Production of interleukin-1alpha by human endometrial stromal cells is triggered during menses and dysfunctional bleeding and is induced in culture by epithelial interleukin-1alpha released upon ovarian steroids withdrawal.

Context: Endometrial breakdown during menstruation and dysfunctional bleeding is triggered by the abrupt expression of matrix metalloproteinases (MMPs), including interstitial collagenase (MMP-1). The paracrine induction of MMP-1 in stromal cells via epithelium-derived IL-1alpha is repressed by ovarian steroids. However, the control by estradiol (E) and progesterone (P) of endometrial IL-1alpha expression and bioactivity remains unknown.

Opposite regulation of transforming growth factors-beta2 and -beta3 expression in the human endometrium.

TGF-betas have been reported to mediate the repression by progesterone of several matrix metalloproteinases in the human endometrium, thereby preventing menstrual breakdown. Because of conflicting reports on the expression profiles, source, and regulation of the TGF-beta system in this tissue, we investigated by real-time RT-PCR and ELISA the expression of the three TGF-betas (total and mature forms) and their two receptors throughout the menstrual cycle, and their regulation by ovarian steroids in cultured explants including their microdissected epithelial and stromal compartments. Regulation by cAMP and MAPK was further investigated.

Response of matrix metalloproteinases and tissue inhibitors of metalloproteinases messenger ribonucleic acids to ovarian steroids in human endometrial explants mimics their gene- and phase-specific differential control in vivo.

Context: Cyclic remodeling and breakdown of the extracellular matrix, a unique feature of the human endometrium, depends on matrix metalloproteinases (MMPs). These enzymes are globally controlled by estradiol and progesterone or their withdrawal, but various MMPs and their tissue inhibitors (TIMPs) show distinct responses.

Objective And Design: To clarify the role of ovarian steroids in the differential regulation of MMP-1, MMP-3, MMP-7, MMP-8, MMP-10, TIMP-1, TIMP-2, and TIMP-3 mRNAs, we compared their variations in the cycling endometrium in vivo with their response to hormone addition or withdrawal in corresponding explants.

Regulation of matrix metalloproteinase-9/gelatinase B expression and activation by ovarian steroids and LEFTY-A/endometrial bleeding-associated factor in the human endometrium.

Various matrix metalloproteinases (MMPs) participate in the menstrual breakdown of the human endometrium. MMP-9/gelatinase B is proposed as a major factor because it degrades many extracellular matrix constituents, including in the vasculature. Although globally under ovarian steroids control, endometrial MMP-9 seems expressed differently than other MMPs, and conflicting publications prevent a clear understanding of its regulation.

Regulation and function of LEFTY-A/EBAF in the human endometrium. mRNA expression during the menstrual cycle, control by progesterone, and effect on matrix metalloprotineases.

The human endometrium is a unique tissue that is periodically shed during menstruation. Although overall triggered by ovarian steroids withdrawal, menstrual induction of matrix metalloproteinases (MMPs) and resulting tissue breakdown are focal responses, pointing to additional local modulators. LEFTY-A, a novel member of the transforming growth factor-beta family identified originally as an endometrial bleeding-associated factor (EBAF), is a candidate for this local control.

Circulating ovarian steroids and endometrial matrix metalloproteinases (MMPs).

Recent studies strongly suggest that matrix metalloproteinases (MMPs) play a key role in the initiation of menstrual bleeding in the human endometrium upon the fall of ovarian steroid serum concentrations by inducing the degradation of the extracellular matrix of this mucosa. MMPs are also involved in abnormal endometrial bleeding and have been identified in endometriotic foci. In all cases, they are associated with areas of extracellular matrix breakdown.