Mineralocorticoid pathway

Cortisol synthesis requires three hydroxylases located in the fasciculata and reticularis zones of the adrenal cortex that act sequentially on the Cjy, C21, and Cjj positions. The first two reactions are rapid, while Cu hydroxylation is relatively slow. If the C, position is hydroxylated first, the action of 17a-hydroxylase is impeded and the mineralocorticoid pathway is followed (forming corti-... 

The glucocorticoid pathway is confined to the zona fasciculata of the adrenal cortex and it is catalyzed by the same CYP21 enzyme that is involved in the mineralocorticoid pathway in this zone along with CYPl IBl. The principal difference between the two pathways in the zona fasciculata is the initial substrate, and this explains... 

Women produce testosterone without testicles. (DUH ) A woman s sex hormones are produced starting at the adrenal glands and ovaries. Through a series of conversion enzyme pathways (chemicals that alter the molecular structure of other chemicals) their bodies synthesize the necessary sex, Glucocorticoid, and Mineralocorticoid steroids. 

FIGURE 29-1 Pathways of adrenal steroid biosynthesis. Cholesterol is the precursor for the three steroid hormone pathways. Note the similarity between the structures of the primary mineralocorticoid (aldosterone), the primary glucocorticoid (cortisol), and the sex hormones (testosterone, estradiol). See text for further discussion. 

Melanocortins. This is a generic name for the peptide hormones, melanotropin and corticotropin, (ACTH, adrenocorticotropic hormone), because both hormones are formed in the anterior pituitary gland from the same melanocortin precursor. Melanotropin controls melanocyte growth and pigmentation. Corticotropin stimulates the production of glucocorticoids and mineralocorticoids, such as aldosteron, in the adrenal cortex. The Melanocortin-pathway is somehow involved in the control of appetite and body weight. 

Hormone defects at key point in the hormonal pathways may give rise to a variety of syndromes in which there are increased or decreased mineralocorticoid, glucocorticoid and/or androgen-estrogen function. 

G-12) (G-13) 21-bydroxylase deficiency. This is the most common hereditary enzyme defect in steroid biosynthesis. There is decreased glucocorticoid and mineralocorticoid production, as the enzyme is common to both pathways. This leads to increased ACTH production, which in turn causes adrenal hyperplasia and increased pregnenolone production. This results in increased androgen production and virilization. Therapy consists in administering glucocorticoids. This decreases ACTH production by negative feedback. 

Mineralocorticoid refers to those steroids that regulate salt homeostasis (sodium conservation and potassium loss) and extracellular fluid volume.Aldosterone is the most potent naturally occurring mineralocorticoid and is synthesized exclusively in the zona glomerulosa region of the adrenal cortex. This zone uniquely contains the enzyme aldosterone synthase, an obligatory enzyme in the synthetic pathway to aldosterone. Other adrenocortical steroids that have mineralocorticoid properties with varying degrees of potency include DOC, 18-hydroxy-DOC, corticosterone,... 

The zona glomerulosa also secretes 18-hydroxy-corticosterone, a precursor steroid in the aldosterone biosynthetic pathway. This steroid also has mineralocorticoid properties, but is usually present in the circulation in extremely low concentrations. Mineralocorticoids are also synthesized in the zona fasciculata DOC is the most potent, but corticosterone and cortisol also have weak mineralo-corticoid activity. All of these steroids are synthesized as products of the glucocorticoid pathway. 

The five major classes of steroid hormones are derived from cholesterol by the pathway illustrated in Figure 34-2. Hydroxylation is important in these conversions. The hydroxylation reactions require NADPH and and are carried out by the cytochrome P450 enzyme system. The enzyme 21-hydroxylase is required for the synthesis of mineralocorticoids and glucocorticoids. 

In the pathway of cortisol synthesis, the 17-hydroxylation of progesterone yields 17-a-hydroxyprogesterone, which, along with progesterone, is transported to the smooth endoplasmic reticulum. There the membrane-bound P450c2i (21-a-hydrox-ylase) enzyme catalyzes the hydroxylation of C21 of 17-a-hydroxyprogesterone to form 11-deoxycortisol (and of progesterone to form deoxycorticosterone [DOC], a precursor of the mineralocorticoid, aldosterone see Fig. 34.23). 

Aldosterone is the primary mineralocorticoid. It retains sodium (and subsequently water) in the blood. It is stimulated in the renin-angiotensin pathway. 

Steroid hormone production occurs on the smooth endoplasmic reticulum and in the mitochondria of the hormone-producing cells. Cholesterol is the precursor of all steroid hormones. The adrenal cortex produces the glucocorticoids, mineralocorticoids, and androgens, whereas the testes synthesize testosterone and the ovaries produce mainly estrogen and progesterone. The relative concentration of the various enzymes determines the final steroid hormone products [4]. Figure 7.4 shows the main pathways for the synthesis of steroid hormones. 

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