Mendel (1992) defined the free hormone hypothesis (FHH): the biological activity of a given hormone is ultimately affected by its unbound (free) rather than protein-bound concentration in the plasma1.  He believed this hypothesis is likely to be valid with respect to thyroid hormones, cortisol and hydroxylated metabolites of vitamin D.

Almost all circulating 25-OH Vitamin D in serum is bound to VDBP. In addition to VDBP, vitamin D metabolites can bind to albumin or circulate in a free form. Less than 1% of Total 25-OH Vitamin D circulates in the free, non-protein bound form. Chun and Hewison surmised that binding 25-OHVD to VDBP impairs the delivery of 25-OHVD to its target tissues, ultimately preventing metabolism into the active form, 1,25DHVD2.  Conversely, it is the unbound, free form that can cross the cell membrane and have a biological action.

September 21, 2015
hormone-image

What is the ‘free hormone hypothesis’?

Mendel (1992) defined the free hormone hypothesis (FHH): the biological activity of a given hormone is ultimately affected by its unbound (free) rather than protein-bound concentration […]
September 21, 2015
fhh

Evidence Supporting the FHH

Since most extra-renal tissues have not been shown to express megalin receptors, it has been suggested that these tissues are more directly impacted by free vitamin […]
July 7, 2015
vitamined

Vitamin D: To free or not to free?

Given the lipophilic nature of steroid hormones and sterols such as vitamin D, serum carrier proteins are required to ensure that they are delivered to target […]