Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Additional information

In humans, progesterone is converted by reduction, hydroxylation, side-chain cleavage and conjugation. Qualitative (Aufrère & Benson, 1976) and quantitative (Little et al, 1975) species differences have been observed. In humans, most progesterone is metabolized by reductases, the main product being pregnanediol (5b-pregnane-3a,20a-diol), excreted as the glucuronide. In chimpanzees, progesterone is metabolized similarily, and pregnanediol is the major excretion product (YoungLai et al., 1975); some human primates, such as baboons and rhesus monkeys, excrete androsterone as the major urinary product, implying that in these species side-chain cleavage predominates (Aufrère & Benson, 1976; Isihara et al, 1975). Some species excrete acidic progesterone metabolites, i.e. metabolites that arise from hydroxylation at C-21 and further oxidation to the C-21 -carboxyl derivative in the urine (Senciall & Dey, 1976). Rabbits excrete the largest amounts of this type of metabolite, followed by guinea-pigs, pigs and rats. Only negligable amounts are found in human urine (Senciall et al, 1976). Extrahepatic metabolism of progesterone also occurs to an appreciable extent. In rats, for instance, submaxillary gland tissue has been shown to contain 5a-reductase, 20a-reductase and 17a-hydroxylase (Coffey, 1973). Circulating progesterone can be utilized by the adrenals for the production of corticosteroids like aldosterone and corticosterone, as demonstrated by Vecsei & Kessler (1971) in rats.

References

Aufrère, M.B. & Benson, H. (1976) Progesterone: an overview and recent advances. J. pharm. Sci. 65, 783-800.

 Coffey, J.C. (1973) In vitro progesterone metabolism in rat submaxillary gland: the formation of 20a-hydoxy-4-pregnen-3-one and other substances. Steroids 22, 561-566.

 Ishihara, M., Osawa, Y., Kirdani, R.Y. & Sandberg, A.A. (1975) Progesterone metabolism in the baboon. J. Steroid Biochem. 6, 1213-1218.

 Little, B., Billiar, R.B., Rahman, S.S., Johnson, W.A., Takaoka, Y. & White, R.J. (1975) IN vivo aspects of progesterone distribution and metabolism. Am. J. Obstet. Gynecol. 123, 527-534.

 Senciall, I.R. & Dey, A.C. (1976) Acidic steroid metabolits: evidence for the excretion of C-21-carboxylic acid metabolites of progesterone in rabbit urine. J. Steroid Biochem. 7, 125-129.

 Senciall, I.R., Harding, C.A. &Dey, A.C. (1976) Acidic steroid metabolites: species differences in the urinary excretion of acidic metabolites of progesterone. J. Endocrinol. 68, 169-170.

 Vecsei, P & Kessler, H. (1971) In vivo conversion of radioactive progesterone and corticosterone to adrenal cortical hormones in normal and ACTH-treated rats. Acta endocrinol.68, 759-770.

 YoungLai, E.V., Graham, C.E. & Collins, D.C. (1975) Metabolism of 4-14C-progesterone in the adult female chimpanzee. Steroids, 25, 465-476.