The Excretion of Pregnanediol and Adrenocortical Activity

Abstract

A new method of assay was applied to the determination of pregnanediol in urines from patients in whom the presence of a placenta or a corpus luteum could be excluded. The normal variation of pregnanediol content in such urines was examined. It was shown that operative stress or the intravenous administration of corticotrophin caused an increased output of pregnanediol. Quantitatively significant amounts of urinary pregnanediol could not be detected after adrenalectomy nor did adrenalectomized patients respond to corticotrophin by an increased pregnanediol output. It is considered that the adrenal contributes to the pregnanediol found in urine and that the determination of urinary pregnanediol may be of value in the study of adrenal function.Pregnane-3a:20a-diol is a neutral steroid occurring in urine as a conjugate of glucuronic acid. It is a metabolite of progesterone. When progesterone is administered to human subjects, some 10-20% of the hormone can be recovered as urinary preg¬ nanediol. It is generally supposed that the excretion of urinary pregnanediol can be used as a measure of the progesterone produced by the corpus luteum and the placenta. Pregnanediol was first isolated from pregnancy urine by Marrian [1929]. Since then many methods have been proposed for its quantitative deter¬ mination in urine. As these methods have become more reliable, the changes in excretion during the menstrual cycle and pregnancy have been more clearly under¬ stood. It has also become evident that not all the pregnanediol in urine can be accounted for by the activity of either the corpus luteum or the placenta. The work of Engel, Thorn & Lewis [1941] showed that small amounts of authentic 5/?-pregnane3a:20a-diol could be isolated from a large volume of pooled normal male urine. These findings were supported by the work of Heard & Hoffman [1941] and of Westphal [ 1944]. The latter estimated that male urine contained 0-7 mg pregnanediol/1.Although a third source of urinary pregnanediol is now established, its origin has not been conclusively demonstrated. Some of the urinary pregnanediol is thought to originate from the adrenal. Many workers have found an increased pregnanediol output in patients suffering from adrenal disorders.

The Excretion of Pregnanediol During the Normal Menstrual Cycle

“…The methods first evolved for the assay of urinary pregnanediol were lacking in sensitivity. This view is supported by the recent investigations of Klopper, Strong and Cook (1957) who showed that, when ovarian pregnanediol could be excluded, the urinary levels of pregnanediol reflected the activity of the adrenal glands. The original studies showed that pregnanediol was a metabolite of progesterone.…”

The validity and significance of hormone levels in gynaecology

“…There is a characteristic rise in urinary pregnanediol excretion during the ovulatory menstrual cycle, although the extent to which this occurs is rather variable and the difference between levels in the follicular and luteal phase may not be very striking. That this rise is due to extra adrenal precursors was demonstrated by a study after bilateral adrenalectomy (Klopper, Strong and Cook, 1957). If pregnanediol assays are to be used instead of plasma progesterone assays then it is probable that the main field of application is in studying the effect of therapy-notably the induction of ovulation.…”

Heterotransplantation of Rous Sarcoma and Rous Sarcoma Virus to Mammals

“…On th e o th e r h a n d we do n o t know w hy it is n o rm ally p ro d u ced b y th e a d re n a ls in m ales to such an e x te n t th a t th e levels o f " a d re n a l" p reg n an d io l range from 0.38 to 1.42 mg p er 24 hours [44], w hich is alm o st th e sam e level as in p o st m eno p au sal w om en [45] or w hy A CTH p ro duced a four-fold increase in u rin a ry p re g n a n d io l ex cretio n , w hich fell to a v ery low level a fte r b ila te ra l ad re n a le cto in v . T he w eak an d u n c e rta in a c tiv ity o f p ro g esterone on u te rin e can cer [47] seem s to be d u e n o t to its h o rm onal b u t m ore to a c y to s ta tic p ro p e rty [48] as show n by its a c tiv ity on H eL a a n d K B -cells in v itro [49].…”