Endocrine Abstracts (2003) 6 OC5

Non-genomic Progesterone Receptors in Human Endometrium

OAK Harding1, TA Bramley1, HOD Critchley1, RW Kelly2 & HN Jabbour2


1Department of Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh, UK; 2MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, Edinburgh, UK.


Introduction:

Steroid hormones exert numerous effects through their action on genomic receptors but little is known about the rapid effects mediated via membrane-bound proteins. Analyses in several vertebrate species indicate that three groups (alpha or A, beta or B, and gamma) of membrane progestin receptors (mPR) exist and have distinct tissue distributions.

Objective:

The aims of this study were to establish the presence of an mPR in human endometrial tissue collected from various stages of the menstrual cycle and human endometrial fibroblast cells (primary cultures).

Methods:

Relative expression of mPR (isoforms A and B) mRNA across the menstrual cycle was measured by quantitative RT-PCR (Taqman) in early, mid-, and late stages of both the proliferative and secretory phases (n=48). Endometrial fibroblasts were homogenised and nuclear, membrane and cytosol fractions isolated by differential centrifugation. Fractions were assayed for binding of 3H-labelled progesterone in vitro. Ethical approval and informed consent was obtained for the study.

Results:

There was no significant variation between observed levels of mPRA expression. However there was a significant increase in mPRB (P<0.05) from the late proliferative to early secretory period. Radio-ligand binding assays showed highest progesterone binding in the microsomal fraction followed by the nuclear fraction. Little activity was present in the cytosol fraction. Binding to endometrial microsomes was displaceable by low levels (20nM) of progesterone, and at much higher concentrations (300-1000nM) testosterone and oestradiol. RU486 (an antagonist of the genomic PR) was unable to displace binding.

Conclusion:

High levels of progesterone-specific binding in membrane fractions of endometrial fibroblasts indicate the presence of a mPR. Both isoforms A and B of the putative mPR are expressed in the human endometrium at varying levels across the cycle. The nature of this variance and its role in mediating the non-genomic effects of progesterone remain to be further explored.

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