The decidualizing effect of progesterone may involve direct transcriptional activation of corticotrophin-releasing hormone from human endometrial stromal cells

The hypothalamic neuropeptide corticotrophin-releasing hormone (CRH) is als o produced by human endometrial cells and is directly involved in the decid ualization process as a paracrine inducer. The aim of the present work was to examine the effect of progesterone, the main decidualizing factor, on en dometrial CRH, in primary cultures of human endometrial stromal cells. The effect of progesterone was examined by measuring the effects of medroxyprog esterone acetate (MPA) on (i) the concentration of immunoreactive CRH in is olated human endometrial stromal cells and (ii) the activity of the CRH pro moter in human endometrial stromal cells transfected with a 0.9 kb fragment of the 5'-flanking region of the human CRH gene coupled to luciferase repo rter. The data show that MPA increased the production and secretion of immu noreactive CRH from stromal cells and induced the activity of the CRH promo ter, both in a dose-dependent manner. These effects were partially reversed by a molar excess of the antiprogestin RU 486 and were completely abolishe d in the presence of 100 nmol/l of the cAMP inhibitor, Rp-cAMP. The effect of progesterone on the CRH promoter requires the existence of an intact CRH sequence since experiments carried out with a deleted palindromic cAMP res ponse element (CRE: 5'-TGACGTCA) at -224 bp of the CRH promoter resulted in a complete loss of MPA effect. In conclusion, these data provide evidence that progesterone induces the transcription of CRH gene in human endometria l stroma. This effect coupled with the decidualizing properties of progeste rone and CRH may indicate that progesterone and CRH form a decidualizing lo cal pathway within the human endometrium.