Læknablaðið - 15.03.1996, Blaðsíða 45

LÆKNABLAÐIÐ 1996; 82
231
al cortisol metabolism at physiological matern-
al concentrations and inhibition of 1113- HSD
with either the liquorice constituent glycyrr-
hetinic acid or its hemi-succinate, carbenoxo-
lone, resulted in abolition of the glucocorticoid
barrier, allowing maternally administered
cortisol to pass unmetabolised through the
placenta. In a prospective study, on 16 normal
primiparous women whose placentas were stu-
died with this technique, a positive and signif-
icant correlation was found between the ef-
fectiveness of 116-HSD and offspring birth
weight (r = 0.67; p < 0.005).
The relationship between placental 116-
HSD effectiveness in-vivo and term cord blood
osteocalcin (a sensitive marker of glucocort-
icoid exposure) was prospectively examined in
19 women. Cord blood levels of the bone
specific protein osteocalcin were determined
with radioimmunoassay. The lowest cord
blood osteocalcin levels were found in the
foetuses whose placental 116-HSD barrier
function was poorest (r = 0.58; p < 0.02), (and
had presumably had the greatest glucocort-
icoid exposure), suggesting that term cord
blood osteocalcin levels might be a useful
predictor of hypertension, ischaemic heart dis-
ease and possibly metabolic bone disease.
The findings presented in this thesis repres-
ent direct evidence that 116-HSD is the barrier
to maternal glucocorticoids, its effectiveness
correlating with foetal growth in rats (in-vitro),
in humans (ex-vivo), and in-vivo with human
cord blood osteocalcin levels (osteocalcin may
be a marker of glucocorticoid exposure). In
the light of studies on pregnant rats in which
administration of exogenous glucocorticoids
or 116-HSD inhibitors reduces birth weight and
programmes hypertension in the offspring, it is
reasonable to propose that increased foetal
glucocorticoid exposure consequent upon att-
enuated placental 116-HSD function may play
a role in intrauterine programming of later
hypertension.