RU486 suppresses prolactin production in explant cultures of leiomyoma and myometrium

Fertil Steril. 1996 Jun;65(6):1119-24.

Abstract

Objective: To assess the action of RU486 (mifepristone), in the presence and absence of P, on PRL production by explant cultures of leiomyoma and myometrium.

Design: Explant cultures using tissue from nine premenopausal women undergoing hysterectomy in the proliferative phase of the menstrual cycle; immunohistochemical staining of tissue sections from five patients for P receptor (PR) subtype.

Main outcome measures: Prolactin secretion (measured by RIA), lactate dehydrogenase secretion (measured by quantitative colorimetric assay), and immunohistochemistry for PR subtype.

Results: Prolactin secretion was decreased in leiomyomas by RU486 at concentrations of 10(-7) M and 10(-5)M when normal serum-containing medium was used. In experiments with all detectable P removed from serum, PRL secretion was suppressed in both leiomyomas and myometrium at an RU486 concentration of 10(-7)M. Immunohistochemistry results suggest that the A form of the PR is the dominant form in both leiomyomas and myometrium.

Conclusions: Prolactin production is suppressed in both leiomyomas and myometrium after treatment with RU486 in vitro, and this suppression may serve as a marker for the clinical effectiveness of agents used in the treatment of leiomyomas.

PIP: Uterine leiomyomas are the most common benign neoplasms of the uterus. They appear to be estrogen dependent. The role of progestins in regulating leiomyoma growth is, however, less clear. Studies have suggested that RU486 may provide long-term medical treatment for women with leiomyomas. The authors investigated the mechanism of action of RU486 on uterine leiomyomas and myometrium, using prolactin production as a marker. Explant cultures using tissue from nine premenopausal women undergoing hysterectomy in the proliferative phase of the menstrual cycle were used, along with the immunohistochemical staining of tissue sections from five patients for P receptor (PR) subtype. Prolactin production was suppressed in both leiomyomas and myometrium after treatment with RU486 in vitro. This suppression may be a marker for the clinical effectiveness of agents used to treat leiomyomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Culture Media
  • Estradiol / pharmacology
  • Female
  • Humans
  • Hysterectomy
  • Immunohistochemistry
  • L-Lactate Dehydrogenase / metabolism
  • Leiomyoma / metabolism*
  • Menstrual Cycle
  • Mifepristone / pharmacology*
  • Myometrium / drug effects
  • Myometrium / metabolism*
  • Progesterone / pharmacology
  • Prolactin / biosynthesis*
  • Tumor Cells, Cultured

Substances

  • Culture Media
  • Mifepristone
  • Progesterone
  • Estradiol
  • Prolactin
  • L-Lactate Dehydrogenase