Cycle-dependent endometrial expression and hormonal regulation of the fibulin-1 gene.
Fibulin-1 is a secreted protein associated with elastic matrix fibres and basement membranes. It plays a role in stabilizing blood vessels and can also regulate cell motility and invasiveness. We studied the regulation of the fibulin-1 gene in the rat and human endometrium, an organ where cyclic tissue remodeling and angiogenesis take place. The rat fibulin-1C and -1D-specific DNA sequences were first identified and a comparison of the deduced amino acid sequence with the mouse and human counterparts showed a very strong conservation. The exon-intron structure was also maintained. Primers were derived for RT-PCR analysis of fibulin-1 expression in rat endometrium. The highest levels of fibulin-1C and -1D transcripts were measured at metestrous and diestrous, and in early pregnancy at day 3 post-coitum. In vivo studies showed stimulation of endometrial fibulin-1D expression after estrogen application, an effect prevented by parallel treatment with progesterone. Analysis of human endometrial tissues indicated that the fibulin-1D transcript levels were higher during the mid-secretory phase than during the proliferative and early secretory phases. Cultured human endometrial stromal cells treated with progesterone responded with a dramatic increase of fibulin-1 protein expression. This was enhanced by parallel treatment with epidermal growth factor and prevented by application of the antiprogestin RU486. Altogether the results show a cycle-dependent regulation of endometrial fibulin-1 expression controlled by both progesterone and estrogen. Based on its implication in tissue remodeling and angiogenesis, fibulin-1 may play an important role in endometrial receptivity for embryo implantation.
Haendler
Bernard
B
Research Laboratories of Schering AG, Berlin, Germany. bernard.haendler@schering.de
Yamanouchi
Hiroshi
H
Lessey
Bruce A
BA
Chwalisz
Kristof
K
Hess-Stumpp
Holger
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D004717:Endometrium / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D030762:Estrous Cycle / Q000235:genetics / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008597:Menstrual Cycle / Q000235:genetics / Q000502:physiology*; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D008969:Molecular Sequence Data; D011247:Pregnancy; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017154:Stromal Cells / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D004967:Estrogens; D016326:Extracellular Matrix Proteins; C060820:fibulin; D015735:Mifepristone; D011374:Progesterone; D004815:Epidermal Growth Factor