21-Hydroxylase-Derived Steroids in Follicles of Nonobese Women Undergoing Ovarian Stimulation for In Vitro Fertilization (IVF) Positively Correlate With Lipid Content of Luteinized Granulosa Cells (LGCs) as a Source of Cholesterol for Steroid Synthesis

Author:

Amin Marli1,Simerman Ariel1,Cho Michele1,Singh Prapti1,Briton-Jones Christine2,Hill David2,Grogan Tristan3,Elashoff David3,Clarke Nigel J.4,Chazenbalk Gregorio D.1,Dumesic Daniel A.1

Affiliation:

1. Department of Obstetrics and Gynecology (M.A., A.S., M.C., P.S., G.D.C., D.A.D.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90024;

2. ART Reproductive Center (C.B.-J., D.H.), Beverly Hills, California 90210

3. Department of Medicine Statistics Core (T.G., D.E.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, Los Angeles, California 90095;

4. Quest Diagnostics Nichols Institute (N.J.C.), San Juan Capistrano, California 92675;

Abstract

Context: Mineralocorticoid synthesis by the nonhuman primate periovulatory follicle enhances luteinization. Whether a similar event occurs in women undergoing in vitro fertilization (IVF) is unknown. Objective: The objective of the study was to determine whether human luteinized granulosa cells (LGCs) produce mineralocorticoids derived from 21-hydroxylase activity and also express mRNA for 21-hydroxylase and the mineralocorticoid receptor. Design: This was a prospective cohort study. Setting: The study was conducted at an academic center. Patients: LGC lipid content and follicle fluid (FF) hormone analysis was performed on 27 nonobese IVF women. LGCs from six additional nonobese IVF women were used for gene expression studies. Intervention: At oocyte retrieval, FF was aspirated from the first follicle (≥16 mm in size) of each ovary and pooled LGCs were collected. Main Outcome Measures: FF steroid analysis was performed by liquid chromatography-tandem mass spectrometry. LGCs were stained with lipid fluorescent dye BODIPY FL C16 to estimate lipid content by confocal microscopy as a cholesterol source for steroidogenesis in vivo. Quantitative real-time PCR was performed using LGCs to detect 21-hydroxylase and mineralocorticoid receptor mRNA expression. Pearson correlation coefficients determined associations between FF steroid levels and LGC lipid content. Results: FF levels of the 21-hydroxylase-derived steroids, 11-deoxycorticosterone [DOC, 39.97, median (13.94–63.02) ng/mL] and 11-deoxycortisol [11DOC, 2.07 (0.69–5.01) ng/mL], along with the 21-hydroxylase precursor 17-hydroxyprogesterone [1268.21 (493.26–3558.39) ng/mL], positively correlated with LGC lipid content (84 ± 43 fluorescent units/sample) (P ≤ .05, all steroids). 21-Hydroxylase and mineralocorticoid receptor mRNA expression was detected in LGCs. Conclusions: Human LGCs likely synthesize 21-hydroxylase-derived mineralocorticoids from cholesterol-containing lipid in vivo to promote postovulatory luteinization via mineralocorticoid receptor-mediated events.

Publisher

The Endocrine Society

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3