Feedback on a feedback loop: the hypothalamic-pituitary-gonadal axis.

Recent evidence indicates that transthyretin (TTR), the major transport protein for thyroxine [1] and retinol binding protein [2], plays important roles in amyloidβ (Aβ) metabolism. Transthyretin has been demonstrated to bind Aβ in vitro [3,4] and in vivo [5,6], colocalize in Aβ plaques and within neurons containing intracellular Aβ [7], and recent evidence suggests it might act as a transport protein for Aβ. Additionally, sAβPP-driven expression of transthyretin appears to be necessary for protection against Aβ induced neuronal death [7]. Therefore, the regulation of the expression of TTR may have important consequences for the deposition of Aβ in the brain. The findings of Tang and colleagues reported in JAD [8] that 17β-estradiol increases the gene expression of TTR in ovariectomized mice implicates reproductive hormones in the regulation of amyloid transport and deposition. While the sex steroids are undoubtedly important for brain function, they are controlled by a complex feedback loop that is made up of numerous other hormones including: gonadotropin releasing hormone (GnRH); the gonadotropinsluteinizing hormone