Topic
Hydroxyprogesterones
About: Hydroxyprogesterones is a research topic. Over the lifetime, 26 publications have been published within this topic receiving 709 citations.
Papers
TL;DR: The metabolism of progesterone by monkey kidney tumor cells transfected with a plasmid vector containing the cDNA encoding the complete amino acid sequence for human cytochrome P450c17 is investigated and it is concluded that progesterone 16 alpha-hydroxylase activity is marked when expressed not only in a heterologous cell expression system but also in human steroidogenic cells.
Abstract: Progesterone and pregnenolone are metabolized to 17 alpha-hydroxysteroids by a cytochrome P450-dependent 17 alpha-hydroxylase (P450c17). The same enzyme can also catalyze the removal of the side-chain of these 17 alpha-hydroxylated steroids to yield androstenedione and dehydroepiandrosterone, respectively. We investigated the metabolism of progesterone by monkey kidney tumor (COS 1) cells transfected with a plasmid vector containing the cDNA encoding the complete amino acid sequence for human cytochrome P450c17. Transfected COS 1 cells converted progesterone to 17 alpha-hydroxyprogesterone as well as 16 alpha-hydroxyprogesterone, but no detectable androstenedione was produced. However, pregnenolone was converted to 17 alpha-hydroxypregnenolone and, ultimately, dehydroepiandrosterone. No 16 alpha-hydroxypregnenolone was produced. The kinetics of progesterone metabolism by the enzyme expressed in COS 1 cells indicated that both 17 alpha- and 16 alpha-hydroxylated products were products were produced from a common active site. Microsomes prepared from fetal adrenal and adult testis converted progesterone to 17 alpha-hydroxyprogesterone as well as 16 alpha-hydroxyprogesterone. No detectable androstenedione was produced by these preparations. Antibodies raised against porcine cytochrome P450c17 inhibited the 17 alpha- and 16 alpha-hydroxylation of progesterone to the same extent when using fetal adrenal microsomes, whereas no inhibition of 21-hydroxylation of progesterone was observed. Similar results were obtained with the imidazole antimycotic agent ketoconazole, which is a preferential cytochrome P450c17 inhibitor. From these results we conclude that human cytochrome P450c17 exhibits marked progesterone 16 alpha-hydroxylase activity in addition to its 17 alpha-hydroxylase function when expressed not only in a heterologous cell expression system but also, importantly, in human steroidogenic cells. Furthermore, the human enzyme has extremely low C-17,20-lyase activity toward progesterone, 17 alpha-hydroxyprogesterone, and 16 alpha-hydroxyprogesterone and fails to convert these to corresponding C19 steroids.
108 citations
TL;DR: Binding to progesterone receptors, glucocorticoid receptors, or expression of progestogen responsive genes is no greater with 17-alpha hydroxyprogesterone caproate than with progester one, suggesting other mechanisms must account for the beneficial effect of 17- alpha hydroxy Progester one caproates on preterm birth rates.
94 citations
TL;DR: The findings indicate that the incubates all contained enzymes involved in the biosynthesis of androgens from progesterone, which was used as substrate for incubated testicular tissue of 1- 10- 13- 17- 20- 30- 40- 60- 90-day-old rats.
Abstract: 7-alpha-3H progesterone was used as substrate for incubated testicular tissue of 1- 10- 13- 17- 20- 30- 40- 60- 90- and 120-day-old rats. Conversion of progesterone to various metabolites was 95% or above in most of the incubates. No age phenomenon was noted. Converstion to testosterone had peaks at both 1 day (44%) and 90 days (47%). The next largest conversion in the 1-day incubate was to androstenedione (5%). This conversion began to reach adult levels (about 10%) after a decline at about 40 days. Conversions to 5-alpha-reduced androgens (androsterone iso-androsterone and 5-alpha-androstanediol) showed biphasic patterns opposite the ones for testosterone and androstenedione. Percent conversions were very low in newborn and adult rats. Regardless of age small amounts of 17-alpha-hydroxyprogesterone and 17-beta-estradiol were found. The findings indicate that the incubates all contained enzymes involved in the biosynthesis of androgens from progesterone.
80 citations
TL;DR: It is postulated that the role of 20α-hydroxysteroid dehydrogenase in regulating androgen formation in the human testis is by competing with steroid 17 α-hydroxylase to utilize pregnenolone and progesterone and by inhibiting steroid 17α-Hydroxylases by its reaction products, 20 α-dihydropregnenol one and 20α,20α-Dihydroprogesterone.
74 citations
TL;DR: The results show that the ovaries of both species produce steroids that are active in the induction of oocyte final maturation and are effective in inducing GVBD in the bioassays.
46 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2007 | 1 |
| 1995 | 1 |
| 1993 | 1 |
| 1988 | 2 |
| 1987 | 1 |
| 1985 | 3 |