Expression of steroidogenic enzymes in the bovine placenta and fetal adrenal glands throughout gestation.

The onset of steroidogenesis in human fetal adrenal glands (HFA) during the first trimester is poorly investigated. An unresolved question is the capacity of the HFA to produce potent androgen DHT via conventional and/or the backdoor pathway(s) at the end of first trimester, when androgen-responsive organs are developed. Our aim was to explore steroidogenesis and the expression of steroidogenic enzymes and transcription factors in HFA at gestational weeks (GW) 9–12 with focus on their androgenic potential. Steroids in the HFA were analyzed by gas chromatography/mass spectrometry. The expression of steroidogenic enzymes and transcription factors in the HFA at GW9–12 was investigated by qPCR, automated Western blotting and immunohistochemistry. We demonstrated that during GW9–12 HFA produced steroids of the ∆5, ∆4 and the backdoor pathways of the biosynthesis of DHT, though the latter was limited to production of 17α-OH-dihydroprogesterone, androsterone and androstanedione without further conversion to DHT. The only androgens identified in the HFA were testosterone and androsterone, a precursor in the biosynthesis of DHT. We also observed higher levels of CYP17A1 but low expression of 3βHSD2 at GW11–12 in the HFA. Elevated levels of CYP17A1 were associated with an increased expression of SF-1 and GATA-6. Altogether, our data demonstrate that of those steroids analyzed, the only potent androgen directly produced by the HFA at GW9–12 was testosterone. The onset of steroidogenesis in the HFA is a complex process that is regulated by the coordinated action of related transcription factors.

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Immunolocalization of Steroidogenic Enzymes in Equine Fetal Adrenal Glands During Mid-Late Gestation

Journal of Reproduction and Development ◽

10.1262/jrd.18159 ◽

2007 ◽

Vol 53 (5) ◽

pp. 1093-1098 ◽

Cited By ~ 4

Author(s):

Qiang WENG ◽

Yumiko TANAKA ◽

Hiroyuki TANIYAMA ◽

Nobuo TSUNODA ◽

Yasuo NAMBO ◽

...

Keyword(s):

Adrenal Glands ◽

Late Gestation ◽

Steroidogenic Enzymes

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Hypocretin/orexin increases the expression of steroidogenic enzymes in human adrenocortical NCI H295R cells

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.91034.2008 ◽

2009 ◽

Vol 297 (5) ◽

pp. R1601-R1609 ◽

Cited By ~ 28

Author(s):

Jan Wenzel ◽

Nicole Grabinski ◽

Cordula A. Knopp ◽

Andreas Dendorfer ◽

Manjunath Ramanjaneya ◽

...

Keyword(s):

Adrenal Glands ◽

Synthesis Rate ◽

Receptor Subtypes ◽

Mrna Levels ◽

Steroidogenic Enzymes ◽

Orexin A ◽

Orexin Receptors ◽

Adrenal Steroidogenesis ◽

Intracellular Ca ◽

H295r Cells

Hypocretins/orexins act through two receptor subtypes: OX1 and OX2. Outside the brain, orexin receptors are expressed in adrenal glands, where orexins stimulate the release of glucocorticoids. To further address the regulation of steroidogenesis, we analyzed the effect of orexins on the expression of steroidogenic enzymes in human adrenocortical National Cancer Institute (NCI) H295R cells by qPCR. In NCI H295R cells, OX2 receptors were highly expressed, as they were in human adrenal glands. After treatment of NCI H295R cells with orexin A for 12–24 h, the cortisol synthesis rate was significantly increased, whereas 30 min of treatment showed no effect. While CYP11B1 and CYP11B2 mRNA levels were increased already at earlier time points, the expression of HSD3B2 and CYP21 mRNA was significantly up-regulated after treatment with orexin A for 12 h. Likewise, orexin B increased CYP21 and HSD3B2 mRNA levels showing, however, a lower potency compared with orexin A. The mRNA levels of CYP11A and CYP17 were unaffected by orexin A. OX2 receptor mRNA levels were down-regulated after 12 and 24 h of orexin A treatment. Orexin A increased intracellular Ca2+ but not cAMP concentrations in NCI H295R cells. Furthermore, inhibition of PKC and MAPK kinase/ERK kinase (MEK1/2) prevented the increase of HSD3B2 expression by orexin A. Accordingly, orexin A treatment of NCI H295R cells markedly enhanced ERK1/2 phosphorylation that was prevented by PKC and, in part, PKA inhibition. In conclusion, orexins may influence adrenal steroidogenesis by differential regulation of the expression of steroidogenic enzymes involving Ca2+, as well as PKC-ERK1/2 signaling.

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Effect of particulate antigenic stimulation or in vivo administration of interleukin-6 on the level of steroidogenic enzymes in adrenal glands and lymphoid tissues of mice with parallel alteration in endogenous inflammatory cytokine level

Cellular Immunology ◽

10.1016/j.cellimm.2009.10.005 ◽

2010 ◽

Vol 261 (1) ◽

pp. 23-28 ◽

Cited By ~ 3

Author(s):

Rupanjan Mukhopadhyay ◽

Manoj K. Mishra ◽

Anirban Basu ◽

Biswadev Bishayi

Keyword(s):

Interleukin 6 ◽

Inflammatory Cytokine ◽

Adrenal Glands ◽

Cytokine Level ◽

Antigenic Stimulation ◽

Lymphoid Tissues ◽

Steroidogenic Enzymes ◽

In Vivo Administration

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Localization of cytochrome P450 cholesterol side-chain cleavage, cytochrome P450 17 alpha-hydroxylase/17, 20-lyase, and 3 beta- hydroxysteroid dehydrogenase isomerase steroidogenic enzymes in human and rhesus monkey fetal adrenal glands: reappraisal of functional zonation

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.77.5.1184 ◽

1993 ◽

Vol 77 (5) ◽

pp. 1184-1189 ◽

Cited By ~ 32

Author(s):

S. Mesiano

Keyword(s):

Cytochrome P450 ◽

Rhesus Monkey ◽

Adrenal Glands ◽

Hydroxysteroid Dehydrogenase ◽

Side Chain ◽

Steroidogenic Enzymes ◽

Side Chain Cleavage ◽

Chain Cleavage

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Localization of cytochrome P450 cholesterol side-chain cleavage, cytochrome P450 17 alpha-hydroxylase/17, 20-lyase, and 3 beta-hydroxysteroid dehydrogenase isomerase steroidogenic enzymes in human and rhesus monkey fetal adrenal glands: reappraisal of functional zonation.

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.77.5.8077311 ◽

1993 ◽

Vol 77 (5) ◽

pp. 1184-1189

Author(s):

S Mesiano ◽

C L Coulter ◽

R B Jaffe

Keyword(s):

Cytochrome P450 ◽

Rhesus Monkey ◽

Adrenal Glands ◽

Hydroxysteroid Dehydrogenase ◽

Side Chain ◽

Steroidogenic Enzymes ◽

Side Chain Cleavage ◽

Chain Cleavage

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Glucocorticoid production in lymphoid organs: Acute effects of lipopolysaccharide in neonatal and adult mice

Endocrinology ◽

10.1210/endocr/bqab244 ◽

2021 ◽

Author(s):

Melody Salehzadeh ◽

Jordan E Hamden ◽

Michael X Li ◽

Hitasha Bajaj ◽

Ruolan S Wu ◽

...

Keyword(s):

Hpa Axis ◽

Adrenal Glands ◽

Lymphoid Organs ◽

Acute Effects ◽

Steroidogenic Enzymes ◽

Steroidogenic Enzyme ◽

Adult Mice ◽

Liquid Chromatography Tandem Mass ◽

Glucocorticoid Production ◽

Local Expression

Abstract Glucocorticoids (GCs) are critical modulators of the immune system. The hypothalamic-pituitary-adrenal (HPA) axis regulates circulating GC levels and is stimulated by endotoxins. Lymphoid organs also produce GCs; however, it is not known how lymphoid GC levels are regulated in response to endotoxins. We assessed whether an acute challenge of lipopolysaccharide (LPS) increases lymphoid levels of GCs, steroidogenic enzymes expression, and components of the HPA axis (e.g., CRH) expression. We administered LPS (50µg/kg i.p.) or vehicle control to male and female C57BL/6J neonatal (post-natal day (PND) 5) and adult (PND90) mice and collected blood, bone marrow, thymus, and spleen 4 hr later. We measured progesterone, 11-deoxycorticosterone (DOC), corticosterone, and 11-dehydrocorticosterone (DHC) via liquid chromatography tandem mass spectrometry (LC-MS/MS). We measured gene expression of key steroidogenic enzymes (Cyp11b1, Hsd11b1, and Hsd11b2) and HPA axis components (Crh, Crhr1, Pomc, and Mc2r) via qPCR. At PND5, LPS induced greater increases in steroid levels in lymphoid organs than in blood. In contrast, at PND90, LPS induced greater increases in steroid levels in blood than in lymphoid organs. Steroidogenic enzyme transcripts were present in all lymphoid organs, and LPS altered steroidogenic enzyme expression predominately in the spleen. Lastly, we detected transcripts of key HPA axis components in all lymphoid organs, and there was an effect of LPS in the spleen. Taken together, these data suggest that LPS regulates GC production by lymphoid organs, similar to its effects on the adrenal glands, and the effects of LPS might be mediated by local expression of CRH and ACTH.

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Fusion and Fission Processes in Exocytosis: Possible Roles for Synexin and Osmotic Lysis in the Two Events

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002634 ◽

1980 ◽

Vol 38 ◽

pp. 594-597

Author(s):

H.B. Pollard ◽

C.E. Creutz ◽

C.J. Pazoles ◽

J.H. Scott

Keyword(s):

Small Molecules ◽

Chromaffin Cells ◽

Adrenal Glands ◽

General Concept ◽

Extracellular Calcium ◽

Large Protein ◽

Granule Membrane ◽

Osmotic Lysis ◽

Per Se ◽

Chemical Evidence

Exocytosis is a general concept describing secretion of enzymes, hormones and transmitters that are otherwise sequestered in intracellular granules. Chemical evidence for this concept was first gathered from studies on chromaffin cells in perfused adrenal glands, in which it was found that granule contents, including both large protein and small molecules such as adrenaline and ATP, were released together while the granule membrane was retained in the cell. A number of exhaustive reviews of this early work have been published and are summarized in Reference 1. The critical experiments demonstrating the importance of extracellular calcium for exocytosis per se were also first performed in this system (2,3), further indicating the substantial service given by chromaffin cells to those interested in secretory phenomena over the years.

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