Molecular Human Reproduction, Vol 4, 1110-1115, Copyright © 1998 by Oxford University Press
A Salmi, P Pakarinen, AM Peltola and EM Rutanen
The major regulators of endometrial function are oestrogen and
progesterone, which act through binding their nuclear receptors and by
activating transcription of their target genes. Interactions between
steroid receptors and transcription proteins, e.g. c-JUN/AP-1, can modulate
steroid action at the transcriptional level. The 19-
nortestosterone-derived progestin, levonorgestrel, is used for
contraception, treatment of menorrhagia and for endometrial protection
during hormone replacement therapy, but the signalling pathways of its
action are totally undefined. We examined the effect of an intrauterine
system, releasing 20 microg of levonorgestrel per 24 h (LNG-IUS), on
immunoreactive oestrogen receptor, progesterone receptor, c-JUN and Ki- 67
expression in 29 endometrial specimens, obtained from fertile women using
the LNG-IUS for contraception. Moderate to strong immunostaining for
oestrogen receptors was observed in the stromal cells in all specimens, in
glandular epithelial cells in 26 cases and in flattened luminal epithelial
cells in 17 specimens. Decidualized stromal cells showed no progesterone
receptor immunoreactivity in 19 of the 29 specimens, and weak to moderate
immunostaining in 10 cases. Luminal epithelial cells were negative for
progesterone receptor in all samples. Intense nuclear staining for C-JUN
was observed in epithelial cells in 26 and in decidualized stromal cells in
all 29 of the samples. In 16 samples, Ki-67 immunoreactivity was evaluated
as weak to moderate in decidualized stroma, and in 13 samples absent. Our
data demonstrate that intrauterine release of LNG maintains constant
expression of C-JUN and exerts progestational effects in the endometrium in
the absence of progesterone receptors. In contrast, LNG-IUS inhibits
several cellular responses to oestrogen despite the presence of endogenous
oestrogen and oestrogen receptors. These data suggest that the
progestational effects induced by progesterone and levonorgestrel are
mediated through different signalling pathways.
JOURNAL ARTICLE
The effect of intrauterine levonorgestrel use on the expression of c- JUN, oestrogen receptors, progesterone receptors and Ki-67 in human endometrium
Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Finland.
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