A New Pathway of Oestriol Biosynthesis in Pregnancy?

Abstract

Incubation of [14C] pregnenolone with sliced adrenal tissue from a newborn anencephalic infant yielded [14C] 16α-hydroxy-dehydroepiandrosterone (16α-OH-D). When [3H]dehydroepiandrosterone (D) was incubated with this tissue, [3H] 16α-OH-D could not be detected. Incubation of [3H] pregnenolone and [14C]D together in equimolar quantities yielded 16α-OH-D containing 3H but not 14C. This evidence suggests that 16α-OH-D can be formed in vitro by the adrenal of the newborn anencephalic infant from a C21 steroid by a pathway which avoids D. 16α-OH-D is an efficient precursor of oestriol in late pregnancy. The pathway demonstrated in vitro could therefore provide another source of oestriol precursor from foetal tissues, similar to that which Kirschner et al. (1966) suggested may operate in maternal tissues.

Corticosteroid Synthesis in Vitro by Adrenal Tissue From Newborn Anencephalic Infants

“…If this is substantiated, it would suggest that the adrenal gland may contribute to the high levels of 16a-hydroxypregnenolone excreted in urine by newborn infants (Shackleton & Mitchell, 1967). Furthermore, 16a-hydroxypregnenolone may be an important intermediate in the synthesis of 16a-hydroxydehydroepiandrosterone by the adrenal of the anencephalic infant (Shahwan et al 1969).…”

“…Photomicrographs of sections of glands used in this study have already been published (Shahwan et at. 1968a(Shahwan et at. , 1969.…”

“…Villee, Loring & Villee (1962) reported briefly that adrenal tissue from an anencephalic infant showed pregnenolone 16a-hydroxylase activity. Shahwan, Oakey & Stitch (1968a, b ;1969) have demonstrated that this tissue contains A5-3/?-hydroxysteroid dehydrogenase-isomerases, steroid 11/?-and 16a-hydroxylases and a C(17)-C(20) desmolase. Cooke (1968) found extensive sulphokinase activity in homogenates of this tissue, fortified with cofactors.…”

Physiology and Genetics of Reproduction

“…Other possibilities have also been suggested (Shahwan et al, 1969;Vokal et al, 1970). However, the quantitative significance of these reactions appears to be limited.…”

Androgen Synthesis in Vitro by Adrenal Tissue From a Newborn Anencephalic Infant

“…The synthesis of one particular C19 steroid, 16a-hydroxydehydroepiandrosterone, from pregnenolone in vitro by adrenal tissue from an anencephalic infant has already been recorded (Shahwan, Oakey & Stitch, 1968a, 1969a and confirmed (Cooke, 1968). We now report the synthesis of other androgens, namely testosterone, androst-4-ene-3,17-dione and ll/?-hydroxyandrost-4-ene-3,l7-dione, in vitro from pregnenolone and progesterone by adrenal tissue obtained from a newborn anencephalic infant.…”