18 research outputs found
Short-Term Fasting Attenuates Overall Steroid Hormone Biosynthesis in Healthy Young Women.
Context
Fasting is stressful for the human body. It is managed by metabolic adaptations maintaining energy homeostasis and involves steroid hormone biosynthesis, but the exact interplay between energy and steroid metabolism remains elusive. Women with polycystic ovary syndrome (PCOS) suffer from disturbed metabolism and androgen excess, while in women with anorexia nervosa, cortisol and androgen production are decreased. By contrast, starvation of steroidogenic cells shifts adrenal steroid biosynthesis toward enhanced androgen production.
Aim
This study investigated the effect of fasting on steroid production in healthy women.
Methods
Twenty healthy young women fasted for 48 hours; steroid profiles from plasma and urine samples were assessed at baseline, after 24 hours, and 48 hours by liquid and gas chromatography-mass spectrometry.
Results
Fasting did not change overall steroidogenesis, although it increased progestogen production and lowered relative mineralocorticoid, glucocorticoid, and androgen production. The largest decrease in urine metabolites was seen for β-cortol, dehydroepiandrosterone, and androstenediol; higher levels were found for pregnanediol in urine and progesterone and aldosterone in serum. Activity of 17α-hydroxylase/17,20-lyase (CYP17A1), essential for androgen biosynthesis, was decreased after fasting in healthy women as were 21-hydroxylase (CYP21A2) and 5α-reductase activities. By contrast, hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) activity for cortisol inactivation seemed to increase with fasting.
Conclusion
Significant changes in steroid metabolism occurred after 48 hours of fasting in healthy women. In contrast to metabolic changes seen at baseline in PCOS women compared to healthy women, and after starving of steroidogenic cells, no androgen excess was observed after short-term fasting in healthy young women
Loss of LGR4/GPR48 causes severe neonatal salt-wasting due to disrupted WNT signaling altering adrenal zonation.
Disorders of isolated mineralocorticoid deficiency causing potentially life-threatening salt-wasting crisis early in life have been associated with gene variants of aldosterone biosynthesis or resistance, but in some patients no such variants are found. WNT/β-catenin signaling is crucial for differentiation and maintenance of the aldosterone producing adrenal zona glomerulosa (zG). We describe a highly consanguineous family with multiple perinatal deaths or infants presenting at birth with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness. Whole exome sequencing revealed a homozygous splice variant in the R-SPONDIN receptor LGR4 gene (c.618-1G>C) regulating WNT signaling. The resulting transcripts affected protein function and stability, and resulted in loss of Wnt/β-catenin signaling in vitro. The impact of LGR4 inactivation was analyzed by adrenal cortex specific ablation of Lgr4, using Lgr4Flox/Flox mated with Sf1:Cre mice. Inactivation of Lgr4 within the adrenal cortex in the mouse model caused decreased WNT signaling, aberrant zonation with deficient zG and reduced aldosterone production. Thus, human LGR4 mutations establish a direct link between LGR4 inactivation and decreased canonical WNT signaling with abnormal zG differentiation and endocrine function. Therefore, variants in WNT signaling and its regulators should systematically be considered in familial hyperreninemic hypoaldosteronism
Estimation of reference curves for the urinary steroid metabolome in the first year of life in healthy children: Tracing the complexity of human postnatal steroidogenesis
Role of AMP-Activated Protein Kinase on Steroid Hormone Biosynthesis in Adrenal NCI-H295R Cells
Regulation of human androgen biosynthesis is poorly understood. However, detailed knowledge is needed to eventually solve disorders with androgen dysbalance. We showed that starvation growth conditions shift steroidogenesis of human adrenal NCI-H295R cells towards androgen production attributable to decreased HSD3B2 expression and activity and increased CYP17A1 phosphorylation and 17,20-lyase activity. Generally, starvation induces stress and energy deprivation that need to be counteracted to maintain proper cell functions. AMP-activated protein kinase (AMPK) is a master energy sensor that regulates cellular energy balance. AMPK regulates steroidogenesis in the gonad. Therefore, we investigated whether AMPK is also a regulator of adrenal steroidogenesis. We hypothesized that starvation uses AMPK signaling to enhance androgen production in NCI-H295R cells. We found that AMPK subunits are expressed in NCI-H295 cells, normal adrenal tissue and human as well as pig ovary cells. Starvation growth conditions decreased phosphorylation, but not activity of AMPK in NCI-H295 cells. In contrast, the AMPK activator 5-aminoimidazole-4-carboxamide (AICAR) increased AMPKα phosphorylation and increased CYP17A1-17,20 lyase activity. Compound C (an AMPK inhibitor), directly inhibited CYP17A1 activities and can therefore not be used for AMPK signaling studies in steroidogenesis. HSD3B2 activity was neither altered by AICAR nor compound C. Starvation did not affect mitochondrial respiratory chain function in NCI-H295R cells suggesting that there is no indirect energy effect on AMPK through this avenue. In summary, starvation-mediated increase of androgen production in NCI-H295 cells does not seem to be mediated by AMPK signaling. But AMPK activation can enhance androgen production through a specific increase in CYP17A1-17,20 lyase activity
Accelerated Early Childhood Growth Is Associated With the Development of Earlier Adrenarche and Puberty
Effects of 2-Year Physical Activity and Dietary Intervention on Adrenarchal and Pubertal Development: The PANIC Study
Androgen biosynthesis during minipuberty favors the backdoor pathway over the classic pathway: Insights into enzyme activities and steroid fluxes in healthy infants during the first year of life from the urinary steroid metabolome
A multicenter study on long-term outcomes in 56 males with 45,X/46,XY mosaicism
sem informação86126226255th Annual Meeting of the European Society for Paediatric Endocrinolog