Effects of a GnRH analogue on human smooth muscle cells cultured from normal myometrial and from uterine leiomyomal tissues.
Leiomyomas are tumours of uterine smooth muscle tissue that are oestrogen and progesterone dependent. When explants of these tumours were grown in culture, the proliferating tissue formed characteristic ball-like aggregates (BLA), rather than the usual hill and valley (HV) pattern of growth of normal myometrial tissue in culture. Immunocytochemical staining with fluorescein isothiocyanate (FITC)-labelled gonadotrophin-releasing hormone (GnRH) revealed that both myometrial and leiomyomal cells have membrane receptors for this hypothalamic releasing hormone. Furthermore, polymerase chain reactions (PCR) with primer sets that were specific for GnRH receptor mRNA, as well as GnRH mRNA, showed that transcripts for both of these nucleic acids are present in myometrial and leiomyomal tissues. The treatment of cultured explants of leiomyomal tissue with a GnRH analogue (buserelin, HOE766) diminished the formation of BLA, but this synthetic hormone had only a moderate effect on the HV topography of normal myometrial tissue. A colorimetric assay indicated that GnRHa inhibited cell proliferation in leiomyomal tissue in a dose-dependent manner. Western blotting, to detect the expression of G1 phase cell cycle-related gene products, showed that cyclin E and p33cdk2 formation in leiomyomas were inhibited by high concentrations of GnRHa. In conclusion, GnRHa might suppress leiomyomal growth by interfering with the expression of cell cycle factors.
Kobayashi
Y
Y
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan.
Zhai
Y L
YL
Iinuma
M
M
Horiuchi
A
A
Nikaido
T
T
Fujii
S
S
D001483:Base Sequence; D002064:Buserelin / Q000494:pharmacology*; D042846:CDC2-CDC28 Kinases; D002455:Cell Division / Q000187:drug effects; D046508:Culture Techniques; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis / Q000235:genetics; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008858:Microscopy, Phase-Contrast; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*
D016213:Cyclins; D017931:DNA Primers; D012333:RNA, Messenger; D011966:Receptors, LHRH; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D002064:Buserelin