Quantitative assessment of CYP11B1 and CYP11B2 expression in aldosterone-producing adenomas

Abstract

Background: The presence and pathophysiological role of CYP11B1 (11b-hydroxylase) gene in the zona glomerulosa of human adrenal cortex is still controversial. Methods: In order to specifically quantify CYP11B1, CYP11B2 (aldosterone synthase) and CYP17(17a-hydroxylase) mRNA levels, we developed a real-time RT-PCR assay and examined the expression in a series of adrenal tissues, including six normal adrenals from patients adrenalectomized for renal cancer and twelve aldosterone-producing adenomas (APA) from patients with primary aldosteronism. Results: CYP11B1 mRNA levels were clearly detected in normal adrenals, which comprised both zona glomerulosa and fasciculata/reticularis cells, but were also measured at a lower range ðP , 0:05Þ in APA. The levels of CYP11B2 mRNA were lower ðP , 0:005Þ in normal adrenals than in APA. CYP17 mRNAlevels were similar in normal adrenals and in APA. In patients with APA, CYP11B2 and CYP11B1 mRNA levels were not correlated either with basal aldosterone or with the change from basal aldosterone in response to posture or to dexamethasone. No correlation between CYP11B1 mRNA or CYP11B2 mRNA and the percentage of zona fasciculata-like cells was observed in APA. Conclusions: Real-time RT-PCR can be reliably used to quantify CYP11B1 and CYP11B2 mRNA levels in adrenal tissues. Expression of CYP11B1 in hyperfunctioning zona glomerulosa suggests an additional formation of corticosterone via 11b-hydroxylase, providing further substrate for aldosterone biosynthesis. CYP11B1 and CYP11B2 mRNA levels in APA are not related to the in vivo secretory activity of glomerulosa cells, where post-transcriptional factors might ultimately regulate aldosterone production.

Integrating Genetics and Genomics in Primary Aldosteronism

“…32 Most unexpectedly, however, different authors found subsets of tumors with highly heterogeneous expression of CYP11B2 either increased, unchanged, or decreased compared with control adrenal tissue. 34,36 A very recent transcriptome study further demonstrated the tumor heterogeneity of CYP11B2 expression and the correlation of high versus low CYP17A1 expression in APA with morphological features, that is, adenomas composed of zona fasciculata-like cells versus tumors composed of ZG-like cells, respectively.…”

“…Using various techniques, several studies have thus reported increased expression of CYP11B2 in APA compared with normal adrenals or peritumoral adjacent cortex [31][32][33][34][35][36] (throughout this review, "adjacent cortex" refers to the entire cortex of an adrenal gland harboring an APA). In addition to CYP11B2, expression of CYP21A2 (coding for steroid 21-hydroxylase, responsible for the conversion of progesterone into 11-deoxycorticosterone) has been found to be consistently increased in APA, 37,38 whereas mRNA levels of CYP11B1 were decreased, 32,38 and there were no changes in CYP11A1 expression. 36 Remarkably enough, these studies also revealed a relative heterogeneity in terms of gene expression.…”

Cortisol Synthesis in Epidermis Is Induced by IL-1 and Tissue Injury

“…1D). Surprisingly, the level of enzyme detected in skin was comparable to the adrenal gland (51). Protein extracts from lymphocytes, which do not express CYP11B1 (52), were used as a negative control, and no signal was detected.…”

Tumores testiculares bilaterais por hiperplasia congênita de restos adrenais

“…Quando restos adrenais estão presentes na rede testicular, pequenas elevações ou elevações intermitentes do ACTH e da angiotensina II (AII) podem induzir a proliferação dessas células no testículo. Sugere-se que a AII seja um importante fator na estimulação do crescimento adrenal (8,9). Além disso, o controle hormonal inadequado, com elevações mais pronunciadas do ACTH, poderia acelerar esse processo.…”