Various mutations in the HSD3B2 gene have been shown to be responsible for the varying phenotypic presentations. [6] Missense mutations in the type II gene have been described in nonclassic late-onset 3-beta–hydroxysteroid dehydrogenase deficiency. Various mutations have been described in the type II gene, including T259M and G129R/P222Q mutations in female patients and P222Q in a male patient with salt-wasting. --> 3-beta-hydroxysteroid dehydrogenase (3BHSD) is required for the synthesis of all three groups of adrenal steroids: mineralocorticoids, glucocorticoids, and sex steroids. 3BHSD catalyzes the conversion of pregnenolone to progesterone (mineralocorticoid pathway), 17-alpha-hydroxypregnenolone to 17-alpha-hydroxyprogesterone (glucocorticoid pathway), and dehydroepiandrosterone to androstenedione (sex steroid pathway). Complete absence of this enzyme thus impairs all steroid production. 17OH Preg = 17-alpha-hydroxypregnenolone; DHEA = Dehydroepiandrosterone; 17OH Prog = 17-alpha-hydroxyprogesterone; Andros = Androstenedione; DOC = Deoxycorticosterone; Cmp S = Compound S. Affected 46,XX infants appear normal or may have mild-to-moderate clitoromegaly due to either direct androgen effects of elevated DHEA or peripheral conversion of excess DHEA to testosterone via peripheral type I 3-beta–hydroxysteroid dehydrogenase isoenzyme.
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Several alternative mechanisms for lowering membrane progesterone content late in pregnancy are apparent. Schwarz et al . (1977) found no temporal change in the progesterone synthesizing capacity of the chorion laeve. However, the conversion of pregnenolone to progesterone within the chorion may become inhibited when fetal adrenal DHEAS secretion and cortisol secretion rise late in gestation; simultaneously elevated estrogen synthesis within the membranes from rising amniotic fluid precursors (DHEAS or 16-OH-DHEAS) could have important effects within the membranes or in the adjacent decidua even if placental synthesis is unaltered. FIGURE 4 . Comparison of aromatase activity in human placenta and chorioamnion. Buffer-washed tissue (50 to 100 mg) was suspended in medium containing 1 β - 3 -H-androstenedione and incubated for 18 h. Aromatase activity is expressed as counts per minute of 3 H released per milligram of tissue per hour ( Thompson and Siiteri, 1974a ). Desenhos casinhas.
7, 115–125. doi: 10.1159/000342009. Lin, S. X., Poirier, D., and Adamski, J. (2013). A challenge for medicinal chemistry by the 17beta-hydroxysteroid dehydrogenase superfamily: an integrated biological function and inhibition study. Curr. Top.
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