Paracrine regulation of epithelial progesterone receptor and lactoferrin by progesterone in the mouse uterus.
The objective of this study was to determine whether uterine stromal and/or epithelial progesterone receptor (PR) is required for the antagonism by progesterone (P(4)) of estradiol-17beta (E(2)) action on expression of PR and lactoferrin in uterine epithelium. Uterine tissue recombinants were prepared with epithelium (E) and stroma (S) from wild-type (wt) and PR knockout (PRKO) mice: wt-S+wt-E and PRKO-S+wt-E. P(4) action on epithelial PR expression was studied in wt-S+wt-E and PRKO-S+wt-E tissue recombinants. E(2) down-regulated epithelial PR in both types of tissue recombinants, but P(4) blocked E(2)-induced down-regulation of epithelial PR only in wt-S+wt-E tissue recombinants. Thus, P(4) requires stromal PR to inhibit E(2)-induced down-regulation of epithelial PR. Epithelial PR is not sufficient in itself. The inhibitory effect of P(4) on lactoferrin expression was studied in 4 types of tissue recombinants (wt-S+wt-E, PRKO-S+wt-E, wt-S+PRKO-E, and PRKO-S+PRKO-E). E(2) induced lactoferrin in all 4 types of tissue recombinants. P(4) blocked E(2)-induced lactoferrin expression only in wt-S+wt-E tissue recombinants. In wt-S+PRKO-E tissue recombinants, P(4) inhibited lactoferrin expression only partially. P(4) failed to block E(2)-induced lactoferrin expression in PRKO-S+wt-E and PRKO-S+PRKO-E tissue recombinants. Thus, both epithelial and stromal PR are essential for full P(4) inhibition of E(2)-induced lactoferrin expression.
Kurita
T
T
Department of Anatomy, University of California, San Francisco, California 94143, USA.
Lee
K J
KJ
Cooke
P S
PS
Lydon
J P
JP
Cunha
G R
GR
D000818:Animals; D015152:Blotting, Northern; D015536:Down-Regulation / Q000187:drug effects; D004848:Epithelium / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007781:Lactoferrin / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D010052:Ovariectomy; D019899:Paracrine Communication / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D004965:Estrogen Antagonists; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D011994:Recombinant Proteins; D011374:Progesterone; D004958:Estradiol; D007781:Lactoferrin