Cortisone

3a, 11(3, 17a, 21-Tetrahydroxy-5/5-pregnan-20-one (Tetrabydro F)

3a, 11/3, 17a, 21-Tetrahydroxy-5a-pregnan-20-one

3a, 17a, 21-Trihydroxy-5a-pregnane-11, 20-dione CH3

3a, 17a, 21-TRIHYDROXY-5/3-PREGNANE-ll, 20-DIONE (Tetrabydro E)

3a, 11(3, 17a, 21-Tetrahydroxy-5/5-pregnan-20-one (Tetrabydro F)

3a, 11/3, 17a, 21-Tetrahydroxy-5a-pregnan-20-one

3a, 17a, 21-Trihydroxy-5a-pregnane-11, 20-dione CH3

3a, 17a, 21-TRIHYDROXY-5/3-PREGNANE-ll, 20-DIONE (Tetrabydro E)

Cortol

(20a- or 2Q/3-hydroxysteroid)

Allocortol (20a- or 20(3-hydroxy steroid)

Allocortolone (20a- or 20/3-hydroxysteroid)

Cortolone (20a- or 20(3-hydroxysteroid)

FIGURE 10-18 (Continued)

zinc finger of the the other receptor partner to produce this stabilized configuration. The interaction of the glucocorticoid homodimer with the double standard hormone-response element, based on X-ray diffraction data, is shown in Chapter 1.

The DNA-binding domain of the glucocorticoid receptor is shown in Figure 10-23. It consists of two Zn2+ fingers. The left (N-terminal) is the specific finger and contains the P (proximal) box of five amino acids that specify the DNA sequence to which the receptor will bind, while the right finger contains the D (distal) box

H2N'

ch3.

Metyrapone

Aminoglutethimide

FIGURE 10-19 Structures of metyrapone and aminoglutethimide.

of amino acids that specifies the spacing between the half-sites of the responsive element in terms of the receptor conformation that enables it to interact with the elements that are spaced appropriately. Other func-

Glucocorticoid + receptor Intracellular membrane

| phospholipids

Synthesis of lipocortin jPhospholipase A2[ or annexin 1 ^ jr^

Arachidonic acid

Represses inducible cyclooxygenase (Cox 2)

|lnhibits|

PG synthetase system

Prostaglandin

Release into cytosol or from cell

Inflammation

FIGURE 10-20 Action of glucocorticoids on the prostaglandin (PG) system.

Hormones, Second Edition

NFkB p65 stimulates transcription of IL-6 mRNA:

IL-6 gene promoter

IL-6 gene promoter

IL-6 (inflammatory cytokine) t

Inflammation

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