Rapid loss of oestrogen and progesterone receptors in human leiomyoma and myometrial explant cultures.
Oestrogen and progesterone are promoters of uterine leiomyoma growth: oestrogen receptors (ER) and progesterone receptors (PR) are over-expressed in these tumours. Paradoxically, there is a heterogeneity in responsiveness of leiomyoma growth to oestrogen and progesterone in culture. In this study, leiomyoma and adjacent myometrium were obtained at hysterectomy. The effect of oestrogen and progesterone on steroid receptor maintenance was examined using minced explants. Quantitative enzyme-linked immunoassay and Northern analysis were performed to assess ER and PR protein and mRNA content respectively. There was an approximately 75% decrease in ER and PR protein content within 8 h of incubation in both leiomyoma and myometrium. The presence or absence of oestrogen and/or progesterone had no effect on receptor protein loss. Northern analysis indicated a parallel loss of ER and PR mRNA transcripts. These findings suggest that the ER and PR expression in leiomyoma may require other extracellular factors. In-vitro studies designed to test the effects of sex steroids and their respective inhibitors on growth and function of leiomyoma and myometrial cells should consider this phenomenon.
Severino
M F
MF
Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland 97201-3098, USA.
Murray
M J
MJ
Brandon
D D
DD
Clinton
G M
GM
Burry
K A
KA
Novy
M J
MJ
D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism*; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol