-
Proceedings. Biological Sciences Sep 2022Coordinating physiological and behavioural processes across the annual cycle is essential in enabling individuals to maximize fitness. While the mechanisms underlying...
Coordinating physiological and behavioural processes across the annual cycle is essential in enabling individuals to maximize fitness. While the mechanisms underlying seasonal reproduction and its associated behaviours are well characterized, fewer studies have examined the hormonal basis of non-reproductive social behaviours (e.g. aggression) on a seasonal time scale. Our previous work suggests that the pineal hormone melatonin facilitates a 'seasonal switch' in neuroendocrine regulation of aggression in male and female Siberian hamsters (), specifically by acting on the adrenal glands to increase the production of the androgen dehydroepiandrosterone (DHEA) during the short-day (SD) photoperiods of the non-breeding season. Here, we provide evidence that the activity of 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD), a key enzyme within the steroidogenic pathway that mediates DHEA synthesis and metabolism, varies in a sex-specific and melatonin-dependent manner. Although both male and female hamsters displayed increased aggression in response to SDs and SD-like melatonin, only males showed an increase in adrenal 3β-HSD activity. Conversely, SD and melatonin-treated females exhibited reductions in both adrenal and neural 3β-HSD activity. Collectively, these results suggest a potential role for 3β-HSD in modulating non-breeding aggression and, more broadly, demonstrate how distinct neuroendocrine mechanisms may underlie the same behavioural phenotype in males and females.
Topics: Aggression; Animals; Cricetinae; Dehydroepiandrosterone; Female; Male; Melatonin; Phodopus; Seasons
PubMed: 36100021
DOI: 10.1098/rspb.2022.0668 -
Fertility and Sterility Jul 1998To determine the effect of administering 6 months of oral postmenopausal DHEA therapy on serum DHEA, DHEAS, and T levels and on physiologic endpoints including... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
OBJECTIVE
To determine the effect of administering 6 months of oral postmenopausal DHEA therapy on serum DHEA, DHEAS, and T levels and on physiologic endpoints including lipoproteins and insulin-like growth factor-I (IGF-I).
DESIGN
Randomized, double-blind, parallel trial.
SETTING
Academic referral practice.
PATIENT(S)
Thirteen normal-weight or overweight, healthy, nonsmoking, postmenopausal women.
INTERVENTION(S)
Administration of oral micronized DHEA (25 mg/d).
MAIN OUTCOME MEASURE(S)
Monthly fasting 23 hours postdose levels of serum DHEA, DHEAS, T, lipoproteins, IGF-I, IGF binding protein-3 (IGFBP-3), and liver function tests. Morphometric indices by dual-energy x-ray absorptiometry scan (percent body fat; lean body mass), immune indices, and insulin sensitivity.
RESULT(S)
Levels of DHEA, DHEAS, and T all rose into premenopausal ranges, but after 6 months, levels of DHEA and T did not differ from baseline or placebo. At 3 months, the ratio of IGF-I to IGFBP-3 rose by 36.1% +/- 12.7%, but it fell to placebo values by 6 months. High-density lipoprotein and apolipoprotein A1 levels declined.
CONCLUSION(S)
Patients appeared to tolerate 6 months of DHEA therapy well. Given the small study size, no statistically significant differences in morphometric indices, immune indices, or insulin-sensitizing properties were observed, but significant attenuation of bioavailability occurred. Supplementation with DHEA increased IGF-I/IGFBP-3 levels at 3 months and decreased high-density lipoprotein and apolipoprotein A1 levels at 6 months.
Topics: Androgens; Body Composition; Dehydroepiandrosterone; Double-Blind Method; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Lipoproteins, HDL; Middle Aged; Postmenopause; Time Factors
PubMed: 9660430
DOI: 10.1016/s0015-0282(98)00121-6 -
Psychoneuroendocrinology Oct 2017Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been suggested as a potential mechanism linking sleep and cardiometabolic disorders. However, the...
Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been suggested as a potential mechanism linking sleep and cardiometabolic disorders. However, the associations of two primary outputs of the HPA axis, cortisol and its antagonist dehydroepiandrosterone (DHEA), with sleep are less well studied. In the Nurses' Health Study II, 233 postmenopausal women provided five timed saliva samples over one day (immediately upon waking, 45min, 4h, and 10h after waking, and prior to going to sleep) to measure cortisol and DHEA. Of these, 209 completed assessment of their habitual sleep patterns using the Pittsburgh Sleep Quality Index (PSQI). We used piecewise linear mixed models to compare cross-sectional associations of slopes reflecting diurnal cortisol and DHEA rhythms with overall sleep quality and with seven sub-components. Overall, we observed no differences in the diurnal patterns of cortisol or DHEA between good versus poor sleepers as assessed by the global PSQI score. However, longer sleep latency was associated with significantly reduced cortisol awakening rise (p=0.02). Poorer subjective sleep quality (p=0.02), shorter sleep duration (p=0.02), and lower sleep efficiency (p=0.03) were associated with slower rate of cortisol decline later in the day. Women reporting daytime dysfunction had a sharper cortisol decline early in the day (p=0.03) but a flattened decline later in the day (p=0.01). The differences in diurnal patterns of DHEA between good versus poor sleepers, though less pronounced, were similar in direction to those of cortisol. Self-reported sleep duration, efficiency, latency and daytime dysfunction were associated with altered diurnal rhythms of cortisol and, to a lesser extent, DHEA. These findings provide support for the interplay between sleep and the HPA axis that may contribute to cardiometabolic disease.
Topics: Aged; Circadian Rhythm; Cross-Sectional Studies; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Pituitary-Adrenal System; Postmenopause; Saliva; Sleep; Time Factors; Wakefulness
PubMed: 28738312
DOI: 10.1016/j.psyneuen.2017.07.484 -
Journal of Lipid Research Dec 2009Pregnenolone (PREG) and dehydroepiandrosterone (DHEA), and their respective sulfated forms PREGS and DHEAS, were among the first steroids to be identified in rodent...
Pregnenolone (PREG) and dehydroepiandrosterone (DHEA), and their respective sulfated forms PREGS and DHEAS, were among the first steroids to be identified in rodent brain. However, unreliable steroid isolation and solvolysis procedures resulted in errors, particularly in the case of brain steroid sulfates analyzed by radioimmunology or GC-MS of liberated free steroids. By using a solid-phase extraction recycling/elution procedure, allowing the strict separation of sulfated, free, and fatty acid esters of PREG and DHEA, PREGS and DHEAS, unlike free PREG, were not detected in rat and mouse brain and plasma. Conversely, considerable amounts of PREG and DHEA were released from unknown precursor(s) present in the lipoidal fraction, distinct from fatty acid ester conjugates. Chromatographic and mass spectrometric studies of the nature of the precursor(s) showed that autoxidation of brain cholesterol (CHOL) was responsible for the release of PREG and DHEA from the lipoidal fraction. When inappropriate protocols were used, CHOL was also the precursor of PREG and DHEA obtained from the fraction assumed to contain sulfated steroids. In contrast, free PREG was definitely confirmed as an endogenous steroid in rat brain. Our study shows that an early removal of CHOL from brain extracts coupled to well-validated extraction and fractionation procedures are prerequisites for reliable measurements of free and conjugated PREG and DHEA by GC-MS or other indirect methods.
Topics: Animals; Brain; Brain Chemistry; Cholesterol; Dehydroepiandrosterone; Male; Mice; Oxidation-Reduction; Pregnenolone; Rats; Rats, Sprague-Dawley
PubMed: 19506304
DOI: 10.1194/jlr.M900162-JLR200 -
Singapore Medical Journal Jul 2006Specific endocrine changes occur with the ageing process. The last decade has witnessed significant progress in the basic and clinical science of ageing, thereby... (Review)
Review
Specific endocrine changes occur with the ageing process. The last decade has witnessed significant progress in the basic and clinical science of ageing, thereby rejuvenating the interest in anti-ageing medicine, especially that of hormone replacement, by medical professionals and the lay public. However, endocrine manipulation as a therapeutic strategy for ageing is still evolving as continuing research attempts to answer the many questions of what it can achieve at the risk of incurring unknown long-term adverse effects. The current day doctor is confronted with a host of options, and will benefit from a synopsis of the latest evidence before making the most appropriate decision for aged patients seeking hormonal replacement therapy as a means to counter the effects of ageing. This review aims to give a rapid overview of the endocrine profile of geriatric population and the studies on the more controversial hormonal replacement therapies for the aged.
Topics: Aged; Aging; Dehydroepiandrosterone; Endocrine System; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Insulin-Like Growth Factor I; Melatonin; Testosterone
PubMed: 16810426
DOI: No ID Found -
Women's Health (London, England) Jan 2011Hypoactive Sexual Desire Disorder (HSDD) is the most common female sexual dysfunction. The diagnosis of HSDD requires the existence of personal distress or interpersonal... (Review)
Review
Hypoactive Sexual Desire Disorder (HSDD) is the most common female sexual dysfunction. The diagnosis of HSDD requires the existence of personal distress or interpersonal difficulties associated with low sexual desire, that cannot be explained by any other psychiatric affection and that is not exclusively due to a disease or substance. HSDD can have a serious effect on emotional wellbeing and interpersonal relationships, and it occurs in premenopausal and postmenopausal women. The Decreased Sexual Desire Screener is a shortened diagnostic method designed to help doctors who are not specialized in female sexual dysfunction to diagnose acquired HSDD in women. There is evidence that treatment with androgens or with estrogens is effective in HSDD; however, important unanswered questions still exist. Presently, new therapeutic strategies to combat HSDD are being researched, including novel methods of testosterone provision and drugs that act upon the CNS.
Topics: Adult; Aged; Androgens; Dehydroepiandrosterone; Female; Hormone Replacement Therapy; Humans; Middle Aged; Sexual Dysfunctions, Psychological; Testosterone; Young Adult
PubMed: 21175394
DOI: 10.2217/whe.10.81 -
BMJ Open Jul 2021The improvements in short-term outcome after severe trauma achieved through early resuscitation and acute care can be offset over the following weeks by an acute... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The improvements in short-term outcome after severe trauma achieved through early resuscitation and acute care can be offset over the following weeks by an acute systemic inflammatory response with immuneparesis leading to infection, multiorgan dysfunction/multiorgan failure (MOF) and death. Serum levels of the androgen precursor dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, steroids with immune-enhancing activity, are low after traumatic injury at a time when patients are catabolic and immunosuppressed. Addressing this deficit and restoring the DHEA(S) ratio to cortisol may provide a range of physiological benefits, including immune modulatory effects.
OBJECTIVE
Our primary objective is to establish a dose suitable for DHEA supplementation in patients after acute trauma to raise circulating DHEA levels to at least 15 nmol/L. Secondary objectives are to assess if DHEA supplementation has any effect on neutrophil function, metabolic and cytokine profiles and which route of administration (oral vs sublingual) is more effective in restoring circulating levels of DHEA, DHEAS and downstream androgens.
METHODS AND ANALYSIS
A prospective, phase II, single-centre, cross-sectional, randomised study investigating Dehydroepiandrosterone supplementation and its profile in trauma, with a planned recruitment between April 2019 and July 2021, that will investigate DHEA supplementation and its effect on serum DHEA, DHEAS and downstream androgens in trauma. A maximum of 270 patients will receive sublingual or oral DHEA at 50, 100 or 200 mg daily over 3 days. Females aged ≥50 years with neck of femur fracture and male and female major trauma patients, aged 16-50 years with an injury severity score ≥16, will be recruited.
ETHICS AND DISSEMINATION
This protocol was approved by the West Midlands - Coventry and Warwickshire Research Ethics Committee (Reference 18/WM/0102) on 8 June 2018. Results will be disseminated via peer-reviewed publications and presented at national and international conferences.
TRIAL REGISTRATION
This trial is registered with the European Medicines Agency (EudraCT: 2016-004250-15) and ISRCTN (12961998). It has also been adopted on the National Institute of Health Research portfolio (CPMS ID:38158).
TRIAL PROGRESSION
The study recruited its first patient on 2 April 2019 and held its first data monitoring committee on 8 November 2019. DHEA dosing has increased to 100 mg in both male cohorts and remains on 50 mg in across all female groups.
Topics: Cross-Sectional Studies; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dietary Supplements; Female; Humans; Male; Prospective Studies
PubMed: 34312190
DOI: 10.1136/bmjopen-2020-040823 -
Drug Metabolism Reviews 2006Dehydroepiandrosterone has been thought to have physiological functions other than as an androgen precursor. The previous studies performed have demonstrated a number of... (Review)
Review
Dehydroepiandrosterone has been thought to have physiological functions other than as an androgen precursor. The previous studies performed have demonstrated a number of biological effects in rodents, such as amelioration of disease in diabetic, chemical carcinogenesis, and obesity models. To date, activation of the peroxisome proliferators activated receptor alpha, pregnane X receptor, and estrogen receptor by DHEA and its metabolites have been demonstrated. Several membrane-associated receptors have also been elucidated leading to additional mechanisms by which DHEA may exert its biological effects. This review will provide an overview of the receptor multiplicity involved in the biological activity of this sterol.
Topics: Animals; Dehydroepiandrosterone; Humans; PPAR gamma; Pregnane X Receptor; Receptors, Cytoplasmic and Nuclear; Receptors, Estrogen; Receptors, Steroid
PubMed: 16684650
DOI: 10.1080/03602530600569877 -
Biological Chemistry Jul 2004The new scientific field of nutrigenomics utilizes genomic tools, like microarrays, to analyze metabolic adaptations induced by variations in nutritional status. Here we... (Review)
Review
The new scientific field of nutrigenomics utilizes genomic tools, like microarrays, to analyze metabolic adaptations induced by variations in nutritional status. Here we describe how transcriptional regulation patterns caused by nutritional changes can be identified using gene expression profiling. This includes technical remarks on microarray analysis and data processing, as well as giving biological meaning to statistically solid data. We highlight our recent findings of transcriptional regulation of genes representing specific signaling and metabolic pathways in mouse liver under starvation. The results show strong correlations to previously identified responses to caloric restriction, which can be linked to lifespan extension.
Topics: Amino Acids; Animals; Dehydroepiandrosterone; Fatty Acids; Gene Expression Profiling; Genomics; Insulin; Mice; Nutritional Physiological Phenomena; Oligonucleotide Array Sequence Analysis; Signal Transduction
PubMed: 15318807
DOI: 10.1515/BC.2004.073 -
Journal of Neuroendocrinology Dec 2016Dehydroepiandrosterone (DHEA) is a testosterone/oestrogen precursor and known modulator of vertebrate aggression. Male song sparrows (Melospiza melodia morphna) show...
Dehydroepiandrosterone (DHEA) is a testosterone/oestrogen precursor and known modulator of vertebrate aggression. Male song sparrows (Melospiza melodia morphna) show high aggression during breeding and nonbreeding life-history stages when circulating DHEA levels are high, and low aggression during molt when DHEA levels are low. We previously showed that androgen receptor and aromatase mRNA expression are higher during breeding and/or nonbreeding in brain regions associated with reproductive and aggressive behaviour, although the potential role of DHEA in mediating these seasonal changes remained unclear. In the present study, nonbreeding male song sparrows were captured and held in the laboratory under short days (8 : 16 h light/dark cycle) and implanted with s.c. DHEA-filled or empty (control) implants for 14 days. DHEA implants increased aggression in a laboratory-based simulated territorial intrusion. Brains of DHEA-implanted birds showed higher aromatase mRNA expression in the preoptic area (POA) and higher androgen receptor mRNA expression in the periventricular nucleus of the medial striatum (pvMSt) and ventromedial nucleus of the hypothalamus. The DHEA-induced increases in aromatase expression in the POA and androgen receptor expression in the pvMSt are consistent with previously reported seasonal increases in these markers associated with naturally elevated DHEA levels. This suggests that DHEA facilitates seasonal increases in aggression in nonbreeding male song sparrows by up-regulating steroid signalling/synthesis machinery in a brain region-specific fashion.
Topics: Aggression; Animals; Aromatase; Avian Proteins; Brain; Dehydroepiandrosterone; Male; RNA, Messenger; Receptors, Androgen; Sparrows
PubMed: 27805753
DOI: 10.1111/jne.12443