Læknablaðið - 15.03.1996, Qupperneq 44

230
LÆKNABLAÐIÐ 1996; 82; 230-1
Nýr doktor í læknisfræði
Þann 2. ágúst 1995 varði Rafn Benediktsson
læknir doktorsritgerð við Háskólann í Edin-
borg. Ritgerðin nefnist The Role of llfi- Hy-
droxysteroid Dehydrogenase in Controlling Foe-
tal Glucocorticoid Exposure. Fer ágrip úr rit-
gerðinni hér á eftir.
Recent epidemiological data have implicat-
ed prenatal events in the development of car-
diovascular disorders. Thus low birth weight
strongly predicts the later occurrence of hyper-
tension, type II diabetes mellitus, syndrome X
and deaths from ischaemic heart disease. The
mechanism linking prenatal events and later
disease is not clear, although maternal maln-
utrition has been advocated. We have ad-
vanced the hypothesis that glucocorticoids
might be important as they retard foetal
growth and programme offspring hypertension
in rats. The foetus has been thought to be
protected from the 2-10 times higher maternal
glucocorticoid levels by the placental enzyme
116- hydroxysteroid dehydrogenase (116-
HSD), which is present in many tissues and in
humans catalyses the conversion of the active
glucocorticoid cortisol to inert cortisone (cort-
icosterone to 11-dehydrocorticosterone in
rats). The precise role of 116-HSD as a barrier
to maternal glucocorticoids during prenatal li-
fe has not been fully characterised. The role of
116-HSD in controlling prenatal glucocorticoid
exposure in humans and animals has thus been
examined. Two isoforms of 116-HSD exist,
type 1, a widespread NADP dependent
reversible enzyme and type 2, a high affinity
NAD dependent dehydrogenase found mainly
in placenta and kidney.
116-HSD was found in abundance in the ov-
ary and placenta. The main site of immun-
ohistochemical staining and expression of
mRNA (116-HSD-l) in the rat ovary was in the
oocyte. 116-HSD was oxidative, inactivating
corticosterone. In both rat placenta in-vitro
(116-HSD-2), and human placenta in-vitro and
ex-vivo (116-HSD-2) the bioactivity was also
predominantly oxidative. The lowest placental
enzyme activity at term (and hence the great-
est foetal glucocorticoid exposure) was found
in the smallest rats with the largest placentas,
i.e. those in human studies who would be
predicted to develop the highest adult blood
pressures (birth weight vs. placental 116- HSD
activity: n = 56; r = 0.46; p < 0.0005).
A method to examine 116-HSD function in
fresh intact human placentas was developed
(ex-vivo dual circuit cotyledon perfusion)
which allows close approximation to the in-
vivo situation. The majority of cortisol, from
low to high nanomolar concentrations, infused
through the maternal circulation was metabol-
ised to inert cortisone by the time it reached
the foetal circulation, although considerable
individual variation was observed. 116-HSD
was the only significant contributor to placent-