Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role

Neulen

et al. 2020

Preprint

Background and objectives:Neuroactive steroids such as dehydroepiandrosterone (DHEA), estradiol (E2), and progesterone (P4) are associated with structural and functional changes in the central nervous system (CNS). Measurement of steroid levels in the CNS compartments, though restricted in accessibility, is essential for clinical evaluation. Consequently, there is only limited human data on the correlation and equilibrium for steroid levels between peripheral and central compartments. While some neuroactive steroids including DHEA and E2 have been reported to convey excitatory and proconvulsant properties, the opposite was demonstrated for progesterone. We aimed to elucidate the correlation between peripheral and central DHEA, E2, and P4 levels in women at term pregnancy.Subjects and Methods:CSF and serum samples of 27 healthy pregnant women (22-39 years) at term pregnancy were collected simultaneously under combined spinal and epidural anesthesia and used for DHEA, E2, and P4 ELISA.Results:All three neuroactive steroids were detected at markedly lower levels in CSF compared to their corresponding serum concentrations (decrease, mean ± SD, 97.66 ± 0.83 %).We found a strong correlation for DHEA between its serum and the corresponding CSF levels (r=0.65, p=0.003). While a significant but weak correlation (r=0.39, p=0.046) was detected for P4, serum and CSF levels of E2 (r=0.31, p=0.12) appeared not to correlate in the investigated cohort. DHEA serum concentration correlated significantly with both E2 (r=0.58, p=0.0016) and P4 in CSF (r=0.39, p=0.046). A strong correlation between the steroids DHEA and E2 measured in CSF was found (r=0.65, p=0.0002), while no substantial correlation between DHEA and P4 was evident in this compartment (r=0.34, p=0.085). Conclusions: Peripheral DHEA levels might serve as a valid predictor for central nervous levels of the neuroactive steroids DHEA and E2 in pregnant women.

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dehydroepiandrosterone (DHEA) Serum Levels Sufficiently Predict Cerebrospinal Fluid Levels of DHEA and Estradiol (E2) in Women at Term Pregnancy

Neulen

et al. 2020

Preprint

“…This enzyme represents a key step in the conversion of neuroactive steroids, such as progesterone (PROG) and testosterone (T) into their reduced metabolites, such as dihydroprogesterone (DHP), tetrahydroprogesterone (THP), and isopregnanolone in case of PROG and dihydrotestosterone (DHT), 5α-androstane-3α,17β-diol (3α-diol) and 5α-androstane-3β,17β-diol (3β-diol) in case of T. These neuroactive metabolites exert an important physiological control of the nervous functions by activating classical and non-classical steroid receptors [23,24]. In agreement, alterations of their levels have been reported in neurodegenerative and psychiatric disorders [25][26][27] as well as in PFS patients [14,21,22]. We have recently studied the PFS in a pre-clinical rat model, describing alterations of neuroactive steroid levels in brain areas [28] as well as depressivelike behavior coupled with cellular and molecular markers, such as a decrease in the neurogenesis and increased neuroinflammation and reactive gliosis, one month after drug treatment interruption [29].…”

Section: Introductionmentioning

confidence: 75%

Alterations of gut microbiota composition in post-finasteride patients: a pilot study

Borgo

Macandog

Diviccaro

et al. 2020

J Endocrinol Invest

Purpose Post-finasteride syndrome (PFS) has been reported in a subset of patients treated with finasteride (an inhibitor of the enzyme 5alpha-reductase) for androgenetic alopecia. These patients showed, despite the suspension of the treatment, a variety of persistent symptoms, like sexual dysfunction and cognitive and psychological disorders, including depression. A growing body of literature highlights the relevance of the gut microbiota-brain axis in human health and disease. For instance, alterations in gut microbiota composition have been reported in patients with major depressive disorder. Therefore, we have here analyzed the gut microbiota composition in PFS patients in comparison with a healthy cohort. Methods Fecal microbiota of 23 PFS patients was analyzed by 16S rRNA gene sequencing and compared with that reported in ten healthy male subjects. Results Sexual dysfunction, psychological and cognitive complaints, muscular problems, and physical alterations symptoms were reported in more than half of the PFS patients at the moment of sample collection. The quality sequence check revealed a low library depth for two fecal samples. Therefore, the gut microbiota analyses were conducted on 21 patients. The α-diversity was significantly lower in PFS group, showing a reduction of richness and diversity of gut microbiota structure. Moreover, when visualizing β-diversity, a clustering effect was found in the gut microbiota of a subset of PFS subjects, which was also characterized by a reduction in Faecalibacterium spp. and Ruminococcaceae UCG-005, while Alloprevotella and Odoribacter spp were increased compared to healthy control. Conclusion Gut microbiota population is altered in PFS patients, suggesting that it might represent a diagnostic marker and a possible therapeutic target for this syndrome.

“…Most studies suggest that women have greater frequency and lifetime risk than men. There is also mixed opinion concerning prevalence and incidence rates, and disease course [ 56 , 57 , 58 , 59 ]. Sex difference in the occurrence and distribution of Aβ plaques in the brain or CSF Aβ concentrations is unknown.…”

Section: Dysregulated Brain Steroidogenesis and Steroid Concentratmentioning

confidence: 99%

Steroids and Alzheimer’s Disease: Changes Associated with Pathology and Therapeutic Potential

Akwa

2020

IJMS

Alzheimer’s disease (AD) is a multifactorial age-related neurodegenerative disease that today has no effective treatment to prevent or slow its progression. Neuroactive steroids, including neurosteroids and sex steroids, have attracted attention as potential suitable candidates to alleviate AD pathology. Accumulating evidence shows that they exhibit pleiotropic neuroprotective properties that are relevant for AD. This review focuses on the relationship between selected neuroactive steroids and the main aspects of AD disease, pointing out contributions and gaps with reference to sex differences. We take into account the regulation of brain steroid concentrations associated with human AD pathology. Consideration is given to preclinical studies in AD models providing current knowledge on the neuroprotection offered by neuroactive (neuro)steroids on major AD pathogenic factors, such as amyloid-β (Aβ) and tau pathology, mitochondrial impairment, neuroinflammation, neurogenesis and memory loss. Stimulating endogenous steroid production opens a new steroid-based strategy to potentially overcome AD pathology. This article is part of a Special Issue entitled Steroids and the Nervous System.