The nature of the quantitative relationship
between progesterone secretion and urinary pregnanediol
excretion had been investigated by the
quantitative determination of the metabolite
after continued daily administration of progesterone to normal post-menopausal women, normal
men, hysterectomised-ovariectomised women and
hysterectomised post-menopausal women. These
experiments prove that when the human body is
subjected to the influence of progesterone for
more than a few days, a progressive change in the
relationship of hormone to metabolite occurs so that an increasing proportion of the administered
hormone is recovered from the urine as the
metabolite. This progesterone "priming"
phenomenon has been shown to be attributable to a role of the uterus in the metabolism of
progesterone. Pregnane -3a,20a-diol has been administered to post-menopausal women and the
biochemical mechanism and clinical implications
of these findings have been discussed.(2) The claim by de datteville et al. (1948)
that pre-treatment with a-tocopherol augments the
conversion of administered progesterone to urinary
pregnanediol has been investigated. An identical
experimental procedure has been adopted but normal
human subjects have been studied in place of
patients with carcinoma of the uterus or breast
and the method of Sommerville, Gough and Marrian
(1948) has been used instead of the modified
method of Huber (1947). The results clearly indicate that a-tocopherol does not have the effect
observed by de Watteville et al. when normal
subjects are studied by the former method. Explanations are offered for these contradictory
results.(3) A synthetic orally active progestogen-ethinyltestosterone - has been administered to
normal men and the urine investigated for the
presence of pregnanediol. Significant amounts
of pregnanediol were not recovered from the urine
but large amounts of an unidentified crystalline
precipitate were observed. Excretion of this
substance - which may be metabolite of ethinyltestosterone - as a glucuronide would account for
the results obtained by Allen, Viergiver and
Soule (1944) . The clinical implications of a progestogen which is not metabolised to pregnanediol have been discussed.(4)
The excretion of urinary pregnanediol has
been studied during normal pregnancy and the
results have been compared with those obtained by
less specific methods for the quantitative determination of the steroid. The results emphasise
the necessity to establish values of pregnanediol
excretion in normal pregnancy.(5) It has been shown that the method of
Sommerville, Gough and Marrian (1948) is applicable to the determination of small amounts of
pregnanediol in rabbit urine. The accuracy of
the method when used for this purpose has been
assessed and it is concluded that as little as 0.25 mg. of the steroid can be determined in one half of a twenty -four hour urine specimen.(6) «n analogy has been drawn between the
intermediary metabolisms of progesterone and
cortisone (17-hydroxy-11-dehydrocorticosterone)
and it was anticipated on theoretical grounds that
an abnormality of progesterone metabolism might be
associated with rheumatoid arthritis. Such an
abnormality was demonstrated in a large series of
women and men with rheumatoid
arthritis, and consisted in the conversion of an
abnormally high proportion of administered
progesterone to urinary pregnanediol.The abnormality was not observed in a series
of patients suffering from diseases which
resemble rheumatoid arthritis in one or more of
their clinical features.The belief in the possibility that the pathology of rheumatoid arthritis is associated with
an abnormality of steroid metabolism rather than
with a deficiency of endogenous steroid secretion
was strengthened by the observation that the abnormality is not affected by the administration
of the adrenocorticotrophic hormone of the
anterior pituitary gland.The biochemical mechanism and clinical implications of the abnormality of steroid
metabolism have been considered and the rational
of attempts to modify this abnormality has been
discussed
