Transthyretin (TTR) is a protein mainly synthesized by the liver and choroid plexus (CP) of the brain. Besides its role as a carrier for thyroid hormones, TTR also sequesters the amyloid beta (Aβ) peptide impairing its deposition in nervous tissues, and its concentrations in the cerebrospinal fluid (CSF) appear to be inversely correlated with Alzheimers disease (AD) onset and progression. Abundant evidence suggests that the depletion of progesterone (PROG) at menopause is a significant risk factor for the development of AD in women, but the mechanisms involved are poorly understood. So, we examined the effects of PROG on TTR mRNA levels, in primary cultures of rat CP epithelial cells (CPEC) by Real Time PCR. We show that, PROG (100 nM) induced TTR transcription in these cells. The combination of mifepristone (RU486) with PROG in the treatment of CPEC abrogated the induction of TTR expression by PROG. Pre-treatment with ICI 182 780 and flutamide, specific oestrogen and androgen receptor antagonists, respectively, had no effect on TTR levels. These data suggest that the effects observed are due to PROG itself and not from downstream products from its metabolization, such as testosterone and estradiol, and indicates that TTR is up-regulated via a progesterone receptor (PR)-dependent pathway. Our results highlight the importance of PROG on the regulation of TTR, which may be involved in the neuroprotective role of PROG in AD described in the literature.
25 - 29 Apr 2009
European Society of Endocrinology