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Endocrine Abstracts (2015) 37 GP18.02 | DOI: 10.1530/endoabs.37.GP.18.02

1Institute of Endocrinology, Prague, Czech Republic; 2Thomayer Hospital, Prague, Czech Republic; 3Faculty of Humanities, Charles University, Prague, Czech Republic.


Background and aims: Neuroactive steroids and their metabolites play an important regulatory role in the nervous system affecting the neuronal plasticity, stress response, learning, and memory. The aim of the study was to compare the steroid metabolome in AD patients and controls.

Materials and methods: The study comprised of 48 AD patients (30 women and 18 men; age 73.8±9.54 years) and 33 matched controls (22 women and 11 men; age 68.2±5.94 years).

All subjects underwent neuropsychological examination and magnetic resonance imaging of the brain. Biochemical characterisation included examination of fasting glucose and lipid metabolism and the determination of extended spectrum of steroid hormones by GC–MS method (38 steroids and their sulfates). Statistical analyzes were performed using Statgraphics Centurion XVI 16.0.07 Software.

Results: AD patients had significantly higher insulin secretion (fasting insulin, HOMAF) and lower C peptide/insulin ratio compared to controls which indicates the decreased hepatic insulin extraction. AD patients had higher C21 steroids (5β-pregnane-3α, 20α-diol conjugate, women in addition pregnenolone, 16α-hydroxy-pregnenolone, 16a-hydroxy-progesterone, men in addition 16α-hydroxy-DHEA, and pregnanolone) and lower C19 steroids (5α-androstan-3β, 17β-diol conjugate, women in addition conjugates of androsterone, epiandrosterone, epietiocholanolon, and 5β-androstane-3β, 17β-diol) compared to controls. Neither in AD nor in controls a direct relationship of steroids with fasting glucose, insulin and HOMAR was found.

Conclusion: C21 steroid levels were consistently higher in AD, suggesting an increased activity of the zona fasciculata of adrenal gland. Conversely, levels of stable 5α/β reduced catabolites of C19 steroids, particularly their sulfates, are consistently reduced in AD (unlike insignificantly different unreduced androgenic precursors showing a diurnal variation). This indicates a decrease in the activity of the adrenal zona reticularis in AD. AD patients have higher levels of insulin in the periphery, however, the direct relationship between glucose tolerance and steroid metabolome was not confirmed.

Disclosure: This work was supported by grant IGA MH CR NT13543-4, MH CR 00023761.

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