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The Journal of Steroid Biochemistry and... Jan 2015Approximately 20-30% of PCOS women demonstrate excess adrenal precursor androgen (APA) production, primarily using DHEAS as a marker of APA in general and more... (Review)
Review
Approximately 20-30% of PCOS women demonstrate excess adrenal precursor androgen (APA) production, primarily using DHEAS as a marker of APA in general and more specifically DHEA, synthesis. The role of APA excess in determining or causing PCOS is unclear, although observations in patients with inherited APA excess (e.g., patients with 21-hydroxylase deficient congenital classic or non-classic adrenal hyperplasia) demonstrate that APA excess can result in a PCOS-like phenotype. Inherited defects of the enzymes responsible for steroid biosynthesis, or defects in cortisol metabolism, account for only a very small fraction of women suffering from hyperandrogenism or APA excess. Rather, women with PCOS and APA excess appear to have a generalized exaggeration in adrenal steroidogenesis in response to ACTH stimulation, although they do not have an overt hypothalamic-pituitary-adrenal axis dysfunction. In general, extra-adrenal factors, including obesity, insulin and glucose levels, and ovarian secretions, play a limited role in the increased APA production observed in PCOS. Substantial heritabilities of APAs, particularly DHEAS, have been found in the general population and in women with PCOS; however, the handful of SNPs discovered to date account only for a small portion of the inheritance of these traits. Paradoxically, and as in men, elevated levels of DHEAS appear to be protective against cardiovascular risk in women, although the role of DHEAS in modulating this risk in women with PCOS remains unknown. In summary, the exact cause of APA excess in PCOS remains unclear, although it may reflect a generalized and inherited exaggeration in androgen biosynthesis of an inherited nature.
Topics: Androgens; Animals; Body Mass Index; Cardiovascular Diseases; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Hyperandrogenism; Phenotype; Polycystic Ovary Syndrome; Prevalence; Risk Factors; Steroids
PubMed: 25008465
DOI: 10.1016/j.jsbmb.2014.06.003 -
Vitamins and Hormones 2018
Topics: Animals; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Humans
PubMed: 30029739
DOI: 10.1016/S0083-6729(18)30062-1 -
Vitamins and Hormones 2018Dehydroepiandrosterone (DHEA)-SO of adrenal origin is the major C19 steroid in the serum. It is a precursor of intratumoral androgen biosynthesis in patients with... (Review)
Review
Dehydroepiandrosterone (DHEA)-SO of adrenal origin is the major C19 steroid in the serum. It is a precursor of intratumoral androgen biosynthesis in patients with advanced prostate cancer following chemical or surgical castration. DHEA is a product of the P450c17 (17α-hydroxylase-17,20-lyase) enzyme. Despite inhibition of P450c17 with new agents, e.g., Abiraterone acetate, Orterenol, and Galeterone, the level of enzyme inhibition rarely exceeds 90% leaving behind a significant depot for androgen biosynthesis within the tumor. For DHEA-SO to be utilized there is uptake by organic anion transporter polypeptides, deconjugation catalyzed by steroid sulfatase, and adaptive upregulation of prostate steroidogenic enzymes that will convert DHEA into either testosterone or dihydrotestosterone. The depot of DHEA-SO that remains after P450c17 inhibition and the adaptive responses that occur within the tumor to promote DHEA utilization contribute to mechanisms of drug resistance observed with P450c17 inhibitors. Knowledge of these mechanisms identify new targets for therapeutics that could be used to surmount drug resistance in prostate cancer.
Topics: Antineoplastic Agents; Dehydroepiandrosterone Sulfate; Delayed-Action Preparations; Gene Expression Regulation, Neoplastic; Humans; Male; Prostatic Neoplasms, Castration-Resistant; Steroid 17-alpha-Hydroxylase
PubMed: 30029732
DOI: 10.1016/bs.vh.2018.01.007 -
Best Practice & Research. Clinical... Jan 2015Although dehydroepiandrosterone (DHEA) and its sulphate ester dehydroepiandrosterone sulphate (DHEAS) are the most abundant steroid hormones in the human circulation,... (Review)
Review
Although dehydroepiandrosterone (DHEA) and its sulphate ester dehydroepiandrosterone sulphate (DHEAS) are the most abundant steroid hormones in the human circulation, its exact physiological role is not yet fully understood. In patients with adrenal insufficiency, secretion of DHEA is impaired, leading to decreased circulating DHEA and DHEAS levels, and to androgen deficiency in women. Replacement of DHEA in patients with adrenal insufficiency positively influence mood, sexuality and subjective health status. These effects are generally moderate and show high inter-individual variability. Limited evidence exists for immunomodulatory effects of DHEA. Although an increase of IGF-I levels has been documented, relevant effects on body composition, metabolic or cardiovascular parameters has not been observed in patients with adrenal insufficiency receiving DHEA. Larger-scale phase III studies are still lacking; therefore, initiation of DHEA replacement is decided on an individual basis, focussing on those patients with impaired well-being associated with signs and symptoms of androgen deficiency.
Topics: Adrenal Insufficiency; Androgens; Dehydroepiandrosterone; Health Status; Hormone Replacement Therapy; Humans; Sexual Behavior; Treatment Outcome
PubMed: 25617170
DOI: 10.1016/j.beem.2014.09.007 -
Climacteric : the Journal of the... Apr 2017Faced with the growing interest about the action of dehydroepiandrosterone (DHEA) and its benefits, as well as the negative impacts that sexual dysfunctions have on... (Review)
Review
OBJECTIVE
Faced with the growing interest about the action of dehydroepiandrosterone (DHEA) and its benefits, as well as the negative impacts that sexual dysfunctions have on people's quality of life, this systematic review was undertaken with the objective of evaluating the effect of DHEA use on aspects of sexual function.
METHOD
An electronic search was conducted in the databases of PubMed, ISI Web of Science and Virtual Health Library (VHL) combining the terms 'DHEA treatment' and 'DHEA use' with terms such as 'sexual dysfunction', 'sexual frequency' and 'libido'. No limits on time and language were imposed. Clinical studies were considered eligible where individuals for any reason made use of DHEA and if they had any aspect of sexual function assessed. Preclinical studies and systematic reviews were considered ineligible.
RESULTS
The search identified 183 references and 38 were considered eligible. DHEA improved aspects such as sexual interest, lubrication, pain, arousal, orgasm and sexual frequency. Its effect was better in populations with sexual dysfunction, especially in perimenopausal and postmenopausal women.
CONCLUSION
Considering the studies currently published, DHEA is effective in improving several aspects of sexual function, but this effect did not reach all the populations studied.
Topics: Dehydroepiandrosterone; Female; Humans; Libido; Middle Aged; Postmenopause; Quality of Life; Sexual Behavior; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological
PubMed: 28118059
DOI: 10.1080/13697137.2017.1279141 -
Psychiatria Danubina Mar 2016Neurosteroid dehydropiandrosterone (DHEA) and its sulphate (DHEAS) are reported to have modulatory effects on neuronal excitabillity and synaptic plasticity. DHEA and... (Review)
Review
Neurosteroid dehydropiandrosterone (DHEA) and its sulphate (DHEAS) are reported to have modulatory effects on neuronal excitabillity and synaptic plasticity. DHEA and DHEAS are synthesized in central and peripheral nervous system from cholesterol or steroidal precursors imported from peripheral sources. There is accumulating evidence that alterations in DHEA(S) levels may be involved in the pathophysiology of schizophrenia. The possible effects of DHEA(S) as augmentation therapy in schizophrenia, related to psychological and somatic aspects of this disease, are discussed.
Topics: Dehydroepiandrosterone; Humans; Neurotransmitter Agents; Schizophrenia
PubMed: 26938818
DOI: No ID Found -
Progress in Neurobiology Sep 2016Stroke and traumatic injuries of the brain and spinal cord are major public health issues. In the last few decades, hundreds of clinical trials with patients suffering... (Review)
Review
Stroke and traumatic injuries of the brain and spinal cord are major public health issues. In the last few decades, hundreds of clinical trials with patients suffering from these conditions have been done, however, most of them had not succeeded and there is still the need to develop more effective treatments for these conditions. Astrocytes play critical roles in the development, function and survival of neurons in the central nervous system. These cells are implicated in the pathophysiology and in the response to several neuropathological conditions and may represent potential cell targets for neuroprotective strategies. Progesterone and dehydroepiandrosterone (DHEA) are neuroactive steroids that modulate neuronal and astroglial function and have neuroprotective effects in different experimental models, being potential candidates to the development of new therapeutic approaches for brain and spinal cord injuries. The aim of this review is to discuss the role of astrocytes in the pathophysiology of brain and spinal cord injuries and how they could be modulated by progesterone and DHEA for the treatment of these conditions.
Topics: Animals; Astrocytes; Brain Injuries; Dehydroepiandrosterone; Humans; Neuroprotection; Progesterone; Spinal Cord Injuries
PubMed: 27048624
DOI: 10.1016/j.pneurobio.2016.03.010 -
Journal of Molecular Medicine (Berlin,... Jan 2020Dehydroepiandrosterone (DHEA), mostly present as its sulfated ester (DHEA-S), is an anabolic hormone that naturally declines with age. Furthermore, it is the most... (Review)
Review
Dehydroepiandrosterone (DHEA), mostly present as its sulfated ester (DHEA-S), is an anabolic hormone that naturally declines with age. Furthermore, it is the most abundant androgen and estrogen precursor in humans. Low plasma levels of DHEA have been strongly associated with obesity, insulin resistance, dyslipidemia, and high blood pressure, increasing the risk of cardiovascular disease. In this respect, DHEA could be regarded as a promising agent against metabolic syndrome (MetS) in postmenopausal women, since several age-related metabolic diseases are reported during aging. There are plenty of experimental evidences showing beneficial effects after DHEA therapy on carbohydrate and lipid metabolism, as well as cardiovascular health. However, its potential as a therapeutic agent appears to attract controversy, due to the lack of effects on some symptoms related to MetS. In this review, we examine the available literature regarding the impact of DHEA therapy on adiposity, glucose metabolism, and the cardiovascular system in the postmenopausal period. Both clinical studies and in vitro and in vivo experimental models were selected, and where possible, the main cellular mechanisms involved in DHEA therapy were discussed. Schematic representation showing some of the general effects observed after administration DHEA therapy on target tissues of energy metabolism and the cardiovascular system. ↑ represents an increase, ↓ represents a decrease, - represents a worsening and ↔ represents no change after DHEA therapy.
Topics: Aged; Aged, 80 and over; Aging; Animals; Cardiovascular Diseases; Cardiovascular System; Dehydroepiandrosterone; Female; Humans; Insulin Resistance; Lipid Metabolism; Male; Metabolic Syndrome; Middle Aged; Obesity; Postmenopause
PubMed: 31713639
DOI: 10.1007/s00109-019-01842-5 -
Vitamins and Hormones 2018Dehydroepiandrosterone (DHEA) is a precursor of sex steroid hormones and is converted to testosterone and estradiol. Normally, androgens and estrogens produced adrenal... (Review)
Review
Dehydroepiandrosterone (DHEA) is a precursor of sex steroid hormones and is converted to testosterone and estradiol. Normally, androgens and estrogens produced adrenal cortex, testis, and ovary; however, recent studies revealed androgens and estrogens are synthesized by peripheral tissues such as brain, skin, liver, kidney, bone, etc. We found skeletal muscles are also capable of synthesizing androgens and estrogens from DHEA. Circulating DHEA provides substrates required for conversion into potent androgens and estrogens in peripheral tissues. Sex steroid hormone administration has important roles: one is that the enhancement of protein synthesis and anabolism, resulting in muscle growth and increased muscle strength. The other is improvement of hyperglycemia through the activation of glucose signaling pathway in skeletal muscle as well as acceleration of muscle lipid metabolism that increase peroxisome proliferator-activated receptor alpha (PPARα) and PPAR delta (PPARδ). We introduce the effect of DHEA and sex steroid hormones administration on muscle glucose and lipid metabolisms as well as the effect of sex steroid hormone on the muscle hypertrophy.
Topics: Animals; Dehydroepiandrosterone; Glucose; Humans; Lipid Metabolism; Muscle, Skeletal; Steroids
PubMed: 30029727
DOI: 10.1016/bs.vh.2018.03.002 -
Organic & Biomolecular Chemistry Apr 2023Menarandroside A, which bears a 12α-hydroxypregnenolone steroid backbone, was isolated from the plant, . Treatment of extracts from this plant containing menarandroside...
Menarandroside A, which bears a 12α-hydroxypregnenolone steroid backbone, was isolated from the plant, . Treatment of extracts from this plant containing menarandroside A against secretin tumor cell line (STC-1) intestinal cells, resulted in an increased secretion of glucagon-like peptide 1 (GLP-1), a peptide that plays a role in the regulation of blood sugar levels. Increase in GLP-1 is beneficial for the treatment of type 2 diabetes. We disclose the synthesis of menarandroside A from dehydroepiandrosterone (DHEA). Key features of this synthesis include: (i) Wittig reaction of the C17-ketone of a 12-oxygenated DHEA derivative to introduce the C17-acetyl moiety, and (ii) the stereoselective reduction of a C12-keto intermediate bearing an sp-center at C17 to yield the C12α-hydroxy group. In addition, an oxidation of a methyl enol ether derivative to an α-hydroxy methyl ester using tetrapropylammonium perruthenate (TPAP) and -methyl-morpholine--oxide (NMO) was discovered.
Topics: Humans; Diabetes Mellitus, Type 2; Steroids; Glucagon-Like Peptide 1; Oxidation-Reduction; Dehydroepiandrosterone
PubMed: 36950968
DOI: 10.1039/d3ob00054k