Adrenal Androgens and Androgen Precursors—Definition, Synthesis, Regulation and Physiologic Actions

Turcu, Adina F.; Smith, Joshua M.; Auchus, Richard J.; Rainey, William E.

doi:10.1002/cphy.c140006

Cited by 98 publications

(68 citation statements)

References 201 publications

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“…In agreement with the migration model, the cell proliferation index is highest in the outer ZG of human adrenal tissues from early infancy to late puberty [8]. Genes encoding a number of transcription and growth factors as well as polypeptide hormones have been linked to adrenocortical cell development and to modulation of steroidogenic function [6, 8-11]. However, the exact molecular mechanisms governing human adrenal zonation and ZR development remain poorly understood.…”

Section: Introductionmentioning

confidence: 76%

“…The coexpression of 3βHSD2 and P450c17 along with P450c11 in the ZF results in the production of cortisol under the influence of ACTH. By contrast, the ZR expresses relatively very little 3βHSD2 and large amounts of P450c17 and cytochrome b5, which selectively activate the 17,20- lyase activity of P450c17 and DHEA-sulfotransferase (SULT2A1) [6, 13]. Consequently, the C19 steroid DHEA is produced, much of which is sulfated to DHEAS [6, 13].…”

Section: Functional Zonation Of the Human Adrenal Cortexmentioning

confidence: 99%

“…By contrast, the ZR expresses relatively very little 3βHSD2 and large amounts of P450c17 and cytochrome b5, which selectively activate the 17,20- lyase activity of P450c17 and DHEA-sulfotransferase (SULT2A1) [6, 13]. Consequently, the C19 steroid DHEA is produced, much of which is sulfated to DHEAS [6, 13]. This Δ 5 pathway is the preferred route to C19 steroid production in humans as the 17,20-lyase activity of human P450c17 does not efficiently convert 17α-hydroxyprogesterone (17OHP) to androstenedione (A4) [6, 13].…”

Section: Functional Zonation Of the Human Adrenal Cortexmentioning

confidence: 99%

“…In pre-adrenarche children, the zona glomerulosa (ZG) and the zona fasciculata (ZF) are clearly present but only focal islands of reticularis cells, insufficient to influence serum DHEAS levels, can be identified. Adrenal production of DHEA and DHEAS resumes at adrenarche (ages 6–8 years) when a continuous layer of reticularis cells develops and thickens forming the zona reticularis (ZR) [1, 4-6]. Peak levels of DHEA and DHEAS occur between ages 20 and 25 and decline thereafter.…”

Section: Introductionmentioning

confidence: 99%

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Human Adrenal Cortex: Epigenetics and Postnatal Functional Zonation

Baquedano¹,

Belgorosky²

2018

Horm Res Paediatr

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The human adrenal cortex, involved in adaptive responses to stress, fluid homeostasis, and secondary sexual characteristics, arises from a tightly regulated development of a zone and cell type-specific secretory pattern. However, the molecular mechanisms governing adrenal zonation, particularly postnatal zona reticularis development, which produce adrenal androgens in a lifetime-specific manner, remain poorly understood. Epigenetic events, including DNA and histone modifications as well as regulation by noncoding RNAs, are crucial in establishing or maintaining the expression pattern of specific genes and thus contribute to the stability of a specific differentiation state. Emerging evidence points to epigenetics as another regulatory layer that could contribute to establishing the adrenal zone-specific pattern of enzyme expression. Here, we outline the developmental milestones of the human adrenal cortex, focusing on current advances and understanding of epigenetic regulation of postnatal functional zonation. Numerous questions remain to be addressed emphasizing the need for additional investigations to elucidate the role of epigenetics in the human adrenal gland. Ultimately, improved understanding of the epigenetic factors involved in adrenal development and function could lead to novel therapeutic interventions.

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Section: Introductionmentioning

confidence: 76%

Section: Functional Zonation Of the Human Adrenal Cortexmentioning

confidence: 99%

Section: Functional Zonation Of the Human Adrenal Cortexmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Human Adrenal Cortex: Epigenetics and Postnatal Functional Zonation

Baquedano¹,

Belgorosky²

2018

Horm Res Paediatr

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“…Because five enzymatic steps are involved in cortisol biosynthesis, there are five distinct CAH syndromes [2]. Approximately 95 percent of cases are due to 21-hydroxylase deficiency [3].…”

Section: Introductionmentioning

confidence: 99%

Validation of a New RP-HPLC Method for Determination of Hydrocortisone Acetate Complexed with HPβCD in a Oral Liquid Pharmaceutical Preparation

RMS¹

2017

JAPLR

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A simple reversed-phase high-performance liquid chromatographic method (RP-HPLC) for the simultaneous determination of hydrocortisone acetate (HA) complexed with 2-hydroxypropyl-β-cyclodextrin (HPβCD), its degradation products and preservative in an oral liquid pharmaceutical preparation has been validated. The compounds were separated on a 150mm x 4.6mm C 18 column packed with 5μm particles and a 1mm x 4mm pre-column with heating at 30 °C. The mobile phase optimized was a mixture of methanol, acetonitrile and water 35:25:40 (v/v/v), pumped at a flow rate of 1.0mL min -1 . The validation data showed that the proposed method is simple, reliable, fast and has good robustness, specificity, linearity, precision and accuracy.

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Decamethylcyclopentasiloxane affects estradiol production in female rats but not H295R cells

Ogawa,

Kitamoto,

Takeda

et al. 2023

J of Applied Toxicology

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Sex hormones, such as androgens and estrogens, are predominantly produced in the gonads (ovaries and testes) and adrenal cortex. Endocrine‐disrupting chemicals (EDCs) are substances that mimic, block, or interfere with hormones in the endocrine systems of humans and organisms. EDCs mainly act via nuclear receptors and steroidogenesis‐related enzymes. In the OECD conceptual framework for testing and assessment of EDCs, several well‐known assays are used to identify the potential disruption of nuclear receptors both in vivo and in vitro, whereas the H295R steroidogenesis assay is the only assay that detects the disruption of steroidogenesis. Forskolin and prochloraz are often used as positive controls in the H295R steroidogenesis assay. Decamethylcyclopentasiloxane (D5) was suspected one of EDCs, but the effects of D5 on steroidogenesis remain unclear. To establish a short‐term in vivo screening method that detects the disruption of steroidogenesis, rats in the present study were fed a diet containing forskolin, prochloraz, or D5 for 14 days. Forskolin increased plasma levels of 17β‐estradiol (E2) and testosterone as well as the mRNA level of Cyp19 in both the adrenal glands and ovaries. Prochloraz induced the loss of cyclicity in the sexual cycle and decreased plasma levels of E2 and testosterone. D5 increased E2 levels and shortened the estrous cycle in a dose‐dependent manner; however, potential endocrine disruption was not detected in the H295R steroidogenesis assay. These results demonstrate the importance of comprehensively assessing the endocrine‐disrupting effects of chemicals on steroidogenesis in vivo.

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Adrenal Androgens and Androgen Precursors—Definition, Synthesis, Regulation and Physiologic Actions

Cited by 98 publications

References 201 publications

Human Adrenal Cortex: Epigenetics and Postnatal Functional Zonation

Human Adrenal Cortex: Epigenetics and Postnatal Functional Zonation

Validation of a New RP-HPLC Method for Determination of Hydrocortisone Acetate Complexed with HPβCD in a Oral Liquid Pharmaceutical Preparation

Decamethylcyclopentasiloxane affects estradiol production in female rats but not H295R cells

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