Luteal Lipid Droplets: A Novel Platform for Steroid Synthesis

Author:

Plewes Michele R123ORCID,Talbott Heather A1,Saviola Anthony J4,Woods Nicholas T5,Schott Micah B3,Davis John S123

Affiliation:

1. Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE 68198-3255 , USA

2. Department of Research Services, Veterans Affairs Nebraska Western Iowa Health Care System , Omaha, NE 68105 , USA

3. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870 , USA

4. Department of Biochemistry and Molecular Genetics, University of Colorado , Aurora, CO 80045 USA

5. Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center , Omaha, NE 68198-6805 , USA

Abstract

Abstract Progesterone is an essential steroid hormone that is required to initiate and maintain pregnancy in mammals and serves as a metabolic intermediate in the synthesis of endogenously produced steroids, including sex hormones and corticosteroids. Steroidogenic luteal cells of the corpus luteum have the tremendous capacity to synthesize progesterone. These specialized cells are highly enriched with lipid droplets that store lipid substrate, which can be used for the synthesis of steroids. We recently reported that hormone-stimulated progesterone synthesis by luteal cells requires protein kinase A–dependent mobilization of cholesterol substrate from lipid droplets to mitochondria. We hypothesize that luteal lipid droplets are enriched with steroidogenic enzymes and facilitate the synthesis of steroids in the corpus luteum. In the present study, we analyzed the lipid droplet proteome, conducted the first proteomic analysis of lipid droplets under acute cyclic adenosine monophosphate (cAMP)-stimulated conditions, and determined how specific lipid droplet proteins affect steroidogenesis. Steroidogenic enzymes, cytochrome P450 family 11 subfamily A member 1 and 3 beta-hydroxysteroid dehydrogenase (HSD3B), were highly abundant on lipid droplets of the bovine corpus luteum. High-resolution confocal microscopy confirmed the presence of active HSD3B on the surface of luteal lipid droplets. We report that luteal lipid droplets have the capacity to synthesize progesterone from pregnenolone. Lastly, we analyzed the lipid droplet proteome following acute stimulation with cAMP analog, 8-Br-cAMP, and report increased association of HSD3B with luteal lipid droplets following stimulation. These findings provide novel insights into the role of luteal lipid droplets in steroid synthesis.

Funder

Agriculture and Food Research Initiative Competitive

National Institute of Food and Agriculture

US Department of Veterans Affairs

National Institutes of Health

The Olson Center for Women’s Health

VA Senior Research Career Scientist Award

Publisher

The Endocrine Society

Subject

Endocrinology

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