Molecular and Cellular Endocrinology 182 (2001) 83 – 89
Spatial and topological distribution of progesterone receptor A
and B isoforms during human development
Tsukasa Inoue
a,b,
*, Jun-ichi Akahira
a
, Junji Takeyama
a
, Takashi Suzuki
a
,
Andrew D. Darnel
a
, Chika Kaneko
a
, Yoshimochi Kurokawa
b
, Susumu Satomi
b
,
Hironobu Sasano
a
a
Department of Pathology, Tohoku Uniersity School of Medicine, 2 -1 Seiryo -machi, Aoba -ku, Sendai 980 8575, Japan
b
Second Department of Surgery, Tohoku Uniersity School of Medicine, Sendai, Japan
Received 12 November 2000; accepted 14 May 2001
Abstract
Progesterone receptor (PR) is a member of the nuclear receptor superfamily. To date, two isoforms of PR have been identified,
PR-A and PR-B. In progesterone responsive tissues, the relative ratio of PR-A and PR-B is considered to contribute to the
tissue-specific actions of progesterone. In this study, we examined the distribution of PR-A and PR-B in human fetal tissues
ranging from 11 to 40 gestational weeks using immunohistochemistry and RT-PCR analysis. PR immunoreactivity was detected
in a wide range of fetal tissues until 20 weeks of gestation, but gradually decreased towards the late gestational period. However,
PR continued to remain positive throughout the gestational period in the interstitial cells of Cajal and endocrine tissues. PR-B was
demonstrated as the predominant isoform in comparison to PR-A in all fetal tissues examined. These findings suggest that
progesterone may be involved in the development of fetal organs throughout the gestational period. © 2001 Elsevier Science
Ireland Ltd. All rights reserved.
Keywords: Progesterone receptor; Human fetal tissue; Immunohistochemistry; Reverse transcriptase-polymerase chain reaction
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1. Introduction
Progesterone is synthesized in syncytiotrophoblasts
of the human placenta, continuously increasing in pro-
duction during pregnancy. This sex steroid plays essen-
tial roles throughout the course of pregnancy, including
the maintenance of pregnancy, the onset of labor, inhi-
bition of uterine contractions, development of the
mammary glands, regulation of placental functions and
other (Shanker and Rao, 1999). These relatively diverse
effects of progesterone are all mediated through its
binding to a specific intranuclear receptor, the proges-
terone receptor (PR) (Tsai and O’Malley, 1994).
PR belongs to the nuclear receptor superfamily and,
to date, two isoforms of this receptor have been iden-
tified, PR-A and PR-B, 94 and 114 kDa in size, respec-
tively, as with other members of this family (Horwitz
and Alexander, 1983). The PR-B isoform is a full-
length receptor, whereas the PR-A isoform lacks 164
amino acids in the N-terminus of the PR-B isoform.
Both PR-A and PR-B are derived from transcripts
initiated from two distinct estrogen-inducible promoters
within a single-copy of the PR gene (Kastner et al.,
1990). Both isoforms have been demonstrated to func-
tion as ligand-activated transcription factors, but they
are not always equal in their functional properties and
progesterone actions (Vegeto et al., 1993). PR-B is
transcriptionally more active than PR-A, but when
compared with PR-A, PR-B activity is cell-specific (Sar-
torius et al., 1994). In addition, the PR-A isoform has
been demonstrated to repress the transcriptional activi-
ties of other steroid hormone receptors including the
estrogen receptor and PR-B (Vegeto et al., 1993; Mc-
Donnell and Goldman, 1994; McDonnell et al., 1994;
Kraus et al., 1995). Therefore, the relative levels of
PR-A and PR-B within target cells may contribute to
* Corresponding author. Tel.: +81-22-717-7440; fax: +81-22-717-
7449.
E-mail address: tsukasai@gonryo.med.tohoku.ac.jp (T. Inoue).
0303-7207/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved.
PII:S0303-7207(01)00549-4