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Biology of Reproduction 62, 655-663 (2000)
© 2000 Society for the Study of Reproduction, Inc.


Articles

A Putative Stimulatory Role of Progesterone Acting via Progesterone Receptors in the Steroidogenic Cells of the Human Corpus Luteum1

Ulrika Ottandera, Kenichi Hosokawaa, Kui Liub, Anders Berghc, Tor Nyb, and Jan I. Olofsson2,a

a Departments of Obstetrics and Gynecology, b Medical Biochemistry and Biophysics, and c Pathology, Umeå University, S-901 87 Umeå, Sweden

To further explore the proposed auto-regulatory role of progesterone action in the human corpus luteum (CL), the expression and functional roles of progesterone receptor (PR) isoforms A and B during the luteal phase (LP) of the menstrual cycle were investigated. A total of 27 otherwise healthy patients previously scheduled for surgery were recruited after informed consent. An LH rise was detected, and CL were grouped according to age (Days 2–5 post-LH-rise, early LP; Days 6–10, mid LP; Days 11–14, late LP). Using a semiquantitative reverse transcription-polymerase chain reaction assay, the PR-B mRNA levels, which were 100- to 1000-fold lower than PR-A/B mRNA, were 46% lower (P < 0.05, n = 24) in mid LP, compared to early and late LP. CL tissue levels of progesterone and PR-A/B protein levels were inversely correlated to increasing CL age; i.e., significantly reduced levels were observed in the late LP (r2 = 0.34, P < 0.01, n = 23). Expression of PR-A/B mRNA as well as PR-A/B protein were detected by in situ hybridization and immunohistochemistry, respectively. Both methods revealed a clear and distinct localization to cells in the steroidogenic layer of the CL. Freshly obtained mid-luteal CL cells were cultured in vitro, and media were analyzed for progesterone concentrations after treatment by incremental doses of hCG and the stable PR antagonist mifepristone, alone or in combination. Mifepristone did not per se alter progesterone synthesis, but when it was added in conjunction with hCG, a dose-related inhibitory response was seen, with a maximal 47% reduction in progesterone output at a 10 µM addition (P < 0.05, n = 3). Collectively, these data implicate a stimulatory role of progesterone receptor-mediated action in the steroidogenic cells of the human CL, which may serve as an important pathway for maintaining functional homeostasis during early pregnancy.

First decision: 5 August 1999.

1 Supported by grants from The Swedish Medical Research Council K99-72X-13144-01A and K98-17P-11832-03C (J.I.O.) and by the Cancer Research Foundation of the Department of Oncology at Umeå University, The Swedish Society of Medicine, and The Swedish Society for Medical Research.

2 Correspondence. FAX: 46 90 773905; jan.olofsson{at}obstgyn.umu.se




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