Mitochondrial 3 beta-hydroxysteroid dehydrogenase (HSD) is essential for the synthesis of progesterone by corpora lutea:
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BioMed Central
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Hypothesis
Mitochondrial 3 beta-hydroxysteroid dehydrogenase (HSD) is essential for the synthesis of progesterone by corpora lutea: An hypothesis John C Chapman1, Jose R Polanco1,2, Soohong Min1 and Sandra D Michael*1 Address: 1Department of Biological Sciences, Binghamton University, Binghamton, NY 13902-6000, USA and 2Notre Dame Ambulatory Care Center, Medical Director, 1000 Broad Street, Central Falls, RI 02863, USA Email: John C Chapman - [email protected]; Jose R Polanco - [email protected]; Soohong Min - [email protected]; Sandra D Michael* - [email protected] * Corresponding author
Published: 03 April 2005 Reproductive Biology and Endocrinology 2005, 3:11
doi:10.1186/1477-7827-3-11
Received: 12 January 2005 Accepted: 03 April 2005
This article is available from: http://www.rbej.com/content/3/1/11 © 2005 Chapman et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract In mouse ovaries, the enzyme 3 beta-hydroxysteroid dehydrogenase (HSD) is distributed between microsomes and mitochondria. Throughout the follicular phase of the estrous cycle, the HSD activity in microsomes is predominant; whereas, after LH stimulation, HSD activity during the luteal phase is highest in the mitochondria. The current study examined whether or not LH stimulation always results in an increase in mitochondrial HSD activity. This was accomplished by measuring the HSD activity in microsomal and mitochondrial fractions from ovaries of pregnant mice. These animals have two peaks of LH during gestation, and one peak of LH after parturition. It was found that mitochondrial HSD activity was highest after each peak of LH. It is proposed that mitochondrial HSD is essential for the synthesis of high levels of progesterone. The increase in HSD activity in mitochondria after LH stimulation occurs because: 1) LH initiates the simultaneous synthesis of HSD and the cholesterol side-chain cleavage enzyme (P450scc); and, 2) HSD and P450scc bind together to form a complex, which becomes inserted into the inner membrane of the mitochondria. High levels of progesterone are synthesized by mitochondrial HSD because: 1) the requisite NAD+ cofactor for progesterone synthesis is provided directly by the mitochondria, rather than indirectly via the rate limiting malate-aspartate shuttle; and, 2) the end-product inhibition of P450scc by pregnenolone is eliminated because pregnenolone is converted to progesterone.
Background With the exception of 3β-hydroxysteroid dehydrogenase (HSD), the enzymes involved in the conversion of cholesterol to steroid hormones are located in either the mitochondria or the endoplasmic reticulum. HSD is unique in that it is located in both subcellular organelles. In either location, HSD converts pregnenolone and dehydroepiando
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