The concentration of steroid hormones in the circulation that are unbound to carrier proteins, such as Sex Hormone-Binding Globulin (SHBG) or albumin, and are therefore freely available to diffuse into target cells and exert their biological effects. Only the unbound fraction, often referred to as “free hormone,” is considered bioactive and capable of initiating endocrine signaling. This measurement provides a more accurate reflection of hormonal impact than total hormone levels.
Origin
This concept emerged from clinical endocrinology and pharmacology to explain the discrepancy between total measured hormone levels and the actual clinical manifestation of hormonal status. The understanding of transport proteins and their binding affinities was crucial in establishing the physiological relevance of the free hormone hypothesis. It is a cornerstone in the accurate diagnosis of androgen and estrogen deficiencies or excesses.
Mechanism
Steroid hormones, being lipid-soluble, require carrier proteins for transport in the aqueous blood plasma. SHBG and albumin bind a large percentage of these steroids, rendering them temporarily inactive. The mechanism of availability is governed by the equilibrium between bound and unbound fractions, which is highly sensitive to the concentration of carrier proteins and their binding capacity. Changes in SHBG levels, often influenced by liver function or insulin status, directly modulate the quantity of bioactive steroid available to tissues.
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