Evidence for a Müllerian-inhibiting substance autocrine/paracrine system in adult human endometrium.
OBJECTIVE
To determine if adult human endometrium possesses an intact müllerian-inhibiting substance (MIS) signal transduction system and, if so, whether MIS can modulate endometrial cell viability.


METHODS
Adult human endometrial tissue was subjected to reverse transcription polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. In addition, cultured human endometrial stromal cells were treated with recombinant MIS or transiently transfected with MIS and/or MIS type II receptor (MISRII) expression plasmids to assess for effects upon endometrial cell viability and apoptosis. The MIS in conditioned media was quantified by specific ELISA.


METHODS
Academically affiliated medical center.


METHODS
Reproductive-age women undergoing routine infertility evaluation.


METHODS
Endometrial sampling.


METHODS
Assessment of MIS gene transcription and protein translation in human endometrial tissue in vivo and in vitro.


RESULTS
1) The RT-PCR revealed that adult human endometrium expresses the genes for MIS, MISRII, ALK3, and Smads 1 and 9. 2) Immunohistochemistry reveals that MIS and MISRII protein are expressed in human endometrium. 3) Immunocytochemistry of cultured human endometrial cells reveals that MIS and MISRII protein are primarily restricted to mitosing cells. 4) ELISA reveals that MIS is secreted by human endometrial cells in vitro and that this process is increased by sex steroids. 5) Increasing local MIS concentration in cultured human endometrial stromal cells either by exogenous administration or transient transfection significantly decreases cell viability and increases apoptosis.


CONCLUSIONS
Adult human endometrium possesses a functional MIS signal transduction system which negatively regulates cellular viability.
Wang
Jeff
J
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York, USA.
Dicken
Cary
C
Lustbader
Joyce W
JW
Tortoriello
Drew V
DV
D000328:Adult; D054304:Anti-Mullerian Hormone / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D019898:Autocrine Communication / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004717:Endometrium / Q000378:metabolism* / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D019899:Paracrine Communication / Q000235:genetics / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection
D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; C084621:anti-Mullerian hormone receptor; D011374:Progesterone; D004958:Estradiol; D054304:Anti-Mullerian Hormone