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International Journal of Molecular... Jan 2024Metabolic preconditioning, characterized by conditions like obesity and insulin resistance syndrome, disrupts hormonal balance. Elevated androgen levels stimulate...
Metabolic preconditioning, characterized by conditions like obesity and insulin resistance syndrome, disrupts hormonal balance. Elevated androgen levels stimulate excessive sebum production and follicular cell proliferation, leading to acne lesions. Similarly, thyroid hormone imbalances affect sebaceous gland activity, epidermal lipid composition, and skin cell turnover, impacting acne occurrence and severity. This study aimed to assess the potential contribution of metabolic and endocrine preconditions to acne development. A total of 389 patients diagnosed with acne were included and divided into three groups: the metabolic precondition group (MPG, N = 163, 41.9%), the endocrine precondition group (EPG, N = 162, 41.65%), and the control group (CG, N = 89, 22.88%). Data related to the degree of acne severity and comorbidities of interest were collected from the patients' medical records. In the groups with concomitant diseases, moderate and severe acne were significantly more prevalent (56.44% and 41.10% in MPG, and 35.80% and 61.11% in EPG) compared to the control group (5.61% and 4.89%). The most prevalent preconditions observed were insulin resistance syndrome in MPG (63.8%) and autoimmune thyroiditis in EPG (95.06%). Significant age-related differences in acne severity were found across all study groups ( < 0.05). In MPG, the age variable was significantly higher in the presence of mild acne, while in EPG, the age variable was significantly lower for the mild acne group. A positive association was observed between the severity of acne and insulin resistance syndrome, obesity, autoimmune thyroiditis, and hypothyroidism ( < 0.05). Risk analysis indicated a significantly higher risk (RR > 1, 95% CI RR > 1, < 0.001) of developing moderate and severe acne in the presence of these preconditions. The presence of both metabolic and endocrine preconditions significantly increased the likelihood of developing severe acne, leading to the hypothesis that both conditions may be contributing factors to the development of acne.
Topics: Humans; Insulin Resistance; Thyroid Diseases; Metabolic Syndrome; Acne Vulgaris; Hashimoto Disease; Thyroiditis, Autoimmune; Risk Assessment; Obesity
PubMed: 38255795
DOI: 10.3390/ijms25020721 -
Frontiers in Cell and Developmental... 2023Embryonic development and adult physiology are dependent on the action of steroid hormones. In particular, the reproductive system is reliant on hormonal signaling to... (Review)
Review
Embryonic development and adult physiology are dependent on the action of steroid hormones. In particular, the reproductive system is reliant on hormonal signaling to promote gonadal function and to ensure fertility. Here we will describe hormone receptor functions and their impacts on testicular function, focusing on a specific group of essential hormones: androgens, estrogens, progesterone, cortisol, and aldosterone. In addition to focusing on hormone receptor function and localization within the testis, we will highlight the effects of altered receptor signaling, including the consequences of reduced and excess signaling activity. These hormones act through various cellular pathways and receptor types, emphasizing the need for a multifaceted research approach to understand their critical roles in testicular function. Hormones exhibit intricate interactions with each other, as evidenced, for example, by the antagonistic effects of progesterone on mineralocorticoid receptors and cortisol's impact on androgens. In light of research findings in the field demonstrating an intricate interplay between hormones, a systems biology approach is crucial for a nuanced understanding of this complex hormonal network. This review can serve as a resource for further investigation into hormonal support of male reproductive health.
PubMed: 38250327
DOI: 10.3389/fcell.2023.1339385 -
Cancer Medicine Feb 2024Obesity and diabetes are associated inversely with low-grade prostate cancer risk and affect steroid hormone synthesis but whether they modify each other's impact on...
BACKGROUND
Obesity and diabetes are associated inversely with low-grade prostate cancer risk and affect steroid hormone synthesis but whether they modify each other's impact on prostate cancer risk remains unknown.
METHODS
We examined the independent associations of diabetes, body mass index (BMI), 'a body shape index' (ABSI), hip index (HI), circulating testosterone, sex hormone binding globulin (SHBG) (per one standard deviation increase) and oestradiol ≥175 pmol/L with total prostate cancer risk using multivariable Cox proportional hazards models for UK Biobank men. We evaluated multiplicative interactions (p ) and additive interactions (relative excess risk from interaction (p ), attributable proportion (p ), synergy index (p )) with obese (BMI ≥30 kg/m ) and diabetes.
RESULTS
During a mean follow-up of 10.3 years, 9417 incident prostate cancers were diagnosed in 195,813 men. Diabetes and BMI were associated more strongly inversely with prostate cancer risk when occurring together (p = 0.0003, p = 0.032, p = 0.020, p = 0.002). ABSI was associated positively in obese men (HR = 1.081; 95% CI = 1.030-1.135) and men with diabetes (HR = 1.114; 95% CI = 1.021-1.216). The inverse associations with obesity and diabetes were attenuated for high-ABSI ≥79.8 (p = 0.022, p = 0.008, p = 0.005, p <0.0001 obesity; p = 0.017, p = 0.047, p = 0.025, p = 0.0005 diabetes). HI was associated inversely in men overall (HR = 0.967; 95% CI = 0.947-0.988). Free testosterone (FT) was associated most strongly positively in normal weight men (HR = 1.098; 95% CI = 1.045-1.153) and men with diabetes (HR = 1.189; 95% CI = 1.081-1.308). Oestradiol was associated inversely in obese men (HR = 0.805; 95% CI = 0.682-0.951). The inverse association with obesity was stronger for high-FT ≥243 pmol/L (p = 0.040, p = 0.031, p = 0.002) and high-oestradiol (p = 0.030, p = 0.012, p <0.0001). The inverse association with diabetes was attenuated for high-FT (p = 0.008, p = 0.015, p = 0.009, p = 0.0006). SHBG was associated inversely in men overall (HR = 0.918; 95% CI = 0.895-0.941), more strongly for high-HI ≥49.1 (p = 0.024).
CONCLUSIONS
Obesity and diabetes showed synergistic inverse associations with prostate cancer risk, likely involving testosterone reduction for diabetes and oestrogen generation for obesity, which were attenuated for high-ABSI. HI and SHBG showed synergistic inverse associations with prostate cancer risk.
Topics: Male; Humans; Biological Specimen Banks; Somatotypes; UK Biobank; Testosterone; Diabetes Mellitus; Estradiol; Obesity; Prostatic Neoplasms
PubMed: 38234143
DOI: 10.1002/cam4.6918 -
JCEM Case Reports Jan 2024Estrogen-secreting adrenocortical carcinoma (ACC) is exceedingly rare, representing 1% to 2% of all ACCs. We present a case of a 65-year-old man diagnosed with an...
Estrogen-secreting adrenocortical carcinoma (ACC) is exceedingly rare, representing 1% to 2% of all ACCs. We present a case of a 65-year-old man diagnosed with an estrogen-secreting, 4.3-cm right adrenal mass discovered during work-up for bilateral gynecomastia. Gynecomastia and hyperestrogenism resolved after laparoscopic adrenalectomy, and pathology was reported as adrenocortical adenoma. However, 5 years later, he again developed bilateral gynecomastia because of recurrent hyperestrogenism. Imaging revealed multiple metastases in the abdomen. Urine steroid profiling demonstrated increased androgen precursors, androgen metabolites, and glucocorticoid precursors. Ultrasound-guided biopsy of one of the metastases confirmed ACC. Initial therapy included debulking surgery with removal of metastatic lesions. Mitotane therapy was initiated 4 weeks later along with hydrocortisone for anticipated mitotane-induced adrenal insufficiency. Histopathology from the adrenalectomy specimen 5 years earlier was rereviewed and confirmed ACC. Estrogen-secreting adrenal tumors are exceedingly rare, and the majority are malignant. This case underlines the importance of making an initial accurate diagnosis of adrenal malignancy that allows better surgical planning and appropriate monitoring. Indeterminate imaging characteristics of the adrenal mass, as well as the presentation with estrogen excess, suggested an elevated risk for ACC. Initial pathology-based misdiagnosis illustrates the need for an expert adrenal pathologist to review these rare tumors.
PubMed: 38192879
DOI: 10.1210/jcemcr/luad143 -
The Journal of Dermatological Treatment Dec 2024The recognition of an association between the development of acne vulgaris (AV) and pubertal hormonal changes during adolescence dates back almost 100 years. Since... (Review)
Review
The recognition of an association between the development of acne vulgaris (AV) and pubertal hormonal changes during adolescence dates back almost 100 years. Since these formative observations, a significant role of circulating hormones in the pathophysiology of AV and other cutaneous disorders has been established. This review article aims to provide an overview of clinical and preclinical evidence supporting the influences of androgens on the skin and their therapeutic importance in AV pathophysiology. The cutaneous effects of hormones are attributable, to a large extent, to the influence of steroid hormones, particularly androgens, on sebocyte development and sebum production in both sexes. Androgen-mediated excess sebum production is implicated as a necessary early step in AV pathophysiology and is therefore considered an important therapeutic target in AV treatment. Although the local production and/or activity of androgens within the skin is believed to be important in AV pathophysiology, it has received limited therapeutic attention. We have summarized the current evidence in support of the therapeutic benefits of targeted hormonal treatment to decrease androgen-stimulated sebum production for the effective and safe treatment of AV in both male and female patients.
Topics: Adolescent; Humans; Female; Male; Androgens; Sebum; Skin; Acne Vulgaris; Dermatitis
PubMed: 38192024
DOI: 10.1080/09546634.2023.2298878 -
Journal of Trace Elements in Medicine... May 2024Cobalt (Co) is known to interfere with iron (Fe) metabolism that is essential for differentiating male germ cells. Our aim was to study the effect of developmental...
INRODUCTION
Cobalt (Co) is known to interfere with iron (Fe) metabolism that is essential for differentiating male germ cells. Our aim was to study the effect of developmental chronic cobalt exposure on mouse testis through changes in iron homeostasis in adulthood.
METHODS
Pregnant ICR mice were exposed to 75 mg (low dose) or 125 mg (high dose)/kg b.w. cobalt chloride (CoCl) with drinking water for 3 days before delivery and treatment continued until postnatal day 90 of the pups. Age-matched control animals obtained regular tap water. Testes of control and Co-treated mice were processed for immunohistochemistry and inductively coupled plasma mass spectrometry. Sperm count was performed.
RESULTS
Chronic CoCl administration resulted in significant dose-dependent Co accumulation in sera and testes of the exposed mice. Fe content also showed a significant increase in sera and testes compared to the untreated controls. Surprisingly, testes of low dose-treated mice had ∼ 2.7-fold higher Fe content compared to those exposed to the high dose. A significant dose-dependent reduction in relative testis weight by 18.8% and by 37.7% was found after treatment with low and high dose CoCl, respectively was found. Our study demonstrated that developmental chronic exposure to CoCl affected cellular composition of the testis manifested by germ cell loss and low sperm count, accompanied by altered androgen response in Sertoli cells (loss of stage-specific expression of androgen receptor). A possible mechanism involved is iron accumulation in the testis that was associated with altered ferroportin-hepcidin localization in seminiferous tubules depleted in germ cells. As a protective mechanism for germ cells in condition of iron excess, ferroportin was distributed in Sertoli cells around elongating spermatids. Similar changes in expression of transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1) implied that both factors of testicular Fe homeostasis are closely related. Outside the seminiferous tubules, Leydig cells localized ferroportin, hepcidin, DMT1 and TfR1 thus they could be considered as a main site for iron metabolism.
CONCLUSION
Our data suggest that Co exerts its effects on the testis by indirect mechanism possibly through alteration in Fe homeostasis.
Topics: Pregnancy; Female; Male; Mice; Animals; Testis; Hepcidins; Mice, Inbred ICR; Semen; Cobalt; Iron
PubMed: 38176318
DOI: 10.1016/j.jtemb.2023.127372 -
Current Obesity Reports Mar 2024The goal of the present review is to address the main adiposity-related alterations in Polycystic Ovary Syndrome (PCOS) focusing on hypothalamic-pituitary-ovarian... (Review)
Review
Hypothalamic-Ovarian axis and Adiposity Relationship in Polycystic Ovary Syndrome: Physiopathology and Therapeutic Options for the Management of Metabolic and Inflammatory Aspects.
PURPOSE OF REVIEW
The goal of the present review is to address the main adiposity-related alterations in Polycystic Ovary Syndrome (PCOS) focusing on hypothalamic-pituitary-ovarian (H-P-O) axis and to provide an overview of nutraceutical and pharmacological therapeutic strategies.
RECENT FINDINGS
Female reproduction is a complex and delicate interplay between neuroendocrine signals involving the H-P-O axis. Elements that disrupt the balance of these interactions can lead to metabolic and reproductive disorders, such as PCOS. This disorder includes menstrual, metabolic, and biochemical abnormalities as well as hyperandrogenism, oligo-anovulatory menstrual cycles, insulin resistance, and hyperleptinemia which share an inflammatory state with other chronic diseases. Moreover, as in a self-feeding cycle, high androgen levels in PCOS lead to visceral fat deposition, resulting in insulin resistance and hyperinsulinemia, further stimulating ovarian and adrenal androgen production. In fact, regardless of age and BMI, women with PCOS have more adipose tissue and less lean mass than healthy women. Excessive adiposity, especially visceral adiposity, is capable of affecting female reproduction through direct mechanisms compromising the luteal phase, and indirect mechanisms as metabolic alterations able to affect the function of the H-P-O axis. The intricate crosstalk between adiposity, inflammatory status and H-P-O axis function contributes to the main adiposity-related alterations in PCOS, and alongside currently available hormonal treatments, nutraceutical and pharmacological therapeutic strategies can be exploited to treat these alterations, in order to enable a more comprehensive synergistic and tailored treatment.
Topics: Female; Humans; Polycystic Ovary Syndrome; Insulin Resistance; Adiposity; Androgens; Hyperandrogenism; Obesity
PubMed: 38172476
DOI: 10.1007/s13679-023-00531-2 -
JCEM Case Reports Jan 2024Glucocorticoid resistance syndrome is a rare genetic condition characterized by generalized or partial target-tissue insensitivity to glucocorticoids and a consequent...
Glucocorticoid resistance syndrome is a rare genetic condition characterized by generalized or partial target-tissue insensitivity to glucocorticoids and a consequent hyperactivation of the hypothalamic-pituitary-adrenal axis. Clinical manifestations may include mineralocorticoid and/or androgen excess without manifestations of Cushing syndrome. At a cellular level, glucocorticoid actions are mediated by the nuclear glucocorticoid receptor encoded by the gene. To date, only 33 glucocorticoid receptor loss-of-function pathogenic variants have been associated with glucocorticoid resistance syndrome. The gene has 2 known disease-causing mechanisms: haploinsufficiency and negative dominance. We describe a mother and her son with a mild hyperandrogenic phenotype and a novel genetic variant of the gene predicting a truncated protein and causing glucocorticoid resistance syndrome. To date, no accurate genotype-phenotype correlation has been found.
PubMed: 38170043
DOI: 10.1210/jcemcr/luad153 -
Journal of Multidisciplinary Healthcare 2023The use of anabolic androgenic steroids (AAS) for strength training and muscle building is a widespread practice among athletes and young individuals. Athletes and... (Review)
Review
The use of anabolic androgenic steroids (AAS) for strength training and muscle building is a widespread practice among athletes and young individuals. Athletes and bodybuilders are using these substances for various purposes, such as enhancing muscle mass, strengthening their bodies, and enhancing their performances. AAS exert a wide range of physiological effects that result in the activation of central signaling, resulting in adverse effects. Moreover, excessive use of AAS which can be categorized as AAS abuse; is linked to biological and psychological pathologies, which can lead to mortality. Complications arising from steroid abuse involve both cellular and physiological complications. Cellular complications arise when activation of signaling proteins like mTOR, Akt, etc. leads to alteration in protein synthesis pathways, cell cycle, oxidative stress, and apoptosis, contributing to damage at the cellular level. Physiological complications are evident with cardiovascular pathologies, including an altered lipid profile, cardiac hypertrophy, hypogonadism after discontinuation of AAS, and modulation of GABA receptors in the brain, all contributed by the androgen receptor signaling. Clinical complications budding from these altered physiological processes lead to clinical effects like testicular dysfunction, acne, gynecomastia, and neuropsychiatric disorders. Despite potential therapeutic benefits, AAS use is prohibited by the World Anti-Doping Agency (WADA) due to concerns over adverse health effects. This review highlights the molecular mechanisms, physiological processes, and clinical complications arising from the excessive use of AAS among athletes.
PubMed: 38170017
DOI: 10.2147/JMDH.S439384