Temporal and spatial distribution of mast cells and steroidogenic enzymes in the human fetal adrenal

Naccache, Alexandre; Louiset, Estelle; Duparc, Céline; Laquerrière, Annie; Patrier, Sophie; Renouf, Sylvie; Gómez-Sánchez, Celso E.; Mukai, Kuniaki; Lefebvre, Henri; Castanet, Mireille

doi:10.1016/j.mce.2016.06.015

Cited by 25 publications

(23 citation statements)

References 47 publications

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“…In our studies, the enzymes necessary for adrenal steroid synthesis were expressed by week 12 of gestation and mostly at relatively high levels apart from HSD3B and CYP11B2 , which were low at this stage. Low levels of HSD3B and CYP11B2 transcripts in the late second/early third trimester have also been reported previously [ 9 , 30 ]. Despite low HSD3B transcript and protein expression, however, the Δ 4 steroids progesterone, 17α-hydroxyprogesterone and cortisol were present in significant amounts throughout the second trimester.…”

Section: Discussionsupporting

confidence: 80%

The human fetal adrenal produces cortisol but no detectable aldosterone throughout the second trimester

Johnston

Bellingham

Filis

et al. 2018

BMC Med

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BackgroundHuman fetal adrenal glands are highly active and, with the placenta, regulate circulating progesterone, estrogen and corticosteroids in the fetus. At birth the adrenals are essential for neonate salt retention through secretion of aldosterone, while adequate glucocorticoids are required to prevent adrenal insufficiency. The objective of this study was to carry out the first comprehensive analysis of adrenal steroid levels and steroidogenic enzyme expression in normal second trimester human fetuses.MethodsThis was an observational study of steroids, messenger RNA transcripts and proteins in adrenals from up to 109 second trimester fetuses (11 weeks to 21 weeks) at the Universities of Aberdeen and Glasgow. The study design was balanced to show effects of maternal smoking.ResultsConcentrations of 19 intra-adrenal steroids were quantified using liquid chromatography and mass spectrometry. Pregnenolone was the most abundant steroid while levels of 17α-hydroxyprogesterone, dehydroepiandrosterone sulphate (DHEAS) and progesterone were also high. Cortisol was present in all adrenals, but aldosterone was undetected and Δ4 androgens were low/undetected. CYP17A1, CYP21A2 and CYP11A1 were all highly expressed and the proteins localized to the adrenal fetal zone. There was low-level expression of HSD3B and CYP11B2, with HSD3B located mainly in the definitive zone. Maternal smoking altered fetal plasma adrenocorticotropic hormone (ACTH) (P = 0.052) and intra-adrenal progesterone, 17α-hydroxyprogesterone and 16α-hydroxyprogesterone, but not plasma or intra-adrenal cortisol, or intra-adrenal DHEAS. Fetal adrenal GATA6 and NR5A1 were increased by maternal smoking.ConclusionsThe human fetal adrenal gland produces cortisol but very low levels of Δ4 androgens and no detectable aldosterone throughout the second trimester. The presence of cortisol in fetal adrenals suggests that adrenal regulation of circulating fetal ACTH remains a factor in development of congenital adrenal hyperplasia during the second trimester, while a relative lack of aldosterone explains the salt-wasting disorders frequently seen in extreme pre-term neonates. Finally, maternal smoking may alter fetal adrenal sensitivity to ACTH, which could have knock-on effects on post-natal health.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1009-7) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 80%

The human fetal adrenal produces cortisol but no detectable aldosterone throughout the second trimester

Johnston

Bellingham

Filis

et al. 2018

BMC Med

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“…Previous investigators have already reported a similar decreased F/S ratio in the blood of premature infants7 10 12 and from the urinary steroid metabolome of PT or T neonates 11. This potential decrease in 11β-hydroxylase activity is also supported by the modest expression of CYP11B1 transcripts from 22 to 29 GW in human adrenals 33. Finally, despite higher levels of steroid precursors, a marked increase in cortisol and aldosterone blood levels was observed in VPT neonates between the birth and day 3 (figure 5), as also previously reported in healthy or sick PT neonates 7 9 34 35.…”

Section: Discussionsupporting

confidence: 53%

Alterations of adrenal steroidomic profiles in preterm infants at birth

Travers

Boileau

Lombès

et al. 2017

Arch Dis Child Fetal Neonatal Ed

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“…Interestingly, it has been noticed that in mice, mast cell infiltration in adrenals is dependent on strains and gender (more abundant in female), and augments with age [32]. As regards human fetal adrenal development, tryptase expression, which reflects activation of mast cells, raises during the third trimester of gestation, just preceding the appearance of aldosterone synthase expression [33]. This observation suggests that mast cells control differentiation of adrenocortical cells involved in mineralocorticoid production.…”

Section: Regulation Of Adrenal Mast Cellsmentioning

confidence: 99%

Role of Mast Cells in the Control of Aldosterone Secretion

et al. 2020

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Mast cells are immune cells present in adrenals from various species. Proliferation and activation of adrenal mast cells seem to be influenced by environment, since they increase during summer and in response to sodium restriction in frogs and mouse, respectively. Although the physiological factors regulating adrenal mast cell activity have not been identified, they might involve neurotransmitters and the renin-angiotensin system. Some data indicate that adrenal mast cells stimulate proliferation of steroidogenic cells in the zona glomerulosa and activate the mineralocorticoid production. In human, mast cell degranulation stimulates aldosterone synthesis through the release of serotonin (5-HT) and activation of 5-HT4 receptors. Increase in mast cell population and upregulation of the 5-HT signaling pathway occur in aldosterone-producing adenomas. In particular, aldosterone-producing adenoma cells overexpress 5-HT4 receptors and are hyper-responsive to 5-HT4 receptor agonists. These data suggest that the intra-adrenal serotonergic regulatory system represents a potential target for development of both adrenal imaging methods to evaluate the lateralization of aldosterone production, and pharmacological treatments of primary aldosteronism.

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Temporal and spatial distribution of mast cells and steroidogenic enzymes in the human fetal adrenal

Cited by 25 publications

References 47 publications

The human fetal adrenal produces cortisol but no detectable aldosterone throughout the second trimester

The human fetal adrenal produces cortisol but no detectable aldosterone throughout the second trimester

Alterations of adrenal steroidomic profiles in preterm infants at birth

Role of Mast Cells in the Control of Aldosterone Secretion

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