Inertia of endocrine systems due to hormone binding to circulatory proteins.

ABSTRACT

It is often presumed that the main role of hormone binding to albumins and binding proteins (BPs) is to reduce oscillating levels of free hormone molecules and to transport steroid hormones. This paper is an attempt to define possible consequences of hormone molecules binding to carrier proteins in circulation. Binding to albumins and BPs prevents exact and quick control of hormone actions. Hormones without significant protein binding govern vital and fast acting regulatory mechanisms (blood glucose or calcium) in which any added inertia might be dangerous. In the presented model, the added inertia for a partially bound hormone (H) is defined as H(bound)/H(free). Values, calculated from the reported data, range from 0.4 for GH to more than 2000 for T(4). In comparison to albumins, high-affinity BPs make more stable reserve that would cover periods of low or no hormone secretion. At the same time, hormone molecules are taken away from the blood level control and thus might be considered sequestrated. For hormones without protein binding, the well-perfused areas of the body, or the areas with increased capillary permeability, would be more exposed, making an uneven distribution among target tissues. For the hormone that binds blood proteins, places of secretion and tissue perfusion become unimportant, since the hormone is being liberated anywhere in the circulation (i.e., for strongly bound IGFs, IGF binding proteins do not just stabilize proinsulin actions of IGF-1, but also make all parts of body to be under the same exposure to liberated IGFs, an important feature to promote a symmetrical bone growth). Estrogens are known to stimulate liver secretion of different BPs. A possible explanation is that in the follicular phase there is a small initial mass of granulosa cells, and it takes time to saturate free estrogen carriers, before the normal free hormone level can be reached and FSH secretion inhibited. Less inert peptide inhibin might suppress FSH before free estrogens reach the required level. Without inhibin suppression, an increased FSH level with an increased number of growing follicles can be expected. Estrogens increased production of BPs augments inertia of the estrogen loop and possibly modulates the FSH/estrogen negative feedback.