The steroid hormones are transported from their sites of biosynthesis to their target steroid hormones, and their transport is facilitated by a family of plasma transport proteins (see Table 1). All steroid hormones, except one, have their cognate plasma binding protein. The exception is aldosterone, which is believed to circulate as the free steroid in the plasma compartment. Although the five plasma transport proteins listed in Table 1 are all synthesized in the liver, they have no amino acid sequence homology. Also, there is no discernable sequence homology between the ligand-binding domains of the five plasma transport proteins, or the nuclear–cytosol receptor’s ligand-binding domain, or the substrate-binding domain of the P450 enzyme(s) that generated the steroid.
Table1. Plasma Transport Proteins for Steroids, Thyroxine, and Retinoid Hormones
In the plasma compartment, the steroid hormones move through the circulatory system bound to their partner transport protein. However, an important issue concerns the details of the mode of delivery of steroid hormones to their target cells. Since the “free” form of the steroid hormone is believed to be the form of steroid that moves across the outer plasma membrane of a target cell, it had been postulated that the steroid ligand bound to a plasma transport protein dissociates from its plasma transport protein and then diffuses first through the capillary wall and then through the outer wall membrane of target cells. However, as illustrated in Figure 1 it is apparent that the endothelial wall of capillaries contains fenestrations. Thus, it is also possible for the plasma steroid transport protein (with bound steroid hormone) to exit the capillary bed via a fenestration and move to be immediately adjacent to the outer cell membrane of the appropriate target cell for the steroid hormone in question. Here the steroid hormone will dissociate from the transport protein, diffuse through the plasma membrane, and then bind to an unoccupied partner steroid receptor.
Fig1. Examples of capillary wall fenestration. (A) Diagram representing the exit or entry processes of hormones via capillary orifices or fenestrations. (B) A fenestrated diaphragm in the endothelium of an adrenal cortex capillary. Note the eight, dark, wedge-shaped communicatory channels. The existence of fenestrations or pores in the capillary wall allows plasma steroid transport proteins to exit the circulatory system and approach the outer cell membrane of the target cell for the steroid hormone in question. [Adapted with permission from Figures 2 and 6 of Bearer, E., and Orci, L. (1985). Endothelial fenestral diaphragms: A quick-freeze, deep-etch study. J. Cell Biol 100, 418–428.]
