Abstract
17β-Hydroxysteroid dehydrogenases (17HSDs)/17-ketosteroid
reductases (17KSRs) modulate the biological activity of certain
estrogens and androgens by catalyzing dehydrogenase and reductase reactions
between 17β-hydroxy and 17-ketosteroids.
In the present study, cDNAs encoding mouse and rat 17HSD/KSR1
were cloned in order to study the role of rodent type 1 enzyme in
ovarian estradiol (E2) biosynthesis and its
enzymatic characteristics. Both rat and mouse 17HSD/KSR1
were expressed in granulosa cells of developing follicles, where
diethylstilbestrol and follicle-stimulating hormone stimulated follicular
maturation and up-regulated the expression of 17HSD/KSR1,
whereas human chorionic gonadotropin caused luteinization of follicles
and down-regulation of the enzyme. In line with this, the rodent
type 1 enzymes are not expressed in the corpus luteum (CL). Mouse
17HSD/KSR1 showed substrate specificity different from
that of the human counterpart. The mouse type 1 enzyme catalyzed
the reaction from androstenedione to testosterone at least as efficiently
as estrone (E1) to E2,
while human 17HSD/KSR1 clearly preferred the E1 to
E2 reaction.
A mouse mammary epithelial cell line was found to possess
strong estrogenic 17KSR activity. A novel type of 17HSD/KSR
responsible for this activity was expression-cloned on the basis
of its ability to convert E1 to E2 and
it was chronologically named 17HSD/KSR7. Interestingly,
it showed 89 % identity with a rat protein called prolactin
receptor-associated protein (PRAP), which is expressed in the CL.
Enzymatic characterization showed that both mouse 17HSD/KSR7
and PRAP efficiently catalyzed the reaction from E1 to
E2. The mouse type 7 enzyme was most abundantly expressed
in the ovary and placenta. Similar primary structure, enzymatic
characteristics, and tissue distribution of mouse 17HSD/KSR7
and PRAP suggest that PRAP is rat 17HSD/KSR7.
Further studies showed that in rat ovaries 17HSD/KSR7
is primarily expressed in the middle and second half of pregnancy,
in parallel with E2 secretion from the CL.
Using in situ hybridization, cell-specific expression of 17HSD/KSR7
was studied in the mouse ovary, uterus and placenta. In the mouse
ovary, the enzyme was expressed exclusively in the CL. In the uterus
on day 5 post coitum (p.c.), the type 7 enzyme was expressed in
the decidua, mostly in the inner zone of antimesometrial decidua.
Between day 8 and 9 p.c. the enzyme was abundant in decidua capsularis
of the developing placenta, after which expression moved to the
basal zone. On days 12 and 14 p.c., mouse type 7 enzyme was abundantly
expressed in the spongiotrophoblasts, where expression decreased
towards parturition. Altogether, rodent 17HSD/KSR7 is a
new 17HSD/KSR which is involved in the biosynthesis of
E2 in the ovaries. In addition, E2 produced
locally in the decidua and placenta by the type 7 enzyme may have
a role in decidualization and/or implantation and placentation.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-5751-0 |
| Date | 22 August 2000 |
| Creators | Nokelainen, P. (Pasi) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 2000 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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