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The steroid metabolome and transcrip...

Rege, Juilee.

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The steroid metabolome and transcriptome of the human adrenal gland.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The steroid metabolome and transcriptome of the human adrenal gland./
Author:	Rege, Juilee.
Description:	270 p.
Notes:	Source: Dissertation Abstracts International, Volume: 75-07(E), Section: B.
Contained By:	Dissertation Abstracts International75-07B(E).
Subject:	Biology, Physiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3580217
ISBN:	9781303892882

The steroid metabolome and transcriptome of the human adrenal gland.
Rege, Juilee.

The steroid metabolome and transcriptome of the human adrenal gland. - 270 p.

Source: Dissertation Abstracts International, Volume: 75-07(E), Section: B.

Thesis (Ph.D.)--Georgia Regents University, 2014.

This item is not available from ProQuest Dissertations & Theses.

The adrenal glands serve as multifunctional endocrine organs which are anatomically and functionally divided into three concentric zones, namely the zona glomerulosa (ZG), zona fasciculata (ZF) and zona reticularis (ZR). The human ZR is considered the primary source for the C19 steroids like dehydroepiandrostenedione (DHEA) and DHEA sulfate (DHEAS), which have little direct activity on the androgen receptor but can act as precursors for more potent androgens. Adrenal-derived C19 steroids are significant contributors to circulating androgens in women and in pre-pubertal children. The ZR remains dormant until around 6 years of age, after which it expands and produces increasing amounts of DHEA and DHEAS. This phenomenon is known as adrenarche. ACTH has been the accepted primary (but not the sole) mediator of adrenal C19 steroid biosynthesis, and thus adrenarche. We also speculate that other fine-tuning mechanisms might also play important roles in the physiologic production of adrenal C19 steroids. The goal of our ongoing studies was to determine the ability of the human adrenal to synthesize active androgens, as well as to further define the mechanisms regulating adrenal C19 steroid biosynthesis. In this dissertation, I will summarize my studies aimed at defining the adrenal C19 steroid metabolome and the transcriptome of the two adrenocortical zones, ZF and ZR. In addition, I will describe the novel findings that demonstrate bone morphogenetic protein-4 (BMP4) as a paracrine negative regulator of adrenal C19 steroid secretion.

ISBN: 9781303892882Subjects--Topical Terms:

1017816
Biology, Physiology.

The steroid metabolome and transcriptome of the human adrenal gland.
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020 $a 9781303892882
035 $a (MiAaPQ)AAI3580217
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100 1 $a Rege, Juilee. $3 3170759
245 1 4 $a The steroid metabolome and transcriptome of the human adrenal gland.
300 $a 270 p.
500 $a Source: Dissertation Abstracts International, Volume: 75-07(E), Section: B.
500 $a Adviser: William E. Rainey.
502 $a Thesis (Ph.D.)--Georgia Regents University, 2014.
506 $a This item is not available from ProQuest Dissertations & Theses.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a The adrenal glands serve as multifunctional endocrine organs which are anatomically and functionally divided into three concentric zones, namely the zona glomerulosa (ZG), zona fasciculata (ZF) and zona reticularis (ZR). The human ZR is considered the primary source for the C19 steroids like dehydroepiandrostenedione (DHEA) and DHEA sulfate (DHEAS), which have little direct activity on the androgen receptor but can act as precursors for more potent androgens. Adrenal-derived C19 steroids are significant contributors to circulating androgens in women and in pre-pubertal children. The ZR remains dormant until around 6 years of age, after which it expands and produces increasing amounts of DHEA and DHEAS. This phenomenon is known as adrenarche. ACTH has been the accepted primary (but not the sole) mediator of adrenal C19 steroid biosynthesis, and thus adrenarche. We also speculate that other fine-tuning mechanisms might also play important roles in the physiologic production of adrenal C19 steroids. The goal of our ongoing studies was to determine the ability of the human adrenal to synthesize active androgens, as well as to further define the mechanisms regulating adrenal C19 steroid biosynthesis. In this dissertation, I will summarize my studies aimed at defining the adrenal C19 steroid metabolome and the transcriptome of the two adrenocortical zones, ZF and ZR. In addition, I will describe the novel findings that demonstrate bone morphogenetic protein-4 (BMP4) as a paracrine negative regulator of adrenal C19 steroid secretion.
520 $a Although there is overall agreement that the adrenal is a key provider of androgens in women, the overall adrenal C19 steroid metabolome and its responsiveness to ACTH has not been well studied. We used LC-MS/MS to quantify nine unconjugated C19 steroids and two estrogens in human adrenal vein (AV) samples, pre and post ACTH stimulation. DHEAS was quantified by RIA. LC-MS/MS profiling of AV samples from women demonstrated that AV levels of DHEAS, before and after ACTH infusion, are the highest among the steroids measured. Of the unconjugated steroids, 11 OHA, DHEA and A4 are the most abundant in AV samples, pre and post ACTH stimulation. The study also demonstrated that the adrenal gland can synthesize potent C19 steroids like testosterone and 11beta-hydroxytestosterone (11OHT). We propose that 11OHT could represent a novel adrenal androgen biomarker because its synthesis requires the enzyme CYP11B1, which is expressed solely in the adrenal cortex. Based on the current study involving LC-MS/MS, measurements of various C 19 steroids and a microarray profile of the different adrenal steroidogenic enzymes, we provided evidence of a novel pathway in the human adrenal leading to the production of several androgens and precursor steroids.
590 $a School code: 1749.
650 4 $a Biology, Physiology. $3 1017816
650 4 $a Biology, Endocrinology. $3 1682242
650 4 $a Chemistry, Biochemistry. $3 1017722
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710 2 $a Georgia Regents University. $3 3170760
773 0 $t Dissertation Abstracts International $g 75-07B(E).
790 $a 1749
791 $a Ph.D.
792 $a 2014
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3580217