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Hum. Reprod. Advance Access published online on October 27, 2005
Human Reproduction, doi:10.1093/humrep/dei373
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received May 31, 2005
Revised August 6, 2005
Accepted August 10, 2005

Article

The post-menopausal ovary displays a unique pattern of steroidogenic enzyme expression

Jon C. Havelock 1, William E. Rainey 1, Karen D. Bradshaw 1, and Bruce R. Carr 1*

1 Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas, 75390 USA

* To whom correspondence should be addressed.
Bruce R. Carr, E-mail: Bruce.Carr{at}utsouthwestern.edu


  Abstract

BACKGROUND: While menopause results in the loss of cyclic steroid production, evidence exists for persistent, albeit reduced, ovarian androgen production. In order to continue to synthesize ovarian androgens, the steroidogenic enzymes necessary for androgen biosynthesis must be present. Few studies have selectively analysed some of the steroidogenic enzymes present in the post-menopausal ovary (PMO), and a comprehensive study of this matter has never been undertaken. METHODS: RNA and protein were obtained from PMO, pre-menopausal ovarian stroma, corpora lutea (CL), ovarian follicles, placenta, and myometrium. Oligonucleotide microarray analysis was performed to compare the gene expression profiles of PMO with pre-menopausal ovarian stroma. Real-time RT-PCR was performed for LH/HCG receptor (LHCGR), steroidogenic acute regulatory (StAR), cholesterol side-chain cleavage (CYP11A), 3{beta}-hydroxysteroid dehydrogenase type I (HSD3B1) and type II (HSD3B2, 3{beta}HSD), 17{alpha}-hydroxylase (CYP17), cytochrome b5 (CytB5), and aromatase (CYP19). Western blot analysis was performed for StAR, CYP11A, CYP17,and 3{beta}HSD. RESULTS: The PMO and pre-menopausal ovarian stroma had a similar pattern of steroidogenic enzyme expression. The PMO had persistent, but reduced, levels of LHCGR and most steroidogenic enzymes. CYP19 and HSD3B2 mRNA were greatly reduced in PMO in comparison with CL (50-fold and 2000-fold less respectively). HSD3B2 was not detectable in PMO by western analysis. CONCLUSIONS: This study supports the idea that the PMO retains some steroidogenic capacity. However, based on steroidogenic enzyme expression, the PMO has a unique pattern of steroidogenic enzyme expression that favors {Delta}5 steroid formation over {Delta}4 steroid formation.

Keywords: HCG/ovary/post-menopausal/steroids.
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