The Metabolism of Progesterone and Its Related Compounds in Human Pregnancy

Davis, M. Edward; Plotz, E. J.; Lupu, Charles I.; Ejarque, Peter M.

doi:10.1016/s0015-0282(16)33662-7

Cited by 31 publications

(8 citation statements)

References 17 publications

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“…In this respect the retro-steroids apparently distinquish themselves from progesterone, whose 4-ene-3-one configuration was shown to be the primary site of metabolic attack (Davis & Plotz, (5). Probably the difference in metabolic pattern between normal and retrosteroids is associated with the fact that the latter are orally effective whereas progesterone is not.…”

Section: Discussionmentioning

confidence: 99%

Dydrogesterone: Metabolism in man

Amsterdam

Overmars

et al. 1980

European Journal of Drug Metabolism and Pharmacokinetics

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An investigation of the urinary metabolites of the oral progestational agent dydrogesterone in healthy women of childbearing age is reported. The drug was administered in 3H-labelled form and the urine of the first 8 h, containing on average 38% of the radioactivity administered, was used as the source of the metabolites. It was fortified with urine collected during the first 8 h of a similar study with nonlabelled dydrogesterone. After enzymatic hydrolysis of conjugated metabolites, 43 different chemical species were isolated by means of extraction, followed by column and thin layer chromatography. Three of these metabolites, constituting about 70% of the urinary radioactivity, were positively identified as 20 alpha-hydroxy-9 beta, 10 alpha-pregna-4, 6-diene-3-one (52%), 21-hydroxy-9 beta, 10 alpha-pregna-4, 6-diene-3, 20-dione (18%) and 16 alpha-hydroxy-9 beta, 10 alpha-4, 6-diene-3, 20-dione (1%). Of the remainder, 20 (13%) were tentatively characterized as various products of oxidative attack, all probably having the 4, 6-diene-3-one configuration intact. It is concluded that the 4, 6-diene-3-one configuration is metabolically stable in combination with the 9 beta, 10 alpha configuration. This finding may explain why dydrogesterone, in contrast no progesterone, is orally effective, and lacks estrogenic properties.

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Section: Discussionmentioning

confidence: 99%

Dydrogesterone: Metabolism in man

Amsterdam

Overmars

et al. 1980

European Journal of Drug Metabolism and Pharmacokinetics

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“…These levels (20-60 ng/ml) could be interpreted as the result of a high production of DHP either directly from the placenta or corpus Iuteum or, more likely, by a high peripheral con¬ version from progesterone as has been shown to occur in the brain of the monkey and rabbit . The latter interpretation is in conflict with the established predominance of the 5ß-pathway in progesterone metabolism in vivo (Chang et al 1960;Davis et al 1960). However, the impor¬ tance of this pathway was based on identification of less than 30% of labelled metabolites recovered in urine and bile after iv injection of [14C]progesterone (Chang et al 1960).…”

Section: Discussionmentioning

confidence: 96%

“…It seems unlikely that these levels should be the result of a high peri¬ pheral 5a-reduction of progesterone since, in the human, progesterone metabolism has been shown to proceed mainly through the formation of 5ß-reduced steroids (Chang et al 1960;Davis et al 1960). High levels of DHP could also be explained by a low clearance rate caused by binding to high affinity binding proteins as has been shown to occur in the pregnant guinea pig (Illingworth et al 1970;Lea 1973b;Lea et al 1976).…”

mentioning

confidence: 99%

Binding of 5α-dihydroprogesterone to proteins in human pregnancy serum

Lea

1982

Acta Endocrinologica

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The binding of 5\g=a\-dihydroprogesterone (DHP)1 to proteins in pregnancy serum has been investigated and compared with the binding of progesterone. Characteristic properties of the DHP-serum protein interaction were unsaturability, low affinity and poor complex stability. Fractionation of serum using a variety of protein separation techniques, revealed that DHP interacts with several proteins. At low temperature (0\ p=n-\ 4\ s=deg\ C) albumin appeared to be the principal binding component whereas higher temperatures seemed to favour binding to \g=b\-lipoproteins and \g=a\2-macroglobulin. Binding to specific binding proteins such as the corticosteroid binding globulin (CBG) and the sex hormone-binding globulin, (SHBG) were detectable but appeared to be quantitatively unimportant. Progesterone showed a similar multicomponent interaction but differed from DHP in the extent of binding to CBG. Binding of either hormone to the \g=a\1-acid-glycoprotein was negligible. The present study shows that the high endogenous DHP levels present in pregnancy sera are caused by factors other than high affinity protein binding. 5a-Dihydroprogesterone (DHP) is structurally very similar to progesterone and yet very little is known about its biological function and activity. The ana¬ logous relationship between 5a-dihydrotestosterone and testosterone has been the subject of extensive investigation and evidence has accumulated to suggest that 5rx-dihydrotestosterone is the actual intracellular androgen (Mainwaring 1977).

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“…Berliner & Wiest, 1956), and it seems likely that this organ plays a most important role in the removal of these large amounts of progesterone from the blood. Another significant factor is the uptake of progesterone by various body tissues, in particular fatty tissue (Zander, 1959;Davis et al 1960). Considerable variation between individual animals was noted.…”

Section: Metabolism Of Injected Progesteronementioning

confidence: 99%

“…In man, the cow and the rabbit, the only species so far fully investigated, injected progesterone is removed from the blood at a very rapid rate (Raeside & Turner, 1955;Rappoport, Goldstein & Haskins, 1957;Soiva, Haskins & McCafferty, 1959;Zander, 1959; Davis, Plotz, Lupu & Ejarque, 1960;cf. also Short, 1961).…”

Section: Introductionmentioning

confidence: 99%

The Metabolism of Injected Progesterone in the Ewe

Brush¹

1963

Journal of Endocrinology

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Plasma levels of progesterone and 20 \g=a\-hydroxypregn-4-en-3-one have been studied after intravenous (i.v.) and intramuscular (i.m.) injections of progesterone in sheep. I.v. injected progesterone was removed from the bloodstream very rapidly and it was necessary to give 50 mg. before it was possible to detect progesterone at times up to 10 min. after the injection. With 100 mg. amounts of progesterone injected i.v. the mean concentration in samples taken up to 10 min. after the injection was 34\m=.\7 \g=m\g./100 ml. plasma (range 4-110 \g=m\g./100 ml. in 9 samples), but after 1 hr. the mean level was 2\m=.\2 \g=m\g./100 ml. plasma (range 0-10 \g=m\g./100 ml. in 10 samples).The concentrations of 20 \g=a\-hydroxypregn-4-en-3-one were usually, but not always, less than those of progesterone. When progesterone was given by i.m. injection it was not possible to establish detectable blood levels. The effect of the injection vehicle was also studied for each injection route.

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The Metabolism of Progesterone and Its Related Compounds in Human Pregnancy

Cited by 31 publications

References 17 publications

Dydrogesterone: Metabolism in man

Dydrogesterone: Metabolism in man

Binding of 5α-dihydroprogesterone to proteins in human pregnancy serum

The Metabolism of Injected Progesterone in the Ewe

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