Where does each deficiency occur?

 

A deficiency in P450scc, for example results in an inability to synthesize progestin's, glucocorticoids, mineralocorticoids, androgens and estrogens. A deficiency of 3 beta HSD prevents the synthesis of both mineralocorticoid and glucocorticoid in the adrenal cortex. It also prevents synthesis of androstenedione, testosterone, estrone and estradiol in the ovaries and testes.

However the adrenals and gonads do make elevated amounts of the weak androgen DHEA due to ACTH stimulation of the adrenals and LH stimulation of the gonads. A deficiency in P450c 17, on the other hand, results in elevated progesterone due to an inability to synthesize cortisol which interrupts the negative feedback of cortisol on the hypothalamus which responds in turn by producing increased corticotropin-releasing hormone or CRH which stimulates the pituitary to produce increased ACTH, which in turn stimulates hyperplasia known as congenital adrenal hyperplasia and over stimulation of the adrenal cortex by ACTH.

There is not an increase in adrenal androgen production in P450c 17 deficiency because the androgens cannot be synthesized. A deficiency of 17 beta HSD would prevent the synthesis of the most active androgen, testosterone, and the most active estrogen, estradiol. However, the weak androgen androstenedione and the weak estrogen estrone would be synthesised so the effects on androgen and estrogen target tissues would not be as severe as in P450c 17 deficiency.

A deficiency in P450c 21 the most common steroidogenic deficiency prevents the synthesis of glucocorticoid and mineralocorticoid as a result the lack of cortisol negative feedback results in over stimulation of the adrenal cortex by ACTH with excess synthesis of progestins and androgens in the zona fasciculata and zona reticularis and excess synthesis of progestins in the zona glamurosa.

A deficiency of P450 aromatase would prevent the synthesis of estrogens, since estrogens are synthesised denovo in the gonads and by peripheral conversion of androgens. The effects of P450 aromatase deficiency on estrogen target tissues would be severe. A deficiency of P450 algo, the iso form of 11 hydroxylase in the zona glomarulosa, would result in a deficiency of aldosterone.

However over stimulation of the zona glomarulosa by androtension 2, would stimulate DOC synthesis, so that the consequences for water and electrolyte balance would be modest. A deficiency of 5 alpha-reductase would prevent the development of dihydrotestosterone dependent tissues, high levels of testosterone which binds to the same receptors as DHT can partially overcome the effects of 5 alpha-reductase deficiency.

A deficiency in P450c 11 which would occur only in the zona fasiculata and the zona reticularis of the adrenal cortex would result in a deficiency of cortisol. The interruption of cortisol negative feedback would result in overstimulation of the adrenal cortex by ACTH which would result in excess production of progestins, androgens and the mineralocorticoid DOC.