Development of inhibitor for 20a-hydroxysteroid dehydrogenase

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20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) is an enzyme which catalizes progesterone to a biologically inactive steroid 20alpha-dihydroprogesterone (4-pregnen-20a-ol-3-one : 20alpha-OHP). The activity of this enzyme is found to be distributed in endocrine tissues including the ovary, testis, placenta and adrenal gland. Since progesterone is the precursor of biologically active steroids such as an androgen, estrogen, and corticoid, an increase in this enzyme may alter the regulation of their secretion. 20alpha-HSD is also distributed in a variety of tisuues including T-cells, Macrophage and erthrocytes. Interestingly, enzyme activity is found in spontaneous neoplasms of animals. 20alpha-HSD activity was found in the tissue surrounding the fetus during pregnancy in the rat except for the specific period during which spontaneous fetus loss occurs. Although physiological or pathological role role of 20alpha-HSD has not been determined, it is clear that the enzyme plays a role other than the regulation of steroid secretion and 20alpha-HSD mat be important in may biological process including cytodifferentiation and survival of the cells. To clarify these problems, development of specific inhibitors for 20alpha-HSD has been needed and various steroid derivatives have screened. In the series of the experiment, the derivatives @92STZ-26 is selsected as 20alpha-HSD.This derivative is effective to inhibit purified 20alpha-HSD activity under the invitro condition and in vivo condition.