Summary. The activity of 20\g=a\-hydroxysteroiddehydrogenase (20\g=a\\x=req-\ HSD) was assayed in the ovaries of rats after accelerated lactation to determine its relationship to the decrease in progesterone secretion that occurs. When rats were subjected to accelerated lactation on Day 9 of pregnancy, activity of the enzyme was only slightly increased by Day 10, but had risen to twice the control level by Day 11, and three times the control level by Day 12. Administration of LH or progesterone pre-vented the increase in enzyme activity. Progesterone concentration had decreased considerably before the time at which any significant increase in 20\g=a\-HSDactivity was detected. These findings are discussed in rela-tion to the role of 20\g=a\-HSDin regulating progesterone levels in the rat.
20alpha-HSD has been initially described as a progesterone metabolizing enzyme of the ovary. On a functional level, ovarian 20alpha-HSD is actively involved in the control of progesterone homeostasis in pregnancy of rats and mice. While 20alpha-HSD expression and activity is downregulated in the corpus luteum of pregnancy, 24 hrs prior to parturition ovarian 20alpha-HSD activity is acutely stimulated. Accordingly, in mice with targeted deletion of the 20alpha-HSD gene, progesterone blood concentration remain high throughout pregnancy which results in a delay of 2–4 days in parturition. Indicating that expression of 20alpha-HSD activity is mandatory for the induction of parturition through reduction of progesterone blood concentration. In mice, 20alpha-HSD is also expressed in the adrenals, kidneys, brain, thymus, T cells and bone marrow. Its induction in hematopoietic cells was used as an assay for the identification of T cell derived factor interleukin-3. In addition, the enzyme reduces and inactivates 17-deoxycorticosterone, the precursor of aldosterone and corticosterone.