Neuroendocrine Metabolism of Progesterone and Related Progestins

  1. Derek Chadwick Organizer and
  2. Kate Widdows
  1. Harry J. Karavolas and
  2. Donald R. Hodges

Published Online: 28 SEP 2007

DOI: 10.1002/9780470513989.ch3

Ciba Foundation Symposium 153 - Steroids and Neuronal Activity

Ciba Foundation Symposium 153 - Steroids and Neuronal Activity

How to Cite

Karavolas, H. J. and Hodges, D. R. (2007) Neuroendocrine Metabolism of Progesterone and Related Progestins, in Ciba Foundation Symposium 153 - Steroids and Neuronal Activity (eds D. Chadwick and K. Widdows), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470513989.ch3

Author Information

  1. Department of Physiological Chemistry, University of Wisconsin, 587 Medical Sciences Building, 1300 University Avenue, Madison, WI 53706, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471926894

Online ISBN: 9780470513989



  • neuroendocrine metabolism;
  • progesterone;
  • progestins;
  • metabolic processing;
  • metabolites


In mammalian neuroendocrine structures the metabolic processing of progesterone and related natural progestins is primarily a reductive process involving the C-4,5 double bond and the C-3 and C-20 ketones. The principal products of the neuroendocrine metabolism of progesterone in female rats are the two 5α- and 3α-reduced metabolites, 5α-dihydroprogesterone and 3α,5α-tetra-hydroprogesterone, with lesser amounts of the corresponding 20α-reduced products. Certain of these metabolites produce some, but not all, of progesterone's biological effects. 5α-Dihydroprogesterone and 3α,5α-tetrahydroprogesterone, in particular, have potent progesterone-like effects on neuroendocrine functions, such as gonadotropin regulation. The two other principal ovarian progestins, 20α-dihydroprogesterone and 17α-hydroxyprogesterone, are metabolized in an analogous manner. The major neuroendocrine progestin conversions therefore appear to be 5α-reduction and 3α-hydroxysteroid oxidoreduction. In the hypothalamus and anterior pituitary, the enzymic activities that catalyse these conversions appear to be under ovarian control and appear to vary with changing reproductive states. These quantitative changes in processing, together with the potent progesterone-like effects of certain metabolites, suggest that these neuroendocrine conversions may provide an important mechanism for mediating some of the effects of progesterone. Alternatively, some metabolites, by duplicating selected effects of progesterone, may provide a means of prolonging certain of its effects while others are terminated.