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Endocrines, Volume 5, Issue 1 (March 2024) – 8 articles

Cover Story (view full-size image): Current diabetes guidelines require numerous healthcare resources that are not easily accessible in rural areas, including various physician specialties, dietitians, certified diabetes educators, and a built environment consisting of hospitals, pharmacies, emergency care clinics, gyms, grocery stores, high speed internet, and diabetes prevention and diabetes self-management education and support programs. In addition, intensive lifestyle intervention weight loss programs require resources that are not readily available in rural areas. This leaves rural physicians and other rural healthcare professionals in a dilemma. With this in mind, some practical starting points are offered for rural physicians to help address the nutritional health of people with diabetes in rural areas. View this paper
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8 pages, 1165 KiB  
Communication
Protective Activities of Growth Hormone-Releasing Hormone Antagonists against Toxin-Induced Endothelial Injury
by Saikat Fakir and Nektarios Barabutis
Endocrines 2024, 5(1), 116-123; https://doi.org/10.3390/endocrines5010008 - 18 Mar 2024
Viewed by 574
Abstract
GHRH regulates the secretion of GH from the anterior pituitary gland, previously associated with cancer progression and inflammation. An emerging body of evidence suggests that GHRHAnt support endothelial barrier function, but the mechanisms mediating these events are not completely understood. In the present [...] Read more.
GHRH regulates the secretion of GH from the anterior pituitary gland, previously associated with cancer progression and inflammation. An emerging body of evidence suggests that GHRHAnt support endothelial barrier function, but the mechanisms mediating these events are not completely understood. In the present study, it is demonstrated that the GHRHAnt JV-1-36 counteracts barrier dysfunction due to LPS or LTA treatment in HUVECs, utilizing the Dextran–FITC assay. Moreover, it is shown in BPAECs that these bacterial toxins increase ROS generation, and that this effect is counteracted by JV-1-36, which reinstates the redox balance. The possible involvement of NEK2 in the beneficial activities of GHRHAnt in IFN-γ- and LPS-triggered hyperpermeability was also assessed, since that kinase is involved in inflammatory responses. NEK2 was increased in the inflamed cells, and JV-1-36 counteracted those endothelial events. Our data support the beneficial effects of GHRHAnt in toxin-induced endothelial injury. Full article
(This article belongs to the Special Issue Feature Papers in Endocrines: 2024)
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14 pages, 1040 KiB  
Review
Antagonism of Estrogen Receptor α-Driven Transcription Mediated by AP-1 in Breast Cancer Therapy
by Guy Leclercq
Endocrines 2024, 5(1), 102-115; https://doi.org/10.3390/endocrines5010007 - 6 Mar 2024
Viewed by 889
Abstract
The evolution of breast cancers results from the emergence of epithelial cell subpopulations containing variant Estrogen Receptor α which is able to bypass conventional treatments aimed at antagonizing the activity of this tumor-promoting receptor. The present investigation concerns a few estradiol derivates bearing [...] Read more.
The evolution of breast cancers results from the emergence of epithelial cell subpopulations containing variant Estrogen Receptor α which is able to bypass conventional treatments aimed at antagonizing the activity of this tumor-promoting receptor. The present investigation concerns a few estradiol derivates bearing substituents in position 11β that might not only contribute to the development of drugs to alleviate this unfortunate issue but that may be also helpful in identifying molecular aspects of resistance to this receptor in order to elaborate other therapeutic approaches. In this regard, AP-1 assisted and ERE-directed ERα transcriptions are demonstrated to be key factors in this area: AP-1 transcriptions are shown to antagonize ERE transcriptions, thereby limiting their tumor-promoting activity. This property results from a conformal change in the receptor, which is induced essentially by estrogenic ligands which, inserted into a cavity of ERα’s ligand-binding pocket, govern this regulatory mechanism. Flexible 11β side-chains favor this insertion, in contrast to their rigid counterparts, which counteract it; these properties give rise to strong estrogenic, SERM or SERD profiles. Suspected extracellular regulatory mechanisms resulting from these ligand-induced transcriptions are elaborated on in the present work in the context of breast cancer development. Full article
(This article belongs to the Special Issue Feature Papers in Endocrines 2023)
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15 pages, 314 KiB  
Review
Screening, Diagnosis, and Treatment of Patients with Binge Eating Disorder and Obesity: What the Endocrinologist Needs to Know
by Simonetta Marucci, Luca Busetto, Marco Chianelli, Alessandra Fusco, Maria Carpentieri, Marina Armellini, Francesco Tassone, Marcello Sciaraffia, Maria Chantal Ponziani, Anna Nelva and Carla Micaela Cuttica
Endocrines 2024, 5(1), 87-101; https://doi.org/10.3390/endocrines5010006 - 5 Feb 2024
Viewed by 1004
Abstract
Binge eating disorder (BED) is the most common eating disorder categorized in the DSM-V, but it is often not diagnosed in patients with obesity because it can be difficult to detect in these patients who often have altered eating patterns. In this narrative [...] Read more.
Binge eating disorder (BED) is the most common eating disorder categorized in the DSM-V, but it is often not diagnosed in patients with obesity because it can be difficult to detect in these patients who often have altered eating patterns. In this narrative review, we have highlighted the most recent findings in the screening, diagnosis, and treatment of patients with BED and obesity. The results of our search showed that many BED patients are not obese, and most people with obesity do not have binge behavior. In the diagnostic assessment of these patients, it is important to evaluate not only the clinical and nutritional status and the presence of medical comorbidities, but also the psychological signs and symptoms related to psychiatric comorbidities to define the appropriate diagnosis and the consequent level of treatment. Well-tolerated drugs with action on both body weight and binges can be useful as a second-line complement to cognitive behavioral therapy (CBT). Specific guidelines are needed to obtain consensus on appropriate recommendations in patients with obesity and BED approaching bariatric surgery, taking into account not only weight reduction and clinical data, but also eating behaviors. Identification of BED is important for targeting individuals at high risk of obesity, adverse metabolic patterns, and cardiovascular disease. The challenge is to also achieve lasting weight loss in patients with BED and concomitant obesity. Full article
(This article belongs to the Section Obesity, Diabetes Mellitus and Metabolic Syndrome)
15 pages, 302 KiB  
Review
Is Tirzepatide the New Game Changer in Type 2 Diabetes?
by Giuseppe Lisco, Olga Eugenia Disoteo, Vincenzo De Geronimo, Anna De Tullio, Vito Angelo Giagulli, Edoardo Guastamacchia, Giovanni De Pergola, Emilio Jirillo and Vincenzo Triggiani
Endocrines 2024, 5(1), 72-86; https://doi.org/10.3390/endocrines5010005 - 1 Feb 2024
Viewed by 979
Abstract
Background: Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS [...] Read more.
Background: Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. Aims: The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. Results: The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA1c levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). Conclusions: Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits. Full article
(This article belongs to the Special Issue Advances in Diabetes Care)
26 pages, 2487 KiB  
Review
Exploring the Endocrine Mechanisms in Adenomyosis: From Pathogenesis to Therapies
by Juliette d’Otreppe, Daniel Patino-García, Patryk Piekos, Matthieu de Codt, Diego D. Manavella, Guillaume E. Courtoy and Renan Orellana
Endocrines 2024, 5(1), 46-71; https://doi.org/10.3390/endocrines5010004 - 1 Feb 2024
Viewed by 3442
Abstract
Adenomyosis (ADM) is a multifaceted uterine pathology characterized by the ectopic infiltration of endometrial tissue into the myometrium, affecting approximately 20% of women in the reproductive age group seeking gynecological care. This condition manifests as a range of debilitating symptoms, including dysmenorrhea, menorrhagia, [...] Read more.
Adenomyosis (ADM) is a multifaceted uterine pathology characterized by the ectopic infiltration of endometrial tissue into the myometrium, affecting approximately 20% of women in the reproductive age group seeking gynecological care. This condition manifests as a range of debilitating symptoms, including dysmenorrhea, menorrhagia, impaired fertility, and heightened susceptibility to miscarriage and obstetric complications. Substantial research has been dedicated to exploring its underlying molecular mechanisms and developing non-invasive precision medical therapies. ADM is primarily characterized by a dysregulation in sex steroid hormone homeostasis, particularly estrogen and progesterone. However, emerging evidence suggests that additional endocrine mediators and disruptors may play contributory roles in the etiology of ADM. Genetic and epigenetic alterations of endocrine signaling pathways have been implicated as prevailing mechanisms underlying the development and progression of the disease. The present review aims to provide an updated and comprehensive overview of the current understanding of the pathophysiology of ADM, with a particular emphasis on the dysregulated hormonal milieu and the potential involvement of endocrine disruptors. By elucidating these intricate molecular mechanisms, this review seeks to pave the way for novel research directions in the development of targeted therapeutic strategies for ADM management. Full article
(This article belongs to the Section Female Reproductive System and Pregnancy Endocrinology)
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10 pages, 820 KiB  
Article
Modulatory Effects of Ethinyl Estradiol Plus Drospirenone Contraceptive Pill on Spontaneous and GnRH-Induced LH Secretion
by Alessandro D. Genazzani, Alessandra Sponzilli, Marcello Mantovani, Emma Fusilli, Francesco Ricciardiello, Elisa Semprini, Tommaso Simoncini and Christian Battipaglia
Endocrines 2024, 5(1), 36-45; https://doi.org/10.3390/endocrines5010003 - 23 Jan 2024
Viewed by 1069
Abstract
Background: Combined oral contraceptives (COCs) work mostly by preventing the pre-ovulatory gonadotropin surge, but the action of COCs on spontaneous episodic and GnRH (gonadotropin-releasing hormone)-induced LH (luteinizing hormone) release has been poorly evaluated. Oral contraceptives are known to act on the spontaneous hypothalamic–pituitary [...] Read more.
Background: Combined oral contraceptives (COCs) work mostly by preventing the pre-ovulatory gonadotropin surge, but the action of COCs on spontaneous episodic and GnRH (gonadotropin-releasing hormone)-induced LH (luteinizing hormone) release has been poorly evaluated. Oral contraceptives are known to act on the spontaneous hypothalamic–pituitary functions reducing both GnRH and gonadotropin release and blocking ovulation. Aim: To evaluate spontaneous and GnRH-induced LH release during both phases of the menstrual cycle or under the use of the contraceptive pill. Methods: A group of 12 women, subdivided into two groups, volunteered for the study. Group A (n = 6, controls) received no treatments, while Group B (n = 6) received a 21 + 7 combination of ethinyl-estradiol (EE) 30 µg + drospirenone (DRSP) 3 mg. Both groups were evaluated twice: Group A during follicular and luteal phases, Group B during pill assumption and during the suspension interval, performing a pulsatility test, GnRH stimulation test, and hormonal parameters evaluation. Spontaneous and GnRH-induced secretory pulses were evaluated, as well as the instantaneous secretory rate (ISR). Results: COC treatment lowered LH and FSH (follicle stimulating hormone) levels significantly if compared to the follicular phase of spontaneous cycles. During the suspension interval, hormone levels rapidly rose and became comparable to those of the follicular phase of the control group. The LH pulse frequency under COC administration during the suspension interval was similar to that observed during the follicular phase (2.6 ± 0.3 pulses/180 min and 2.3 ± 0.2 pulses/180 min, respectively). The GnRH-induced LH peaks were greater in amplitude and duration than those observed after ISR computation in both groups. The GnRH-induced LH release during the luteal phase of the control subjects was higher than in the follicular phase (51.2 ± 12.3 mIU/mL and 14.9 ± 1.8 mIU/mL, respectively). Conversely, subjects under COC showed a GnRH-induced LH response similar during COC and during the suspension interval. Conclusions: Our data support that the EE + DRSP preparation acts on both spontaneous pulsatile release and GnRH-induced LH release during the withdrawal period of the treatment, and that after 5–7 days from the treatment suspension, steroidal secretion from the ovary is resumed, such as that of androgens. This suggests that in hyperandrogenic patients, a suspension interval as short as 4 days might be clinically better. Full article
(This article belongs to the Special Issue Feature Paper in Reproductive Impairments and Pituitary Disorders)
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12 pages, 3388 KiB  
Article
Effects of Ghrelin on Plasminogen Activator Activity in Human Umbilical Vein Endothelial Cells
by Elisabetta Fiacco, Giovanna Notaristefano, Anna Tropea, Rosanna Apa and Rita Canipari
Endocrines 2024, 5(1), 24-35; https://doi.org/10.3390/endocrines5010002 - 8 Jan 2024
Viewed by 722
Abstract
Ghrelin and its growth hormone secretagogue receptor (GHSR) have been found in the placenta, both in endothelial and trophoblast cells. Ghrelin has been shown to decrease blood pressure in several systems and improve endothelial function by stimulating VEGF production. Because locally increased Ghrelin [...] Read more.
Ghrelin and its growth hormone secretagogue receptor (GHSR) have been found in the placenta, both in endothelial and trophoblast cells. Ghrelin has been shown to decrease blood pressure in several systems and improve endothelial function by stimulating VEGF production. Because locally increased Ghrelin was detected in the preeclamptic fetoplacental unit, we hypothesized its involvement in the fibrinolysis and vascular tone typically observed in preeclamptic patients. This study aimed to evaluate the synthesis of plasminogen activators (PAs), PA inhibitor-1 (PAI-1), and urokinase-type PA (uPA) receptor (uPAR) in human umbilical vein endothelial cells (HUVECs) since the components of the PA/plasmin system are vital players in the extracellular matrix remodeling process necessary for angiogenesis. HUVECs were treated for 24 h with increasing concentrations of Ghrelin (10−11–10−7 M) or IL-1β (0.1 ng/mL). PAs, PAI-1, and uPAR mRNAs were determined by real-time PCR and PA activity was determined by casein underlay. We demonstrated an increase in uPA, tissue-type PA (tPA), and uPAR mRNA; a reduction in PAI-1 mRNA in HUVECs treated with Ghrelin; and an increase in total uPA activity. In conclusion, our results suggest a potential compensatory physiological mechanism for Ghrelin in response to the maternal endothelial dysfunction observed in the preeclamptic fetoplacental unit. Full article
(This article belongs to the Section Female Reproductive System and Pregnancy Endocrinology)
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23 pages, 1957 KiB  
Review
Decoding Diabetes Nutritional Guidelines for Physicians in Underserved American Populations
by Owen J. Kelly, Elizabeth Deya Edelen, Anika Sharma, Karishma Kashyap, Radhika Patel, Samyukthaa Saiprakash, Ali Shah and Sriya Konduri
Endocrines 2024, 5(1), 1-23; https://doi.org/10.3390/endocrines5010001 - 5 Jan 2024
Viewed by 1203
Abstract
Medical (healthcare) deserts and food deserts, either separate or combined, exist in rural areas, globally. The physicians and other healthcare professionals who serve rural and other underserved populations, to some extent, also experience life in these areas. Dietary guidelines, from expert societies, for [...] Read more.
Medical (healthcare) deserts and food deserts, either separate or combined, exist in rural areas, globally. The physicians and other healthcare professionals who serve rural and other underserved populations, to some extent, also experience life in these areas. Dietary guidelines, from expert societies, for people with diabetes, have been helpful in guiding healthcare professionals through nutritional interventions. However, these guidelines are not designed for rural areas where healthcare resources are scarce, and access to the built environment for a healthy lifestyle and affordable healthy foods are not available. Therefore, the guidelines were reviewed, with rural physicians and healthcare professionals who work in underserved areas in mind, to assess their appropriateness. Based on the guidelines and other literature, potential solutions to guideline gaps are proposed to aid in providing nutritional therapy for the underserved. The overall goals are to improve the nutritional component of healthcare for underserved people with diabetes, and to begin the conversation around creating specific guidelines for rural physicians and other healthcare professionals, where patients are at a higher risk for diabetes. Full article
(This article belongs to the Section Obesity, Diabetes Mellitus and Metabolic Syndrome)
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