Endocrine Abstracts (2006) 11 OC14

Endometrial intracrinology: Expression of 3β-hydroxysteroid dehydrogenase (3βHSD), and 17β-hydroxysteroid dehydrogenase type 5 (17βHSD-5)

SE McDonald, JI Mason & HOD Critchley

Centre for Reproductive Biology, University of Edinburgh, Edinburgh, United Kingdom.

Introduction: 3βHSD catalyses the formation of Δ4-3-ketosteroids including progesterone and androgens. Levonorgestrel (LNG) is an androgenic progestogen used in the LNG intra-uterine system (LNG-IUS). 17βHSD-5 is involved not only in androgen and oestrogen metabolism, but also has 3β-reductase activity.

Objective: To determine expression patterns of 3βHSD-1 and -2, and 17βHSD-5 in human endometrium across the normal menstrual cycle and in endometrium exposed to intrauterine delivery of LNG (LNG-IUS).

Methods: Local ethical approval and informed consent were obtained. Endometrial biopsies were collected with a pipelle-endometrial-sampling device or at hysterectomy. RNA expression was studied by quantitative real-time PCR using specific and validated primers and probes for 3βHSD-1, 3βHSD-2 and 17βHSD-5. Protein expression and localisation were detected using antibodies against 3βHSD-1 (rabbit polyclonal, also detects 3βHSD-2) and 17βHSD-5 (mouse monoclonal).

Results: Neither 3βHSD-1 or -2 mRNA were detectable in normal endometrium. 3βHSD-1 transcript was expressed in endometrium exposed to intrauterine LNG. 3βHSD protein was observed at low levels in the glandular and surface epithelium of normal endometrium, and at greater levels in glands, stroma and surface epithelium endometrium exposed to LNG. 17βHSD-5 mRNA was expressed across the menstrual cycle, with levels greatest in the early secretory phase. Levels were low in endometrium exposed to LNG. 17βHSD-5 protein was expressed in the glandular and surface epithelium endometrium exposed to LNG, and strongly in endothelial cells of the endometrium throughout the menstrual cycle.

Summary: 3βHSD-1 mRNA and protein expression is upregulated in endometrium exposed to exogenous LNG, potentially due to the androgenic effects of LNG. On the other hand an intracrine role for 17βHSD-5 is implicated in oestradiol synthesis and subsequent action in the endometrial vascular endothelial cells.

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