In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development

Goto, Masahiro

doi:10.1172/jci25091

Cited by 248 publications

(242 citation statements)

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“…On the other hand, the expression of NGFIB was inversely correlated with the ability of the tissues to produce DHEA [39]. This inverse correlation between adrenal androgen production and the expression of NGFIB and HSD3B2 appears to be a unifying link for the production of DHEA by the fetal adrenal and adult adrenal reticularis as postulated by Goto et al [40].…”

Section: ) 3β-hydroxysteroid Dehydrogenase Type 2 (Hsd3b2)mentioning

confidence: 61%

Regulation of the adrenal androgen biosynthesis

Rainey

Nakamura

2008

The Journal of Steroid Biochemistry and Molecular Biology

145

107

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The human adrenal reticularis produces the so-called adrenal androgens, dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S). As opposed to the cortisol and aldosterone little is known regarding the mechanisms that regulate the production of the adrenal androgens. Several recent studies have shown that type II 3β-hydroxysteroid dehydrogenase (HSD3B2), cytochrome b5 (CYB5), and steroid sulfotransferase (SULT2A1) play an important role in the regulation of adrenal androgen production. Specifically, adrenal production of DHEA-S is correlated with reticularis expression of SULT2A1 and CYB5. In contrast, HSD3B2 has an inverse correlation with adrenal androgen production likely due to its unique ability to remove precursors from the pathway leading to DHEA. Therefore, its expression is limited to the adrenal glomerulosa/fasciculata but not in reticularis. The differential expression of these three proteins appears to be critical for reticularis function. In this review, we focus on studies that have begun to define the mechanisms regulating the transcription of these genes. Understanding the mechanisms controlling differential expression of these proteins should provide novel information about the human adrenal reticularis and its production of DHEA and DHEA-S. KeywordsAdrenal; Androgen; Cytochrome b5; DHEA-sulfotransferase; 3β-hydroxysteroid dehydrogenase II. Background & SignificanceThe fetal adrenal produces large amounts of dehydroepiandrosterone (DHEA) and DHEAsulfate (DHEAS) during fetal development (Fig. 1). DHEA-S concentrations are also high in the newborn (Fig. 1) [1]. However, by age 1, the specialized fetal zone is lost and replaced by the definitive adrenal cortex, which initially synthesizes little DHEA-S (Fig. 1). Hence, DHEA-S production declines precipitously during the first months of life and remains low until adrenarche commences at about age 6-8 [2]. This rise in the circulating concentrations of DHEA and DHEA-S is the biochemical hallmark of adrenarche [3]. Importantly, the rise in DHEA-S occurs prior to the increase of either estrogens or androgens associated with puberty [4]. Circulating DHEA-S concentrations continue to rise and peak during the second decade of life, with levels being higher in males than in females (Fig. 1) [3,5]. While circulating concentrations of DHEA and DHEA-S rise progressively in adrenarche, cortisol and ACTH concentrations do not change significantly in this period, indicating that adrenarche is not simply a global activation of the pituitary-adrenal axis.Correspondence and reprint requests addressed to: William E Rainey, Ph.D. Department of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912,, Email: E-mail: wrainey@mcg.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its f...

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Section: ) 3β-hydroxysteroid Dehydrogenase Type 2 (Hsd3b2)mentioning

confidence: 61%

Regulation of the adrenal androgen biosynthesis

Rainey

Nakamura

2008

The Journal of Steroid Biochemistry and Molecular Biology

145

107

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“…These results strengthen the notion that glucocorticoids are potent negative regulators of beta cell development and function in mice. Moreover, it suggests that humans who received dexamethasone treatment during fetal life in specific situations such as prevention of ambiguous genitalia in congenital adrenal hyperplasia syndrome [22] may undergo altered beta cell development, inasmuch as both the production of cortisol de novo by the human fetus and the expression of the GR in the human fetal pancreas occur at exactly the same time as pancreatic progenitors are committing to the endocrine lineage [23,24]. These individuals treated in utero with glucocorticoids may consequently be at increased risk of developing diabetes later in life and should therefore be followed closely.…”

Section: Discussionmentioning

confidence: 99%

Genetic evidence of the programming of beta cell mass and function by glucocorticoids in mice

et al. 2010

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Aims/hypothesis Prenatal exposure to excess glucocorticoids associates with low birthweight in rodents, primates and humans and its involvement in programming glucose homeostasis is suspected. Our aim was to further dissect the role of glucocorticoids on beta cell development and function in mice. Methods Using the model of maternal general food restriction during the last week of pregnancy, we thoroughly studied in the CD1 mouse-mothers and fetal and adult offspring-the pancreatic, metabolic and molecular consequences of maternal undernutrition associated with excess glucocorticoids. The specific involvement of the glucocorticoid receptor (GR) was studied in mutant fetuses lacking GR in pancreatic precursors or mature beta cells. Results Maternal general food restriction in the mouse is associated with decreased maternal glucose and increased corticosterone levels. Fetuses from underfed dams had increased corticosterone levels, decreased pancreatic endocrine gene expression but increased exocrine gene expression and a lower beta cell mass. The offspring of these dams had a low birthweight, permanent postnatal growth retardation and, as adults, impaired glucose tolerance, decreased beta cell mass (−50%) and massively reduced islet expression (−80%) of most of the genes involved in beta cell function (e.g. Pdx1, Sur1 [also known as Abcc8], insulin). Moreover, using mutant fetuses lacking GR in pancreatic precursors or beta cells we show that the deleterious effect of undernutrition on fetal beta cell development requires the presence of the GR in pancreatic precursor cells. Conclusions/interpretation These results demonstrate the crucial role of excess fetal glucocorticoids and the importance of GR signalling in progenitor cells to programme beta cell mass and dysfunction.

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“…They are "Fetal Zone" (FZ), "Transitional Zone" (TZ), "Definitive Zone" (DZ) and finally "fetal adrenal capsule" (C) [21]. Activation of HPA axis leads to Fetal Zone Enlargement (FZE) and secretion of DehydroepinadrosteroneSulfate (DHEA-S).…”

Section: Cervical Elastographymentioning

confidence: 99%

Role of Imaging and its Advances in Prediction of Preterm Birth

Agarwal

2017

IJRRT

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Preterm Birth (PTB) is one of the leading causes of neonatal mortality and morbidity worldwide, compared to the term deliveries. The survivors come across long term morbidity in the form of sensory, motor, cognitive and behavioral deficits. Hence, accurate and early prediction of the preterm is important for timely intervention and prevention of the fetal outcome. Contemporary method of assessment relies on the clinical and radiological signs, however still the rate of PTB is nearly constant over the years. This review discusses the role of various Ultrasonographic (USG) parameters & advances in prediction of PTB; based on the current medical literature.

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In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development

Cited by 248 publications

References 44 publications

Regulation of the adrenal androgen biosynthesis

Regulation of the adrenal androgen biosynthesis

Genetic evidence of the programming of beta cell mass and function by glucocorticoids in mice

Role of Imaging and its Advances in Prediction of Preterm Birth

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