Submitted September 12, 2006
Returned for revision October 4, 2006
Accepted November 9, 2006
Ovary
Low-Density Lipoprotein Receptor-Related 8 (LRP8) Is
Upregulated in Granulosa Cells of Bovine Dominant
Follicle: Molecular Characterization and Spatio-Temporal
Expression Studies
Tania Fayad ,
Réjean Lefebvre ,
Johannes Nimpf ,
David W. Silversides ,
and
Jacques G. Lussier *
* To whom correspondence should be addressed. E-mail: jacques.lussier{at}umontreal.ca.
Abstract
The low-density lipoprotein (LDL) receptor-related protein
8 (LRP8) is a member of the LDL receptor family that acts
in endocytosis and in signal transduction. We cloned the
fulllength bovine LRP8 cDNA in granulosa cells (GC)
of dominant follicle (DF) as well as several LRP8
mRNA splicing variants, including a variant containing a
proline-rich cytoplasmic insert
(A759-K817) involved in intracellular
signaling. Expression of the A759-K817
variant was analyzed in GC of follicles at different
developmental stages: small follicle (SF; 2-4 mm), DF at
day 5 (D5) of the estrous cycle, ovulatory follicles (OF)
24 h after hCG injection, and corpus luteum (CL) at D5.
RT-PCR results show that expression is predominant in GC
of DF compared to other follicles and CL (P < 0.0001)
whereas other related receptors such as LDLR and
VLDLR expression does not differ. Temporal analyses
of follicular walls from OF following hCG treatment reveal
a decrease of LRP8 mRNA expression starting 12 h
post-hCG treatment (P < 0.0001). LRP8 protein is
exclusively localized in GC with highest levels in DF when
compared to SF (P < 0.05). We show that RELN mRNA,
encoding an LRP8 ligand, is highly expressed in theca of
DF when compared to OF (P < 0.004), whereas
MAPK8IP1 mRNA, encoding an LRP8 intracellular
interacting partner is expressed in GC of DF. These
results demonstrate the differential expression of
LRP8, RELN and MAPK8IP1 mRNAs during
final follicular growth and ovulation, and suggest that a
RELN/LRP8/MAPK8IP1 paracrine interaction may regulate
follicular growth.
Key words:
Ovary •
Follicle •
Follicular development •
Granulosa cells •
Ovulation
