Some Hormones Have Plasma Transport Proteins
المؤلف:
Peter J. Kennelly, Kathleen M. Botham, Owen P. McGuinness, Victor W. Rodwell, P. Anthony Weil
المصدر:
Harpers Illustrated Biochemistry
الجزء والصفحة:
32nd edition.p506-507
2025-11-16
45
The class I hormones are hydrophobic in chemical nature and thus are not very soluble in plasma. These hormones, principally the steroids and thyroid hormones, have specialized plasma transport proteins that serve several purposes. First, these proteins circumvent the solubility problem and thereby deliver the hormone to the target cell. They also provide a circulating reservoir of the hormone that can be substantial, as in the case of the thyroid hormones. Hormones, when bound to the transport proteins, cannot be metabolized, thereby prolonging their plasma half-life (t½ ). The binding affinity of a given hormone to its transporter determines the bound versus free ratio of the hormone. This is important because only the free form of a hormone is biologically active. In general, the concentration of free hormone in plasma is very low, in the range of 10−15 to 10−9 mol/L. It is important to distinguish between plasma transport proteins and hormone receptors. Both bind hormones but with very different characteristics (Table 1).
Table1. Comparison of Receptors With Transport Proteins
The hydrophilic hormones—generally class II and of peptide structure—are freely soluble in plasma and do not require transport proteins. Hormones such as insulin, growth hormone, ACTH, and TSH circulate in the free, active form and have very short plasma half-lives. A notable exception is IGF-I, which is transported bound to members of a family of binding proteins.
Thyroid Hormones Are Transported by Thyroid-Binding Globulin
Many of the principles discussed above are illustrated in a discussion of thyroid-binding proteins. One-half to two-thirds of T4 and T3 in the body is in an extrathyroidal reservoir. Most of this circulates in bound form, that is, bound to a specific binding protein, thyroxine-binding globulin (TBG). TBG, a glycoprotein with a molecular mass of 50 kDa, binds T4 and T3 and has the capacity to bind 20 μg/dL of plasma. Under nor mal circumstances, TBG binds—noncovalently—nearly all of the T4 and T3 in plasma, and it binds T4 with greater affinity than T3 (Table2). The plasma half-life of T4 is correspondingly four to five times that of T3. The small, unbound (free) fraction is responsible for the biologic activity. Thus, in spite of the great difference in total amount, the free fraction of T3 approximates that of T4 , and given that T3 is intrinsically more active than T4 , most biologic activity is attributed to T3 . TBG does not bind any other hormones.
Table2. Comparison of T4 and T3 in Plasma
Glucocorticoids Are Transported by Corticosteroid-Binding Globulin
Hydrocortisone (cortisol) also circulates in plasma in protein bound and free forms. The main plasma binding protein is an α-globulin called transcortin, or corticosteroid-binding globulin (CBG). CBG is produced in the liver, and its syn thesis, like that of TBG, is increased by estrogens. CBG binds most of the hormone when plasma cortisol levels are within the normal range; much smaller amounts of cortisol are bound to albumin. The affinity of binding helps determine the biologic half-lives of various glucocorticoids. Cortisol binds tightly to CBG and has a t½ of 1.5 to 2 hours, while corticosterone, which binds less tightly, has a t½ of less than 1 hour (Table 3). The unbound (free) cortisol constitutes ~8% of the total and represents the biologically active fraction. Binding to CBG is not restricted to glucocorticoids. Deoxy corticosterone and progesterone interact with CBG with sufficient affinity to compete for cortisol binding. Aldosterone, the most potent natural mineralocorticoid, does not have a specific plasma transport protein. Gonadal steroids bind very weakly to CBG (see Table 3).
Table3. Approximate Affinities of Steroids for Serum-Binding Proteins
Gonadal Steroids Are Transported by Sex Hormone–Binding Globulin
Most mammals, humans included, have a plasma β-globulin that binds testosterone with specificity, relatively high affinity, and limited capacity (see Table 3). This protein, usually called sex hormone–binding globulin (SHBG) or testosterone-estrogen binding globulin (TEBG), is produced in the liver. Its production is increased by estrogens (women have twice the serum concentration of SHBG as men), certain types of liver disease, and hyperthyroidism; it is decreased by androgens, advancing age, and hypothyroidism. Many of these conditions also affect the production of CBG and TBG. Since SHBG and albumin bind 97 to 99% of circulating testosterone, only a small fraction of the hormone in circulation is in the free (biologically active) form. The primary function of SHBG may be to restrict the free concentration of testosterone in the serum. Testosterone binds to SHBG with higher affinity than does estradiol (see Table 3). Therefore, a change in the level of SHBG causes a greater change in the free testosterone level than in the free estradiol level.
Estrogens are bound to SHBG and progestins to CBG. SHBG binds estradiol about five times less avidly than it binds testosterone or DHT, while progesterone and cortisol have little affinity for this protein (see Table 3). In contrast, progesterone and cortisol bind with nearly equal affinity to CBG, which in turn has little affinity for estradiol and even less for testosterone, DHT, or estrone.
These binding proteins also provide a circulating reservoir of hormone, and because of the relatively large binding capacity, they probably buffer against sudden changes in the plasma level. Because the metabolic clearance rates of these steroids are inversely related to the affinity of their binding to SHBG, estrone is cleared more rapidly than estradiol, which in turn is cleared more rapidly than testosterone or DHT.
الاكثر قراءة في الكيمياء الحيوية
اخر الاخبار
اخبار العتبة العباسية المقدسة
