bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI281 Sexual Dimorphism In The LH Responses To Kisspeptin And Senktide Administration In Prepubertal Mice
Authors: Maione Luigi , Naule Lydie , Li Chloe , Magnuson Melissa , Young Jacques , Carroll Rona Stephanie , Kaiser Ursula B 
Published: October 2023

Abstract
Disclosure: L. Maione: Consulting Fee; Self; Pfizer, Inc., Ipsen. L. Naule: None. C. Li: None. M. Magnuson: None. J. Young: Consulting Fee; Self; Serono Laboratories, Ferring Pharmaceuticals. R.S. Carroll: None. U.B. Kaiser: None.
Introduction: The hypothalamic-pituitary-gonadal (HPG) axis is regulated by pulsatile GnRH secretion and its action on the anterior pituitary, leading to the synthesis and secretion of LH and FSH. KNDy neurons, expressing kisspeptin, neurokinin B and dynorphin A, are the GnRH/LH pulse generator and are key regulators of puberty and fertility. The HPG axis is active during prenatal and early postnatal life in humans and rodents, but then remains quiescent until puberty in both species. The response of gonadotropes to exogenous upstream GnRH signals such as kisspeptin and neurokinin during prepubertal development in mice is unknown. Aim: To conduct a systematic assessment of LH responsiveness to exogenous kisspeptin and to the neurokinin-3 receptor agonist senktide at regular intervals postnatally and across pubertal maturation in mice. Materials and Methods: Male and female J129Sv mice were treated with intraperitoneal injections of kisspeptin-10 (0.0023 nmol/g), senktide (0.023 nmol/g) or vehicle every 3 days from postnatal day (PND) 10 until completion of puberty. Serum LH was measured by an ultra-sensitive ELISA at baseline and 15 minutes after injection. Results: Prepubertal mice responded in an age-dependent and sexually dimorphic manner to kisspeptin and senktide. LH levels increased following kisspeptin stimulation in both sexes, but responses were higher in females than in males from PND10 to PND16. The highest response was observed at PND10, with a pattern of decreasing response with advancing age. Senktide induced a robust increase in serum LH in females from PND10 to PND16, with a decrease in response with age, similar to that observed after kisspeptin treatment. In contrast, in males there was no increase in serum LH in response to senktide at any age. No difference in the onset of puberty or body weight was observed across treatment groups. Conclusions: The assessment of serum LH levels following IP administration of kisspeptin and senktide in prepubertal male and female mice demonstrated distinct age and sexually-dimorphic patterns of LH responses to GnRH upstream signals. LH responses are maximal at early ages with a decreasing pattern overtime, and are higher in females than in males, suggesting a different distribution of kisspeptin/neurokinin receptors or the presence of different and/or additional restraining factors on GnRH/LH in the two sexes. These findings provide new evidence for sexual dimorphism of the HPG axis in mice early in postnatal life, prior to the onset of puberty.
Presentation: Friday, June 16, 2023
FRI311 GnRH Agonist Induced Pituitary Apoplexy In A Patient With Gonadotropinoma
Authors: Madahar Inderpreet , Khan Salwa , Hergenroeder Laurel , Skaff Brianna , Haider Adnan 
Published: October 2023

Abstract
Disclosure: I. Madahar: None. S. Khan: None. L. Hergenroeder: None. B. Skaff: None. A. Haider: None.
Introduction: GnRH therapy is commonly employed in patients with advanced prostate cancer. It acts as an agonist that binds to pituitary GnRH receptors. It acts via desensitization, downregulating FSH and LH production, and ultimately decreasing testicular steroidogenesis. Initial administration leads to transient stimulation of the pituitary which leads to elevated FSH and LH levels and increased production of estrogen and testosterone with eventual downregulation of the overall pathway. Case description: 80-year-old male with a past history of atrial fibrillation and OA was diagnosed with prostate cancer. Prostate adenocarcinoma Gleason score 7 (4+3) grade 3 was diagnosed by needle core biopsy five months prior to presentation. CT chest, abdomen, pelvis, and bone scan did not show evidence of metastatic disease. A week prior to starting Lupron therapy he was started on bicalutamide therapy. He received a dose of leuprolide (Elligard) as part of his chemoradiation therapy for his cancer. The patient went golfing after the treatment and within four hours he started noticing headaches and retroorbital pain. Headaches were sharp in quality, intensity 9 out of 10, and associated with nausea and vomiting. He later developed right-sided ptosis and double vision which progressively worsened after the next few hours. An initial CT scan of the head showed an enlarging pituitary mass which was followed MRI of the brain with and without contrast showed an enlarged pituitary mass and right cavernous sinus effacement of the optic chiasm. Anterior pituitary hormone functions were ordered, and the patient was started on stress-dose steroids. Transsphenoidal pituitary resection was done which the patient tolerated well pathology showed pituitary adenoma with pituitary apoplexy and the immunoprofile was compatible with gonadotroph adenoma. The adenoma cells were positive for synaptophysin, cam 5.2, GATA3, and FSH. A repeat MRI of the Sella three months after surgery showed a 9 mm nodule in the right aspect of the Sella. Anterior pituitary hormone levels done prior to surgery showed an IGF- 1 level of 204 ng/ml (Z score 1.5 SD). TSH and free T4 were in the normal range. Hydrocortisone was tapered and stopped 6 weeks after transsphenoidal surgery. Discussion: Lupron levels reach maximum concentration four hours after intramuscular administration. Initial pituitary stimulation by leuprolide administration causes the increased metabolic activity of the underlying adenoma which outgrows its blood supply, thus developing ischemic necrosis and subsequent hemorrhage. The majority of pituitary apoplexy develops in patients with previous undiagnosed pituitary adenomas. Should patients get central imaging to screen for pituitary macroadenoma before Lupron treatments to prevent this potentially life-threatening complication?
Presentation: Friday, June 16, 2023
FRI350 Prolonged Transient Central Diabetes Insipidus Induced By Traumatic Brain Injury
Authors: Marques Renata , Sharma Sapna , Flores Chang Bessy Suyin , Sajan Alen 
Published: October 2023

Abstract
Disclosure: R. Marques: None. S. Sharma: None. B.S. Flores Chang: None. A. Sajan: None.
Introduction: Central diabetes insipidus (CDI) is a rare complication of traumatic brain injury (TBI). Most cases of CDI due to TBI are transient and resolve within 2-5 days. We report a patient with prolonged transient CDI which lasted for 35 days after sustaining a gunshot wound to the head. Case Description: A 17-year-old male with no past medical history presented after gunshot wound in the head. He had comminuted fractures of the right temporal bone, right zygomatic arch, greater and lesser rings of sphenoid bone, right maxillary sinus, right medial orbital wall, right orbital floor and bilateral frontal sinuses. A computerized tomography of head showed subarachnoid haemorrhage of the frontal lobes as well as subdural haemorrhage of right parietal lobe, right falx cerebri and left cerebral hemisphere. On hospital day 2, he had an intracranial pressure monitor placed which was unremarkable. He underwent right hemicraniectomy with debridement and washout on hospital day 3. Shortly afterwards, his urine output increased to &gt;500 cc/hr with serum sodium of 172 mEq/L [135-145], serum osmolality 307 mOsmol/kg [270-295], and urine osmolality of 117 mOsm/kg [300-900]; consistent with CDI. He was acutely treated with intravenous desmopressin with resolution of hypernatremia. During the next five weeks of his 3-month hospitalization, he continued to have polyuria with specific gravity as low as 1.003 [1.005-1.030], and occasional hypernatremia, with a peak serum sodium of 150 mEq/L. Intranasal desmopressin as well as free water supplementation were given daily to alleviate his polyuria and hypernatremia. Evaluation of anterior pituitary function was normal except for decreased gonadotrophins. His polyuria resolved after five weeks, and labs showed urine osmolality of 530 mOsm/kg with serum sodium 138 mEq/L and urine specific gravity 1.010, consistent with resolution of CDI. Intranasal desmopressin was discontinued. His serum sodium remained stable without desmopressin for the next 7 weeks with serum sodium at discharge of 141 mEq/L. Discussion: The damage of the hypothalamic vasopressin-producing neurons, their axons or the posterior pituitary results in permanent post-TBI CDI. In cases of transient CDI, the pathogenesis is likely related to small vessel damage or inflammatory edema rather than direct neuronal damage. In our case, the patient initially developed hypernatremia and polyuria from acute CDI due to hemicraniectomy with debridement and washout. He continued to have prolonged transient CDI due to the extensive intracranial hemorrhage and edema. The CDI resolved with desmopressin (both intravenous and intranasal) and fluid replacement. Transient CDI is a rare complication intracranial haemorrhage. Our case highlights that the severity of TBI may correlate with the duration of transient CDI.
Presentation: Friday, June 16, 2023
FRI361 Insulinoma Presenting With Complete Heart Block
Authors: Campbell Ruth , Lawless Sarah Jean , MacNeill Briain , Brosnan Elizabeth , Bell Marcia J 
Published: October 2023

Abstract
Disclosure: R. Campbell: None. S.J. Lawless: None. B. MacNeill: None. E. Brosnan: None. M.J. Bell: None.
Background: Insulinomas are a rare functioning pancreatic neoplasm, causing hypoglycaemia, typically during the fasting state (1). The non-specific and varied presentations of this condition make it quite the elusive diagnosis. Clinical Case: A 32 year old female with multiple presentations to the hospital with loss of consciousness and fatigue was subsequently noted to have complete heart block with a 4.4 second pause due to ventricular standstill in the early morning on a holter monitor. She had a background history of temporal lobe epilepsy from the age of 17 and was on regular anti-epileptics. Following discussion with the electrophysiology team, a dual chamber pacemaker (PPM) was inserted. Two months following PPM insertion she was re-admitted with another collapse, however on this occasion a blood glucose level (BGL) was 1.7mmol/L, promoting investigation for a possible insulinoma. A 72hr fast provided biochemical evidence of same with a BGL of 1.6mmol/L within 24hrs, insulin level 72.7pmol/L and c-peptide 621pmol/L. She was commenced on Octreotide and Diazoxide while awaiting further work-up. A CT pancreas was normal, and she subsequently underwent an endoscopic ultrasound, which visualised an isoechoic lesion in the pancreatic mid-body. One year following her initial presentation she underwent enucleation of the pancreatic lesion and pathology confirmed an insulinoma. Her symptoms resolved and her pacemaker was subsequently removed after multidisciplinary discussion and a period of close observation with the device function turned off. Conclusion: To date there are no published case reports of an insulinoma presenting as complete heart block, however the phenomenon has been studied in animal models. Key learning points are the ambiguous nature of this diagnosis and the need to keep an open mind, particularly when other factors muddy the water, which in this case were cardiac arrhythmias and seizure disorder. Reference: (1) Okabayashi T, Shima Y, Sumiyoshi T, Kozuki A, Ito S, Ogawa Y, et al. Diagnosis and management of insulinoma. World journal of gastroenterology: WJG. 2013;19(6):829.
Presentation: Friday, June 16, 2023
THU171 Reference Intervals For Bioavailable IGF-I Values In Dutch Healthy Children, Adolescents And Young Adults
Authors: Pellikaan Karlijn , Elizabeth Melitza , Hokken-Koelega Anita C S , van den Berg Sjoerd Adrianus Antonius , de Graaff-Herder Laura 
Published: October 2023

Abstract
Disclosure: K. Pellikaan: None. M. Elizabeth: None. A.C. Hokken-Koelega: None. S.A. van den Berg: None. L. de Graaff-Herder: None.
Background: Immunoreactive ‘total’ IGF-I is the main biochemical marker for titration of growth hormone (GH) treatment. However, in several endocrine disorders like Prader-Willi syndrome (PWS) and Silver-Russell syndrome, total IGF-I levels are often higher than expected based on GH dose and clinical effects. When patients reach total IGF-I concentrations above +2SDS, fear of negative long-term effects makes clinicians reduce GH dose. This dose reduction often leads to a deterioration in body composition, growth (in children) and quality of life, which suggests that bioavailability of IGF-I is reduced in patients with these disorders. Measurement of bioavailable IGF-I could improve GH dose titration. However, use of bioavailable IGF-I assays has been hindered by the lack of proper reference intervals. We report reference intervals of bioavailable IGF-I in a large group of healthy children, adolescents and adults. Methods: Serum was collected of 260 Dutch healthy controls aged 1-21 years. Total IGF-I and unbound, bioavailable IGF-I were measured manually using Ansh Labs total and free IGF-I assays. We calculated male and female age-related reference intervals for total and bioavailable IGF-I. Results: We present male and female age-related reference intervals. Both total and bioavailable IGF-I increased with age and were significantly higher in females than in males (p &lt; 0.001). Conclusions: the reported reference intervals for bioavailable IGF-I concentrations will facilitate the use of bioavailable IGF-I levels as an alternative marker for GH dose titration in patients with disorders in which total IGF-I levels are unreliable.
Presentation: Thursday, June 15, 2023
FRI385 Influence Of Maternal Dietary Protein Precursor On Reproductive Endocrinology Of Neonatal Bovine Offspring
Authors: Thorson Jennifer F , Prezotto Ligia D 
Published: October 2023

Abstract
Disclosure: J.F. Thorson: None. L.D. Prezotto: None.
Bovine oogenesis and follicular maturation are initiated during in utero development, a process that is stringently orchestrated by the endocrine milieu. Of paramount importance are the three major biologically active estrogens: estron, estradiol, and estriol that are involved in the development and maintenance of germ cells. Previous work using the current model have revealed that maternal urea (protein precursor) supplementation reduces the ovarian follicular reserve without compromising the number of secondary and tertiary follicles. Therefore, we did not anticipate an influence of dietary treatment on biologically active estrogens. However, as the ovarian reserve is positively associated with circulating concentrations of anti-Mullerian hormone (AMH) we hypothesized that offspring from dams supplemented urea would have reduced circulating concentrations of AMH at birth. To characterize the effects of maternal urea supplementation, multiparous cows pregnant with female calves were individually-fed isocaloric dietary treatments consisting of chopped forage top-dressed with a control (0 g urea/animal/d) or urea (80 g urea/animal/d) pelleted supplement. Diets met or exceeded dietary requirements throughout gestation. Blood samples were collected from offspring at birth for the collection of plasma. Plasma was analyzed for concentration of estradiol, estrone, unconjugated estriol, and AMH using commercially available ELISA kits. The effect of maternal dietary treatment on concentration of hormones in offspring were evaluated by ANOVA. As expected, maternal dietary treatment did not influence circulating concentrations of estradiol (P = 0.41), estrone (P = 0.35), or unconjugated estriol (P = 0.31). However, it was not anticipated that maternal dietary treatment would have no effect on circulating concentrations of AMH (P = 0.97) as offspring of urea-supplemented dams had fewer primordial and primary follicles than offspring from control dams. From these results we infer that maternal urea supplementation induces precocious follicular activation and/or increases the number of follicles recruited during maturation through an AMH-independent mechanism. Moreover, these data illustrate that while offspring of dams offered urea throughout pregnancy have a reduction in primordial and primary follicles, the steroidogenic competence of secondary and tertiary follicles is no different than dams offered the control diet.
Presentation: Friday, June 16, 2023
FRI389 Granulosa Cell-specific Knockout Of Scnn1a Disturbs Estrus Cycle And Impairs Estrogen Production In Mice
Authors: Ma Xiyang , Xu Ruiyao , Que Yanting , Chen Junjiang , Ruan Ye Chun 
Published: October 2023

Abstract
Disclosure: X. Ma: None. R. Xu: None. Y. Que: None. J. Chen: None. Y. Ruan: None.
Estrogens are produced primarily by ovarian granulosa cells in females, the homeostasis of which is not only a prerequisite for female reproduction but also essential to the overall health. Studies suggested Na+ environment/intake in relation to ovarian functions, although the underlying mechanism remains unclear. In the present study, we explored possible expression and function of the epithelial Na+ channel (ENaC) in granulosa cells. We analyzed an available single-cell RNA sequencing database of human ovarian cells, mouse ovarian tissues as well as a human granulosa cell line (KGN), which showed ENaC expression and its channel activities (measured by patch-clamp) in granulosa cells. Since ENaCα (Scnn1a) is the rate-limiting subunit for ENaC to function, we established a granulosa cell-specific Scnn1a knockout mouse model (Scnn1afl/fl, Cyp19a1-Cre). In such a conditional knockout (cKO) model, the estrus cycle of the female mice at reproductive ages of 8 to 10-week-old was found to be disturbed with the ratio of proestrus/estrus versus metestrus/diestrus significantly higher (t-test, p &lt; 0.001) in cKO (1.8 ± 0.1, n = 8) compared to that of the Cre-negative control (Scnn1afl/fl, 1.0 ± 0.1, n = 8) mice. Histological analysis of the ovarian tissues showed a fewer (t-test, p &lt; 0.05) number of corpus luteum in cKO mice (1.9 ± 0.8 per ovary, n = 8) than that of the control mice (6.2 ± 1.5 per ovary, n = 6). We next isolated the granulosa cells from the mouse model and tested their responses to gonadotropins in vitro. In granulosa cells from the control mice, the estradiol level in the culture medium (measured by ELISA) was significantly increased by the treatment of FSH (100 ng/ml, 48 hours) and subsequent LH (100 ng/ml, 18 hours) as compared to that of cells without FSH/LH treatment (33.0 ± 12.3 vs. 5.1 ± 0.9 ng/ml, t-test, p &lt; 0.05, n = 6). Whereas, in cKO granulosa cells, no such elevation of estradiol level in response to FSH/LH was detected (7.6 ± 1.8 vs. 6.5 ± 1.3 ng/ml, t-test, p &gt; 0.05, n = 6), suggesting impaired estrogen production with ENaCα knockout. Consistently, quantitative PCR results showed significant downregulation of Cyp19a1 (-96.1 ± 0.9%), Lhcgr (-99.5 ± 0.1%) and Fshr (- 67.9 ± 7.2%), three key steroidogenic genes, in FSH/LH-treated cKO cells, as compared to that of FSH/LH-treated control cells (n = 6, t-test, p &lt; 0.05). Taken together, these results have suggested a previously undefined role of ENaC in granulosa cells for estrogen production in response to gonadotrophins maintaining female cycle homeostasis. This work was supported by National Natural Science Foundation of China (82071599).
Presentation: Friday, June 16, 2023
FRI390 The Effects Of Chronic Asprosin Administration On Ovarian Tissue
Authors: Kelestimur Haluk , Oz Zeynep Dila , Ozdede Mehmet Ridvan , Serhatlioglu Ihsan , Tektemur Nalan Kaya , Kacar Emine 
Published: October 2023

Abstract
Disclosure: H. Kelestimur: None. Z. Oz: None. M. Ozdede: None. I. Serhatlioglu: None. N. Kaya Tektemur: None. E. Kacar: None.
Purpose: Asprosin is a novel glucogenic and orexigenic hormone produced by the fibrillin 1 (FBN1) gene that is secreted by white adipose tissue during fasting. Fibrillins (FBNs) are structural and signalling proteins found mainly in the ovarian stroma, tunica albuginea and theca layers. The aim of this study was to determine the effects of asprosin on ovarian tissue in the female rats. Materials and methods: Twenty-four female Sprague-Dawley rats were randomly divided into 2 groups (n=12) as control and asprosin. Asprosin and control groups were given intraperitoneal saline at doses of 500 ng/kg and 1 ml/kg, respectively, at 14.00 every day for eight weeks. After the application, decapitation was performed, and the rapidly removed ovarian tissues were placed in a 10% formaldehyde solution for fixation. Formalin-fixed ovaries were dehydrated in a graded alcohol series and graded ethanol, respectively After that, all tissues were embedded in paraffin wax. The ovaries were cut into 5-µm sections and stained with hematoxylin and eosin (H&E) and also Masson trichrome staining. Ovarian follicular reserve and fibrosis were evaluated by light microscopy. The follicles were histologically classified as primordial, primary, secondary, and Graaf and all follicular structures were counted in each section. The fibrosis was evaluated with Masson’s trichrome staining and scored from 0 to 3 semi-quantitatively (0 = no fibrosis, 1 = low fibrosis, 2 = intermediate fibrosis, 3 = severe fibrosis). Results: In the asprosin group, unlike the control group, occasional congestion was observed in the vessels located in the ovarian medulla. Apart from this, no histopathological changes were found. An increase in fibrosis was detected in the ovarian sections of the asprosin group when compared to the control group (p = 0,035). In the light microscopic evaluation of the ovarian sections of the rats in the asprosin group, the primary and secondary follicle numbers were significantly higher than those in the control group (p = 0,008 and p = 0,047 respectively). However, the difference between the control and asprosin groups in terms of the primordial follicle, Graafian follicle and corpus luteum numbers were not statistically significant. Conclusion: Our results have shown that chronic asprosin administration causes an increase in the number of primary and secondary follicles, suggesting that changes in ovarian steroidogenesis and folliculogenesis depending on the application may lead to positive effects on female fertility.
Keywords: Asprosin, adipokine, ovarian follicle. Acknowledgement: This study was supported by TUBITAK (Project: 220S744).
Presentation: Friday, June 16, 2023