosure: Y.P. Budi: None. M. Hsu: None. Y. Lin: None. Y. Lee: None. H. Chiu: None. C. Chiu: None. Y. Jiang: None.
In the female reproductive system, mitochondria play a crucial role in steroid hormone synthesis. Literature reports on changes in mitochondrial dynamics throughout the ovarian cycle, but its role in the ovarian cycle is still unknown. In this study, a mitochondrial fusion promotor, M1, was used to study the impact of mitochondrial dynamics in the female reproductive system. The estrus cycle of mice was monitored before, during, and after the M1 treatment to test the impact of M1 on ovarian functions. Our results showed that M1 treatment in mice leads to the disruptions of estrous cycles in vagina smears. To observe the acute effects of M1, serum hormones level was observed, and the decrease in serum LH and progesterone was recorded in the animal. Similarly, our ovarian tissue culture also indicates inhibitions of progesterone secretion and ovulations. Although no significant changes in mitochondrial networks were observed in the ovaries, there was significant up-regulation of mitochondrial respiratory complexes in M1 treatments through transcriptomic analysis. In contrast to the estrogen and steroid biosynthesis up-regulated in M1, the extracellular matrix molecules, remodeling enzymes, and adhesion signaling decreased. Collectively, our study provides novel targets to regulate the ovarian cycles through the mitochondria. However, more studies are still necessary to provide the functional connections between mitochondria and the female reproductive system.
Presentation: Saturday, June 17, 2023
SAT430 Effect Of Organochlorine Pesticides On Brown Adipose Thermogenesis
Authors: Huang Shenq-Shyang , Jugan Juliann Amela , Harrigan Jenna , Singla Aman , Huang Victoria , Mann Chanapa Michelle , La Merrill Michele 
Published: October 2023

Abstract
Disclosure: S. Huang: None. J.A. Jugan: None. J. Harrigan: None. A. Singla: None. V. Huang: None. C.M. Mann: None. M. La Merrill: None.
Mammalian non-shivering thermogenesis is canonically controlled by β-adrenergic signaling in brown adipose tissue. The β-adrenergic receptors Adrb1, Adrb2, and Adrb3 receive the signals from upstream sympathetic neurons, activate adenylyl cyclase, and increase the expression of uncoupled protein-1 (UCP1) which dissipates energy to produce heat. The banned but persistent pesticide dichlorodiphenyltrichloroethane (DDT) along with its metabolite, dichlorodiphenyldichloroethylene (DDE), jointly referred to as DDX, are consistently associated with increased risk of present-day obesity and type II diabetes. In addition, DDX reduced body temperature by reducing sympathetic axons innervation in mice. However, the effect of DDX on the expression of β-adrenergic receptors and thermogenesis in brown adipocytes and other mammals is unclear. Therefore, the association between DDX exposure and the expression of β-adrenergic receptors and thermogenesis in vitro and in vivo was investigated. To this aim, Sprague-Dawley (SD) rats were fed high-fat diet and gavage of either a very low dose DDX mixture (5.6μg/kg weekly for 4 weeks) or olive oil vehicle control. DDX caused a significant reduction in body temperature after two weeks without significant changes in caloric intake or food efficiency. Notably, among all the β-adrenergic receptors, only Adrb3, and Ucp1 were downregulated in the brown adipose of DDX-treated rats. These results suggest that DDX reduces body temperature by attenuating Adrb3 expression in rat brown adipose tissue. To test whether this could explain the previously observed risk of human obesity associated with DDX exposure, we used immortalized human brown adipocytes to evaluate the effect of DDX on the RNA expression of β-adrenergic receptors, UCP1, and thermogenic function. As observed in rat brown adipose, DDT and DDE each reduced the expression of ADRB3 and UCP1, but not ADRB1 or ADRB2 in immortalized human brown adipocytes. Further, DDT and DDE each decreased heat produced by the human brown adipocytes. In addition, the reduced expression of UCP1 in DDX-treated human brown adipocytes was dependent on the presence of adenylyl cyclase (AC) activator, forskolin, demonstrating that the expression of UCP1 can be rescued by bypassing the upstream β3-adrenergic receptor. In conclusion, this evidence supports the hypothesis that obesogenic pesticides, DDT and DDE, attenuate thermogenesis by impairing brown adipocyte expression of the β3-adrenergic receptor and UCP1 in several mammalian species.
Presentation: Saturday, June 17, 2023
SAT437 Immunotherapy Induced Pituitary Apoplexy
Authors: Uddin Ashraf , Gardner Michael J , Akofu Anota , Sheung Nicole , Dejhansathit Siroj , Akabogu Nwamaka , Marium Fnu 
Published: October 2023

Abstract
Disclosure: A. Uddin: None. M.J. Gardner: None. A. Akofu: None. N. Sheung: None. S. Dejhansathit: None. N. Akabogu: None. F. Marium: None.
We present a case of a 42 year old male with past history of metastatic melanoma s/p 3 cycles of ipilimumab and nivolumab immunotherapy that originally was referred to endocrinology due to elevated prolactin of 40 and MRI finding of questionable 6 mm pituitary adenoma. There was not a clear other cause of prolactin elevation. Other notable labs in pituitary hormonal evaluation were elevated FSH of 24 and LH 16 with normal testosterone 663. TSH of 4.3 and FT4 of 1.22. After the 4th cycle of ipilimumab and nivolumab he had a severe headache that was unremitting, he called his oncology nurse line which instructed him to hydrate. He presented for admission to the hospital after coming confused, unsteady on his feet and his headache had already improved. Labs demonstrated severe hyponatremia at 111 with serum osm of 238 and urine osmolality of 504 and specific gravity of 1.012. Brain MRI demonstrated a 1.2 cm pituitary lesion compared to less than 1 month prior, consistent with hypophysitis. Repeat pituitary labs showed hypogonadotropic hypogonadism with total testosterone of 39 and inappropriately normal FSH of 7 and LH of 2, central hypothyroidism with TSH 0.232, FT4 0.70, FT3 1.8, secondary adrenal insufficiency with cosyntropin stimulation test up to cortisol of 16 for partial response and ACTH of 17. Hyponatremia was managed inpatient and he was discharged on appropriate hormone replacement. Subsequent brain MRI with normal pituitary finding without enhancing lesions. Repeat hormonal testing showed persistent hormonal deficiencies with undetectable cortisol and ACTH despite holding hydrocortisone therapies. Prolactin was also tested in the 4-10 range on repeat testing. He continued on nivolumab monotherapy with oncology.
This case report details a clear case of immunotherapy treatment leading to destruction of prolactinoma and presentation of pituitary apoplexy given the short time line of 1 month and cycle of therapy between radiographic and hormonal assessment. We hope this case helps bring awareness to the evolving list of conditions to survey for with immunotherapy and suggests a role of identifying prolactinomas biochemically and or radiographically to affect management. It may even suggest a role in treatment for medically refractory pituitary adenomas.
Presentation: Saturday, June 17, 2023
SAT640 Maternal Preconception Exposure Leads To The Propagation Of Disease
Authors: Davis Daniel Dewitt , Chamorro-Garcia Raquel , Diaz-Castillo Carlos 
Published: October 2023

Abstract
Disclosure: D.D. Davis: None. R. Chamorro-Garcia: None. C. Diaz-Castillo: None.
Tobacco products harbor a heterogeneous cluster of endocrine-disrupting chemicals (EDCs) that can lead to many adverse health effects, including obesity and other metabolic diseases. During critical developmental windows, exposure to EDCs found in tobacco products, including inorganic arsenic (iAs) and nicotine, can increase susceptibility to these diseases. An understudied window of significant influence on the susceptibility to developing adverse health effects in future generations is during maternal preconception (i.e., maternal preconception exposure, MPE). MPE involves essential processes of maternal germline development, such as oogenesis and folliculogenesis. Oogenesis begins at birth with an oogonium and goes through a maturation process that either ends after ovulation as a secondary oocyte or, if fertilized, becomes a zygote. Concurrently, folliculogenesis occurs and is the process by which the oocyte develops within the ovarian follicle into a mature egg. This ovarian follicle consists of many somatic cells that contribute to the maturation of the oocyte via paracrine mechanisms. We found that female offspring of mothers exposed to 200 µg/mL nicotine and male offspring exposed to both nicotine and a combination of 10 µg/L iAs + 200 µg/mL nicotine during MPE had higher weights during early development. Females whose mothers were exposed to 10 µg/L iAs showed an insulin resistance phenotype after intraperitoneal injection of insulin. Interestingly in males from mothers that were exposed to 10 µg/L iAs and 200 µg/mL nicotine we found impaired glucose tolerance after intraperitoneal injection of glucose. These data support the hypothesis that MPE is a critical window of susceptibility to metabolically associated diseases later in life. Future directions involve expanding the previously stated experiment by performing in vitro fertilization and embryonic implantation in mothers not exposed to our chemical treatment. The goal of this will be to investigate if the offsprings have similar health outcomes to the mice born of natural fertilization, which, if they do, would indicate the alterations were occurring before fertilization. We also aim to determine the mechanisms that trigger the phenotypes observed in the F1. We will analyze alterations of the somatic cells of the antral follicle and oocyte before ovulation by performing transcriptomic analyses.
Presentation: Saturday, June 17, 2023
THU009 Subclinical Cushing’s Syndrome In An ACTH-secreting Pituitary Macroadenoma
Authors: Akabogu Nwamaka Gloria , Kumar Deepak , Sheung Nicole , Akofu Anota , Uddin Ashraf , Dejhansathit Siroj , Marium Fnu , Goonetilleke Kurukulasuriya Lilamani Romayne 
Published: October 2023

Abstract
Disclosure: N.G. Akabogu: None. D. Kumar: None. N. Sheung: None. A. Akofu: None. A. Uddin: None. S. Dejhansathit: None. F. Marium: None. L.G. Kurukulasuriya: None.
Background: Subclinical Cushing’s syndrome (SCS) is characterized by subtle cortisol hypersecretion, which does not result in the typical signs and symptoms of Cushing’s syndrome (CS). While many of the signs and symptoms of CS are common in the general population, there are some that are discriminatory and specific for CS: supraclavicular fat pads, proximal muscle weakness, facial plethora, and violaceous striae. SCS manifests mostly as obesity, type 2 diabetes, and hypertension. Diagnosing SCS is challenging; however, the best screening test to uncover the subtle hypercortisolism is the dexamethasone suppression test (DST). Case presentation: We report a case of SCS in a 62 years old Caucasian postmenopausal patient with a medical history of total thyroidectomy for Graves’ disease, post-surgical hypothyroidism, 7.4cm right pheochromocytoma status post partial right adrenalectomy, incidentally discovered pituitary macroadenoma (during imaging to look for subarachnoid hemorrhage), untreated type 2 diabetes mellitus (A1c 6.6% and stable for 1 year before treatment), hypertension, atrial fibrillation, cerebrovascular accident, and worsening migraines. Patient’s physical exam was mostly unremarkable; she had central obesity and bilateral lower extremity swelling. Pituitary work-up showed evidence of secondary hypogonadism and secondary hypothyroidism with elevated adrenocorticotropic hormone (ACTH) of 130 (AM range: 7.2-63) and cortisol of 12.6, at 11:52AM. Further work-up for hypercortisolism revealed non-suppressed 8AM cortisol (5.83mcg/dL) on the low dose DST and 49% suppression of 8AM cortisol and ACTH on the high dose DST. 24hour urinary cortisol was normal. Patient did not perform the midnight salivary cortisol. Patient subsequently underwent trans-sphenoidal resection of the pituitary macroadenoma. Pathology analysis of the pituitary mass showed weak to moderate immunoreactivity for ACTH. Conclusion: Our patient had abnormal DST but normal 24hour urine cortisol. We may have missed her SCS if we screened her only with a 24hour urine cortisol. This confirms the fact that dexamethasone suppression test should be the first test in the evaluation of subclinical Cushing’s syndrome.
Presentation: Thursday, June 15, 2023
THU015 Unilateral Adrenal Hyperplasia Causing ACTH-independent Hypercortisolism
Authors: Mogar Nikita , McConnell Megan A , Yu Run , Weinreb Jane Eileen 
Published: October 2023

Abstract
Disclosure: N. Mogar: None. M.A. McConnell : None. R. Yu: None. J.E. Weinreb: None.
Background: Adrenal cortical hyperplasia is defined radiographically as a non-malignant growth or enlargement of the adrenal glands. Adrenal hyperplasia is most commonly bilateral, with unilateral adrenal hyperplasia occurring less frequently. Unilateral adrenal hyperplasia has been associated with primary hyperaldosteronism, and there are only a few case reports describing unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism. Clinical Case: A 56-year-old man with sleep apnea was incidentally found to have a 4.6 cm left adrenal nodule found on computed tomography (CT) chest imaging. Adrenal CT revealed a heterogeneous 4.6 x 3.3 x3.7 cm left adrenal mass with internal calcifications and a portion of the mass measuring 38 Houndsfield units (HU). His 8AM serum cortisol level was 19.80 mcg/dL (5-23 mcg/dL). No ACTH level was collected; however, a serum DHEA-S level was 55 mcg/dL (32-240 mcg/dL). After low dose dexamethasone suppression test (LDDS), the serum cortisol level was elevated at 2.3 mcg/dL (&lt;1.8 mcg/dL). Repeat LDDS revealed a cortisol level of 2.9 mcg/dL. A 24-hour urine free cortisol level was 27.2 mcg/24h (4-50 mcg/24h). Testing for pheochromocytoma and hyperaldosteronism was negative. The patient had no historical or physical signs of Cushing’s syndrome and no signs of malignancy. Due to concerning features on adrenal CT imaging (tumor size &gt;4 cm, internal calcifications, and HU &gt;10), the patient underwent unilateral adrenalectomy. The patient did not receive intraoperative corticosteroids and remained normotensive post-operatively. However, his post-operative 8AM cortisol level was &lt;0.2 mcg/dL (5-23 mcg/dL) on two separate occasions. He was discharged on a short course of hydrocortisone, with eventual recovery of his hypothalamic-pituitary-adrenal (HPA) axis. Pathology revealed a diagnosis of cortical adrenal hyperplasia. Conclusion: The presence of postoperative hypocortisolemia demonstrates that this patient had ACTH-independent hypercortisolism. This case report would be one of few describing the rare diagnosis of unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism and would add to the sparse literature currently available on this condition. Additionally, this case report highlights the clinical significance of mild autonomous cortisol secretion (MACS); despite only having an unsuppressed cortisol level following LDDS, this patient was found to have a suppressed HPA axis after unilateral adrenalectomy requiring corticosteroids. Early identification and treatment of MACS and treatment of adrenal insufficiency following adrenalectomy is essential to prevent adverse events.
Presentation: Thursday, June 15, 2023