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Journal of Ovarian Research Jan 2024For women of childbearing age, the biggest problem caused by polycystic ovary syndrome (PCOS) is infertility, which is mainly caused by anovulation, abnormal follicular...
BACKGROUND
For women of childbearing age, the biggest problem caused by polycystic ovary syndrome (PCOS) is infertility, which is mainly caused by anovulation, abnormal follicular development, proliferation of small antral follicles, and cystic follicles. The mechanism underlying its occurrence is not clear. The abnormal proliferation and development of follicles in PCOS patients is a complex process, which is affected by many factors. The objective of this study was to investigate the relationship between the Hippo pathway and follicular development in PCOS, and to further explore this relationship by using the YAP inhibitor verteporfin (VP).
METHOD
30 3-week-old BALB/C female rats were randomly divided into control group (n = 10), DHEA group (n = 10) and DHEA + VP group (n = 10). The morphology of ovary and the degree of follicular development were observed by HE staining, and the expression and location of AMH in ovarian follicles were observed by immunofluorescence. The ovarian reserve function index AMH, cell proliferation index PCNA and the ratio of Hippo pathway related proteins MST, LATS, YAP, P-YAP and P-YAP/YAP were detected by Western blot.
RESULTS
After dividing 30 3-week-old female mice into control, dehydroepiandrosterone (DHEA; model of PCOS), and DHEA + VP groups, we found that the number of small follicles increased in the DHEA group compared to the control group. Additionally, in the DHEA group compared to the control group, anti-müllerian hormone (AMH; ovarian reserve index) increased, proliferating cell nuclear antigen (PCNA; cell proliferation index) decreased, and upstream (MST and LATS) and downstream (YAP and p-YAP) proteins in the Hippo pathway increased, though the p-YAP/YAP ratio decreased. VP ameliorated the increases in AMH, MST, LATS, YAP and p-YAP, but did not ameliorate the decrease in the p-YAP/YAP ratio.
CONCLUSIONS
This study indicates that the increased small follicles in the ovaries and changes in ovarian reserve and cell proliferation may be closely related to Hippo pathway activation. This suggests that the Hippo pathway may be an important pathway affecting the proliferation and development of follicles and the occurrence of PCOS.
Topics: Humans; Female; Rats; Animals; Mice; Polycystic Ovary Syndrome; Proliferating Cell Nuclear Antigen; Hippo Signaling Pathway; Mice, Inbred BALB C; Anti-Mullerian Hormone; Dehydroepiandrosterone
PubMed: 38216976
DOI: 10.1186/s13048-023-01305-z -
The Journal of Clinical Endocrinology... Nov 2023Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in...
CONTEXT
Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in general populations.
OBJECTIVE
To investigate if a 2-year lifestyle intervention influences circulating androgen concentrations and sexual maturation in a general population of children.
METHODS
We conducted a 2-year physical activity and dietary intervention study in which 421 prepubertal and mostly normal-weight 6- to 9-year-old children were allocated either to a lifestyle intervention group (119 girls, 132 boys) or a control group (84 girls, 86 boys). The main outcome measures were serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone concentrations, and clinical adrenarchal and pubertal signs.
RESULTS
The intervention and control groups had no differences in body size and composition, clinical signs of androgen action, and serum androgens at baseline. The intervention attenuated the increase of DHEA (P = .032), DHEAS (P = .001), A4 (P = .003), and testosterone (P = .007) and delayed pubarche (P = .038) in boys but it only attenuated the increase of DHEA (P = .013) and DHEAS (P = .003) in girls. These effects of lifestyle intervention on androgens and the development of pubarche were independent of changes in body size and composition, but the effects of intervention on androgens were partly explained by changes in fasting serum insulin.
CONCLUSION
A combined physical activity and dietary intervention attenuates the increase of serum androgen concentrations and sexual maturation in a general population of prepubertal and mostly normal-weight children, independently of changes in body size and composition.
Topics: Child; Female; Humans; Male; Adrenarche; Androgens; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Puberty; Testosterone; Exercise; Diet, Healthy
PubMed: 37329220
DOI: 10.1210/clinem/dgad367 -
Cells Mar 2022Primary biliary cholangitis (PBC) is a rare chronic cholestatic and immune-mediated liver disease of unknown aetiology that targets intrahepatic bile duct cells...
Primary biliary cholangitis (PBC) is a rare chronic cholestatic and immune-mediated liver disease of unknown aetiology that targets intrahepatic bile duct cells (cholangiocytes) and primarily affects postmenopausal women, when their estrogen levels sharply decrease. An impaired cholangiocyte response to estrogen characterizes the terminal stage of the disease, as this is when an inefficiency of cholangiocyte proliferation, in balancing the loss of intrahepatic bile ducts, is observed. Here, we report that the estrogen precursor dehydroepiandrosterone (DHEA) and its sulfate metabolites, DHEA-S and 17 β-estradiol, enhance the proliferation of cholangiocytes and hepatocytes in vitro. Flow cytometry analysis showed that DHEA and DHEA-S decreased glyco-chenodeoxycholic acid (GCDC)-driven apoptosis in cholangiocytes. Cell viability assay (MTT) indicated that ER-α, -β, and the G-protein-coupled estrogen receptor, are involved in the protection of DHEA against oxidative stress in cholangiocytes. Finally, immunoblot analysis showed an elevated level of steroid sulfatase and a reduced level of sulfotransferase 1E1 enzymes, involved in the desulfation/sulfation process of estrogens in cirrhotic PBC, and primary sclerosis cholangitis (PSC) liver tissues, another type of chronic cholestatic and immune-mediated liver disease. Taken together, these results suggest that DHEA can prevent the deleterious effects of certain potentially toxic bile acids and reactive oxygen species, delaying the onset of liver disease.
Topics: Apoptosis; Dehydroepiandrosterone; Estrogens; Female; Hepatocytes; Humans; Liver Diseases; Oxidative Stress; Receptors, G-Protein-Coupled
PubMed: 35326489
DOI: 10.3390/cells11061038 -
Clinical Interventions in Aging 2014Given demographic evolution of the population in modern societies, one of the most important health care needs is successful aging with less frailty and dependency.... (Review)
Review
Given demographic evolution of the population in modern societies, one of the most important health care needs is successful aging with less frailty and dependency. During the last 20 years, a multitude of anti-aging practices have appeared worldwide, aiming at retarding or even stopping and reversing the effects of aging on the human body. One of the cornerstones of anti-aging is hormone replacement. At present, women live one third of their lives in a state of sex-hormone deficiency. Men are also subject to age-related testosterone decline, but andropause remains frequently under-diagnosed and under-treated. Due to the decline of hormone production from gonads in both sexes, the importance of dehydroepiandrosterone (DHEA) in steroid hormone production increases with age. However, DHEA levels also decrease with age. Also, growth hormone age-associated decrease may be so important that insulin growth factor-1 levels found in elderly individuals are sometimes as low as those encountered in adult patients with established deficiency. Skin aging as well as decreases in lean body mass, bone mineral density, sexual desire and erectile function, intellectual activity and mood have all been related to this decrease of hormone production with age. Great disparities exist between recommendations from scientific societies and actual use of hormone supplements in aging and elderly patients. In this article, we review actual data on the effects of age related hormone decline on the aging process and age-related diseases such as sarcopenia and falls, osteoporosis, cognitive decline, mood disorders, cardiovascular health and sexual activity. We also provide information on the efficiency and safety of hormone replacement protocols in aging patients. Finally, we argue on future perspectives of such protocols as part of everyday practice.
Topics: Aging; Dehydroepiandrosterone; Estrogens; Hormone Replacement Therapy; Human Growth Hormone; Humans; Off-Label Use; Progesterone; Testosterone
PubMed: 25092967
DOI: 10.2147/CIA.S48918 -
European Child & Adolescent Psychiatry Aug 2023Although the link between androgens and depression is well established in adults, the effects of cofactors on this association are less clearly understood, particularly... (Observational Study)
Observational Study
Although the link between androgens and depression is well established in adults, the effects of cofactors on this association are less clearly understood, particularly in youth. Epidemiological cohort study of adolescents in Dresden, Germany. Analyses comprised data of 985 individuals assessed at baseline and of 512 individuals at 1-year follow-up. We investigated multivariable regression models for cross-sectional and longitudinal associations of hair testosterone, dehydroepiandrosterone (DHEA), and their cortisol ratios with 12-month diagnoses of major depressive disorder (MDD) and MDD without any anxiety disorder assessed with standardized diagnostic interview (DIA-X-5), and with dimensional depression scores (PHQ-9, PROMIS), separately for males and females. The potential moderating effect of social support was determined. Cross-sectional analyses yielded inverse associations of testosterone and DHEA with MDD and MDD without any anxiety disorders in males. In cross-sectional and longitudinal analyses, baseline ratio cortisol/DHEA was significantly, inversely associated to PROMIS-depression in males. Only cross-sectional associations for ratio cortisol/DHEA and PROMIS-depression remained significant after Bonferroni-Holm correction. No robust associations were observed in female participants. Social support exerted no consistent moderating effect on the investigated association. The present observational cohort study showed no consistent association of hair androgen concentrations with depressive disorders in adolescents. However, findings provide some support for the association between the cortisol/DHEA ratio and depression in males. Longitudinal research designs in large samples are needed to understand the interplay between androgens, depression, and developmental and social factors in youth.
Topics: Adult; Male; Humans; Adolescent; Female; Androgens; Dehydroepiandrosterone; Depressive Disorder, Major; Cohort Studies; Cross-Sectional Studies; Hydrocortisone; Testosterone; Hair
PubMed: 35112167
DOI: 10.1007/s00787-021-01929-w -
Journal of Aging and Physical Activity Apr 2023Age-related changes affect the ratio between two steroid hormones of the hypothalamic-pituitary-adrenal axis, cortisol and dehydroepiandrosterone (sulfate) (DHEA[S]).... (Meta-Analysis)
Meta-Analysis
Age-related changes affect the ratio between two steroid hormones of the hypothalamic-pituitary-adrenal axis, cortisol and dehydroepiandrosterone (sulfate) (DHEA[S]). Physical activity (PA) may buffer the effects of chronic stress and counteract the aging decline of DHEA(S). Therefore, a systematic review was conducted to understand how PA influences physiological markers of cortisol and/or DHEA(S) and whether there is a difference in observational associations or experimental effects in older adults aged 65 years and older. A narrative synthesis was performed on nine observational studies, and meta-analyses were performed on 22 randomized controlled trials. There was low- to moderate-quality evidence that regular PA beneficially reduces cortisol and increases DHEA(S) levels. Subgroup analyses showed no clinically important differences between men and women, different exercise modalities, or health states. The findings cautiously suggest that regular PA of older adults' own choice that they find enjoyable could be recommended to improve cortisol and/or DHEA(S) levels.
Topics: Male; Humans; Female; Aged; Hydrocortisone; Dehydroepiandrosterone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Exercise; Sulfates
PubMed: 35981715
DOI: 10.1123/japa.2021-0501 -
Neuropharmacology Apr 2021Stress and trauma exposure disturbs stress regulation systems and thus increases the vulnerability for stress-related disorders which are characterized by negative... (Review)
Review
Stress and trauma exposure disturbs stress regulation systems and thus increases the vulnerability for stress-related disorders which are characterized by negative affect, including major depressive disorder, anxiety disorders and posttraumatic stress disorder. Similarly, stress and trauma exposure results in increased vulnerability to problematic alcohol use and alcohol use disorder, especially among women, who are more likely to drink to cope with negative affect than their male counterparts. Given these associations, the relationship between stress-related disorders and alcohol use is generally stronger among women leading to complex comorbidities across these disorders and alcohol misuse. This review highlights the therapeutic potential for progestogen- and androgen-derived neurosteroids, which affect both stress- and alcohol-related disorders, to target the overlapping symptoms related to negative affect. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'
Topics: Affect; Alcohol-Related Disorders; Androgens; Dehydroepiandrosterone; Estradiol; Female; Humans; Male; Neurosteroids; Pregnanolone; Progesterone; Progestins; Sex Factors; Stress Disorders, Traumatic; Testosterone
PubMed: 33600842
DOI: 10.1016/j.neuropharm.2021.108499 -
Pediatric Research Aug 2023Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune...
BACKGROUND
Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited.
METHODS
Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic disadvantage) early-life adversities with salivary inflammatory biomarkers (IL-1β, IL-6, IL-8, and TNF-α) and hair HPA markers (cortisol, cortisone, and dehydroepiandrosterone) were examined in two samples of young U.S. children (N = 142; N = 145).
RESULTS
Children exposed to higher SES-D had higher levels of TNF-α (B = 0.13, p = 0.011), IL-1β (B = 0.10, p = 0.033), and DHEA (B = 0.16, p = 0.011). Higher family dysfunction was associated with higher cortisol (B = 0.08, p = 0.033) and cortisone (B = 0.05, p = 0.003). An interaction between SES-D and family dysfunction was observed for cortisol levels (p = 0.020) whereby children exposed to lower/average levels of SES-D exhibited a positive association between family dysfunction and cortisol levels, whereas children exposed to high levels of SES-D did not. These findings were partially replicated in the second sample.
CONCLUSIONS
Our results indicate that these biological response systems may react differently to different forms of early-life adversity.
IMPACT
Different forms of early-life adversity have varied stress signatures, and investigations of early-life adversities with inflammation and HPA markers are lacking. Children with higher socioeconomic disadvantage had higher TNF-α, IL-1β, and DHEA. Higher family dysfunction was associated with higher hair cortisol and cortisone levels, and the association between family dysfunction and cortisol was moderated by socioeconomic disadvantage. Biological response systems (immune and endocrine) were differentially associated with distinct forms of early-life adversities.
Topics: Humans; Child; Hydrocortisone; Cortisone; Tumor Necrosis Factor-alpha; Stress, Psychological; Saliva; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Dehydroepiandrosterone
PubMed: 36650307
DOI: 10.1038/s41390-022-02415-y -
PloS One 2021The goal of the current study was to create reference intervals and values for several common and one potential novel physiological indicators of animal welfare for four...
The goal of the current study was to create reference intervals and values for several common and one potential novel physiological indicators of animal welfare for four species of cetaceans. The subjects included 189 bottlenose dolphins (Tursiops truncatus), 27 Indo-Pacific bottlenose dolphins (Tursiops aduncus), eight Pacific white-sided dolphins (Lagenorhynchus obliquidens), and 13 beluga whales (Delphinapterus leucas) at Alliance of Marine Mammal Parks and Aquariums and/or Association of Zoos and Aquariums accredited facilities. During two sampling time periods between July and November of 2018 and between January and April of 2019, fecal samples were collected weekly for five weeks from all animals. Samples were processed and analyzed using enzyme immunoassay for fecal cortisol, aldosterone, and dehydroepiandrosterone (DHEA) metabolites. Linear mixed models were used to examine demographic and time factors impacting hormone metabolite concentrations. Age, sex, and time of year were all significant predictors for some of the models (p < 0.01). An iOS mobile application ZooPhysioTrak was created for easy access to species-specific reference intervals and values accounting for significant predictors. For facilities without access to this application, additional reference intervals and values were constructed without accounting for significant predictors. Information gained from this study and the use of the application can provide reference intervals and values to make informed management decisions for cetaceans in zoological facilities.
Topics: Age Factors; Aldosterone; Animals; Beluga Whale; Bottle-Nosed Dolphin; Dehydroepiandrosterone; Dolphins; Feces; Female; Hydrocortisone; Male; Reference Values; Seasons; Sex Factors
PubMed: 34460862
DOI: 10.1371/journal.pone.0250331 -
Frontiers in Endocrinology 2022Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disease. The gut microbiota is highly correlated with androgen secretion and insulin...
Effects of dehydroepiandrosterone alone or in combination with a high-fat diet and antibiotic cocktail on the heterogeneous phenotypes of PCOS mouse models by regulating gut microbiota.
OBJECTIVE
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disease. The gut microbiota is highly correlated with androgen secretion and insulin resistance (IR), which are two potential major pathogenic mechanisms of PCOS. Currently, an antibiotic cocktail (ABX) is often used to construct pseudo germ-free mouse models for studies on the gut microbiota and PCOS. Our work aimed to study the effects of dehydroepiandrosterone (DHEA), a high-fat diet (HFD) and ABX on the heterogeneous phenotypes of PCOS mouse models by regulating the gut microbiota.
METHODS
PCOS mouse models were established by subcutaneous injection of DHEA alone or in combination with a HFD in wild-type and pseudo germ-free mice. The changes in ovary morphology and sex hormonal and glycolipid metabolic parameters were evaluated.
RESULTS
Wild-type mice treated with DHEA or DHEA+HFD showed a PCOS-like phenotype of hyperandrogenism, anovulation and polycystic ovaries. The former was combined with hyperinsulinemia and IR, while the latter was combined with glucolipid metabolic disorders, extremely heterogeneous hyperinsulinemia and IR. The phenotype of PCOS mice, especially the metabolic parameters, was correlated with the gut microbiota. The pseudo germ-free mice treated with DHEA or DHEA+HFD also showed a PCOS-like phenotype. However, DHEA could not induce hyperinsulinemia or IR in pseudo germ-free mice. Pseudo germ-free mice treated with DHEA+HFD exhibited decreased serum AMH level, glucolipid metabolic disorders and IR. Compared with the wild-type mice, the pseudo germ-free mice treated with DHEA showed significantly higher testosterone and lipid levels and lower blood glucose levels, and they did not present with hyperinsulinemia or IR.
CONCLUSION
A better and stabilized mouse model simulating the pathophysiological defects of PCOS was induced by DHEA alone rather than by DHEA+HFD. The ABX intervention improved glucose metabolic disorders and hyperinsulinemia but aggravated the hyperandrogenism and lipid metabolic disorders of the PCOS mice. This study suggests that the gut microbiota plays an important role in the heterogeneous phenotypes of PCOS mouse models.
Topics: Female; Humans; Mice; Animals; Polycystic Ovary Syndrome; Hyperandrogenism; Diet, High-Fat; Gastrointestinal Microbiome; Insulin Resistance; Phenotype; Dehydroepiandrosterone; Lipids
PubMed: 36619569
DOI: 10.3389/fendo.2022.1030151