Page 718 - Basic _ Clinical Pharmacology ( PDFDrive )

704 SECTION VII Endocrine Drugs

17 -Hydroxylase 17, 20-Lyase
(P450c17)
Acetate CH 3 CH 3
C O C O O
Cholesterol OH
(ACTH?)
NADPH
O 2
Pregnenolone 17-Hydroxy- Dehydroepi-
pregnenolone androsterone
HO HO HO
CH 3 CH 3
3 -Dehydrogenase
5 , 4 -Isomerase C O C O O
NAD + OH

Progesterone 17-Hydroxy- 4 -Androstene-
progesterone 3,17-dione
O O O
CH 2 OH CH 2 OH
21 -Hydroxylase
(P450c21) C O C O
OH
Testosterone

11-Deoxy- 11 -Deoxycortisol
corticosterone
O O
CH 2 OH CH 2 OH
11 -Hydroxylase C O C O Estradiol
(P450c11)
HO HO OH
CH 2 OH
C O Corticosterone Cortisol
CHO O O
HO

Aldosterone
O
Mineralocorticoid Glucocorticoid Androgen and
pathway pathway estrogen pathway

FIGURE 39–1 Outline of major pathways in adrenocortical hormone biosynthesis. The major secretory products are underlined. Pregneno-
lone is the major precursor of corticosterone and aldosterone, and 17-hydroxypregnenolone is the major precursor of cortisol. The enzymes and
cofactors for the reactions progressing down each column are shown on the left and across columns at the top of the figure. When a particular
enzyme is deficient, hormone production is blocked at the points indicated by the shaded bars. (Reproduced, with permission, from Ganong WF: Review
of Medical Physiology, 22nd ed. McGraw-Hill, 2005. Copyright © The McGraw-Hill Companies, Inc.)

THE NATURALLY OCCURRING system, which is very sensitive to negative feedback by the circu-
GLUCOCORTICOIDS; CORTISOL lating cortisol and exogenous (synthetic) glucocorticoids. Cortisol
is synthesized from cholesterol (as shown in Figure 39–1). The
(HYDROCORTISONE) mechanisms controlling its secretion are discussed in Chapter 37.
The rate of secretion follows a circadian rhythm (Figure 39–2)
Pharmacokinetics governed by pulses of ACTH that peak in the early morning hours
Cortisol (also called hydrocortisone, compound F) exerts a wide and after meals. In plasma, cortisol is bound to circulating pro-
range of physiologic effects, including regulation of intermediary teins. Corticosteroid-binding globulin (CBG), an α globulin
2
metabolism, cardiovascular function, growth, and immunity. Its synthesized by the liver, binds about 90% of the circulating hor-
synthesis and secretion are tightly regulated by the central nervous mone under normal circumstances. The remainder is free (about