In pregnant rock hyraxes isolated leucocytes metabolise both [H-3]pregnenol
one and [H-3]progesterone while whole blood, erythrocytes and an erythrocyt
e/leucocyte mixture only metabolised [H-3]progesterone. Plasma displayed no
tendency to metabolically convert any one of these two steroids. In whole
blood [H-3]progesterone appears to be converted to 5 alpha -pregnane-3,20-d
ione and a compound with chromatographic properties similar to that of 5 al
pha -pregnan-3 alpha -ol-20-one. 5 alpha -Pregnane-3,20-dione exhibited a h
igh relative binding affinity for the uterine progesterone receptor (94%),
but 5 alpha -pregnan-3 alpha -ol-20-one displayed very little affinity for
the same receptor (0.4%). 5 alpha -Pregnane-3,20-dione may therefore aid in
the maintenance of pregnancy. Corpora lutea metabolised progesterone to 17
alpha -hydroxyprogesterone, a compound exhibiting no progestational functi
on because of its low relative binding affinity for the uterine progesteron
e receptor (2%). Progesterone appears to be the main product of the corpus
luteum. However, 5 alpha -pregnane-3,20-dione circulated at concentrations
approximately 8.5 times higher than progesterone, probably due to the metab
olic conversion of progesterone to 5 alpha -pregnane-3,20-dione by the bloo
d. We conclude that in the hyrax progesterone, produced by the corpora lute
a, enters the circulation, where it is reduced to 5 alpha -pregnanes. 5 alp
ha -Pregane-3,20-dione may then be transported to the uterus where it binds
to the progesterone receptor to assist in the maintenance of pregnancy. Th
is mechanism appears to be analogous to that of the African elephant which
is phylogenetically related to the hyrax, except that in the elephant the S
et-reduced metabolites are produced by luteal tissue and not the blood. (C)
2001 Elsevier Science Inc. All rights reserved.