Sex steroid receptors in human myometrium and fibroids: changes during the menstrual cycle and gonadotropin-releasing hormone treatment.
The content of estrogen and progesterone receptors (ER, PR) is higher in fibroid tissue than in homologous myometrium, and both receptors seem to be regulated by the levels of circulating sex steroids. Myometrial and fibroid tissues were recovered from women undergoing gynecological operations during different phases of the menstrual cycle and during treatment with an analogue of GnRH (GnRHa). Contents of ER and PR in the tissue cytosol were determined by enzyme immunoassay. The ER levels were significantly higher in fibroid tissue than in homologous myometrium in all the endocrine conditions. During the secretory phase, when luteal progesterone production is prominent, the ER levels in the myometrium and fibroids were lower than during the proliferative phase. During GnRHa treatment, the ER levels in both tissues were similar to those in the proliferative phase but significantly higher than in the secretory phase. The PR levels were also significantly higher in fibroids than in myometrium in all the different endocrine conditions. In both tissues, the PR levels were lower in the secretory phase and during GnRHa treatment, compared with the proliferative phase. Our data suggest that, in these categories of women, both ER and PR are overexpressed in fibroid tissue. Apparently, high progesterone levels down-regulate the ER in both fibroids and myometrium, whereas estrogen mediates the up-regulation of the PR during the proliferative phase. Increased knowledge about the mechanisms by which sex steroids regulate their own receptors in uterine tissues might provide a basis for development of new treatment strategies for women with fibroid disease.
Englund
K
K
Department of Clinical Science, Karolinska Institute, Huddinge University Hospital, Sweden.
Blanck
A
A
Gustavsson
I
I
Lundkvist
U
U
Sjöblom
P
P
Norgren
A
A
Lindblom
B
B
D000328:Adult; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D009215:Myometrium / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone