2 research outputs found
Activin is produced by rat Sertoli cells in vitro and can act as an autocrine regulator of Sertoli cell function
Regulation of androgen receptor (AR) mRNA expression was studied in
Sertoli cells and peritubular myoid cells isolated from immature rat
testis, and in the lymph node carcinoma cell line derived from a human
prostate (LNCaP). Addition of dibutyryl-cyclic AMP (dbcAMP) to Sertoli
cell cultures resulted in a rapid transient decrease in AR mRNA expression
(5 h), which was followed by a gradual increase in AR mRNA expression
(24-72 h). This effect of dbcAMP mimicked follicle-stimulating hormone
(FSH) action. In peritubular myoid cells, there was only a moderate but
prolonged decrease during incubation in the presence of dbcAMP, and in
LNCaP cells no effect of dbcAMP on AR mRNA expression was observed. When
Sertoli cells or peritubular myoid cells were cultured in the presence of
androgens, AR mRNA expression in these cell types did not change. This is
in contrast to LNCaP cells, that showed a marked reduction of AR mRNA
expression during androgen treatment. In the present experiments,
transcriptional regulation of AR gene expression in Sertoli cells and
LNCaP cells was also examined. Freshly isolated Sertoli cell clusters were
transfected with a series of luciferase reporter gene constructs, driven
by the AR promoter. It was found that addition of dbcAMP to the
transfected Sertoli cells resulted in a small but consistent increase in
reporter gene expression (which was interpreted as resulting from AR
promoter activity); a construct that only contained the AR 5' untranslated
region of the cDNA sequence did not show such a regulation. The same
constructs, transfected into LNCaP cells, did not show any transcriptional
down-regulation when the synthetic androgen R1881 was added to the cell
cultures. A nuclear transcription elongation experiment (run-on), however,
demonstrated that androgen-induced AR mRNA down-regulation in LNCaP cells
resulted from an inhibition of AR gene transcription. The present results
indicate that in Sertoli cells and LNCaP cells, hormonal effects on AR
gene transcription play a role in regulation of AR expression. However, AR
gene transcription in these cells is differentially regulated
Plasma amyloid-β levels, cerebral atrophy and risk of dementia: A population-based study
Background: Plasma amyloid-β (Aβ) levels are increasingly studied as a potential accessible marker of cognitive impairment and dementia. However, it remains underexplored whether plasma Aβ levels including the novel Aβ peptide 1-38 (Aβ1-38) relate to preclinical markers of neurodegeneration and risk of dementia. We investigated the association of plasma Aβ1-38, Aβ1-40, and Aβ1-42 levels with imaging markers of neurodegeneration and risk of dementia in a prospective population-based study. Methods: We analyzed plasma Aβ levels in 458 individuals from the Rotterdam Study. Brain volumes, including gray matter, white matter, and hippocampus, were computed on the basis of 1.5-T magnetic resonance imaging (MRI). Dementia and its subtypes were defined on the basis of internationally accepted criteria. Results: A total of 458 individuals (mean age, 67.8 ± 7.7 yr; 232 [50.7%] women) with baseline MRI scans and incident dementia were included. The mean ± SD values of Aβ1-38, Aβ1-40, and Aβ1-42 (in pg/ml) were 19.4 ± 4.3, 186.1 ± 35.9, and 56.3 ± 6.2, respectively, at baseline. Lower plasma Aβ1-42 levels were associated with smaller hippocampal volume (mean difference in hippocampal volume per SD decrease in Aβ1-42 levels, - 0.13; 95% CI, - 0.23 to - 0.04; p = 0.007). After a mean follow-up of 14.8 years (SD, 4.9; range, 4.1-23.5 yr), 79 persons developed dementia, 64 of whom were diagnosed with Alzheimer's disease (AD). Lower levels of Aβ1-38 and Aβ1-42 were associated with increased risk of dementia, specifically AD (HR for AD per SD decrease in Aβ1-38 levels, 1.39; 95% CI, 1.00-2.16; HR for AD per SD decrease in Aβ1-42 levels, 1.35; 95% CI, 1.05-1.75) after adjustment for age, sex, education, cardiovascular risk factors, apolipoprotein E ϵ4 allele carrier status, and other Aβ isoforms. Conclusions: Our results show that lower plasma Aβ levels were associated with risk of dementia and incident AD. Moreover, lower plasma Aβ1-42 levels were related to smaller hippocampal volume. These results suggest that plasma Aβ1-38 and Aβ1-42 maybe useful biomarkers for identification of individuals at risk of dementia