The continuing aim of our research program is to define the mechanisms by which the ovarian steroids, especially progesterone, regulate the hypothalamic-pituitary-ovarian axis. This renewal is designed to examine especially the biochemistry and molecular basis of the effects of progesterone and some of its metabolites on pituitary and hypothalamic progesterone-sensitive processes such as gonadotropin and LHRH regulation. Specifically, we hope to elucidate: 1) the characteristics of progestin metabolism in hypothalamic and anterior pituitary tissues and its importance as a regulatory mechanism by examining the nature of the metabolites formed, the properties of the enzymes catalyzing these progestin steroid transformations and the regulation of the metabolism and enzymes, 2) the nature of the sequestered and reacting steroidal compounds; target tissue sites of localization and the mechanisms for sequestering and action at cellular and subcellular levels, 3) the biological relevance of metabolism to progesterone's effects on gonadotropin and LHRH regulation. The information gained is expected to give new insights into the steroidal regulatory mechanisms affecting the hypothalamic-ovarian axis, which might ultimately provide important information on the biomedical aspects of contraception and reveal new avenues for the control of fertility.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Reproductive Biology Study Section (REB)
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University of Wisconsin Madison
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United States
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Karavolas, H J; Hodges, D R (1993) Barbiturates modulate the activity of the pituitary 3 alpha-hydroxysteroid oxidoreductases and inhibit their production of 3 alpha,5 alpha-tetrahydroprogesterone. J Steroid Biochem Mol Biol 45:287-93
Karavolas, H J; Hodges, D R (1993) Changes in pituitary, hypothalamic and brain progestin-metabolizing enzyme activities during lactation. J Steroid Biochem Mol Biol 44:299-303
Hodges, D R; Karavolas, H J (1992) Pituitary progestin-metabolizing enzyme activities in the aged female rat. J Steroid Biochem Mol Biol 41:79-84
Campbell, J S; Karavolas, H J (1990) Purification of the NADPH:5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductase from female rat pituitary cytosol. J Steroid Biochem Mol Biol 37:215-22
Campbell, J S; Karavolas, H J (1990) Characterization of the purified pituitary cytosolic NADPH:5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductase. J Steroid Biochem Mol Biol 37:535-43
Karavolas, H J; Hodges, D R (1990) Neuroendocrine metabolism of progesterone and related progestins. Ciba Found Symp 153:22-44;discussion 44-55
Campbell, J S; Karavolas, H J (1989) The kinetic mechanism of the hypothalamic progesterone 5 alpha-reductase. J Steroid Biochem 32:283-9
Karavolas, H J; Hodges, D; Normand, N et al. (1988) Conversion of 17 alpha-hydroxyprogesterone to 5 alpha, 3 alpha, and 20 alpha-reduced metabolites by female rat anterior pituitary and hypothalamus. Steroids 51:527-41
Bertics, S J; Bertics, P J; Clarke, J L et al. (1987) Distribution and ovarian control of progestin-metabolizing enzymes in various rat hypothalamic regions. J Steroid Biochem 26:321-8
Campbell, J S; Bertics, P J; Karavolas, H J (1986) The kinetic mechanism of the anterior pituitary progesterone 5 alpha-reductase. J Steroid Biochem 24:801-6

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