THE HUMAN TISSUE PROTEOMES

Full section samples of adrenal gland



The Tissue atlas is based on immunohistochemical staining of tissue microarrays from 44 different normal tissue types. In addition to the standard setup, extended tissue profiling is performed for selected proteins, to give a more complete overview on where the protein is expressed. Extended tissue samples include mouse brain, human lactating breast, eye and additional samples of adrenal gland, skin and brain. For adrenal gland, full section samples were used.

The full list of proteins analyzed in full section adrenal gland is found in Table 1.


Background


The adrenal glands are paired endocrine glands attached on top of each kidney. Each gland consists of an outer cortex and an inner medulla, each with a different type of endocrine tissue; the cortex consists of glandular tissue and the medulla of nervous tissue. The cortex is divided into three layers, namely zona glomerulosa, zona fasciculata and zona reticularis.


Adrenal cortex


The adrenal cortex produces and secretes three types of cholesterol based steroid hormones; mineralocorticoids, glucocorticoids and androgens. The outermost layer of the adrenal cortex is the zona glomerulosa, which produces mineralocorticoids such as aldosterone. Aldosterone is important for the regulation of blood pressure and electrolyte balance. Glucocorticoids, such as cortisol, are produced in the middle layer; zona fasciculata. Functions of glucocorticoids include carbohydrate, protein and lipid metabolism and immune system suppression. For example, cortisol raises blood glucose levels and cellular synthesis of glucose. The innermost layer of the cortex, zona reticularis, produces androgens (sex hormones) and small amounts of glucocorticoids. An example of a protein expressed in the adrenal cortex is cholesterol side-chain cleavage enzyme, mitochondrial (CYP11A1), which is involved in drug metabolism and synthesis of cholesterol, steroids and other lipids (Figure 1).

Figure 1. Immunohistochemical staining of full section adrenal gland using an antibody toward CYP11A1 shows strong cytoplasmic positivity in adrenal cortex.


Adrenal medulla


The adrenal medulla produces the catecholamines adrenaline and noradrenaline, which increase heart rate and respiration, and lead to vasodilation and glucose production in the liver. The secretion of adrenaline and noradrenaline is regulated by the autonomous nervous system. An example of a protein expressed in the adrenal medulla is dopamine beta-hydroxylase (DBH), which converts dopamine to norepinephrine (Figure 2).

Figure 2. Immunohistochemical staining of full section adrenal gland using an antibody toward DBH shows strong cytoplasmic positivity in adrenal medulla.



Table 1. The following 25 genes have been analyzed using full section adrenal gland tissue samples.

Gene

Gene description

Staining pattern

AKR1B1 Aldo-keto reductase family 1, member B1 (aldose reductase) Adrenal cortex showed strong nuclear and cytoplasmic positivity. Cells in adrenal medulla were negative.
ARHGAP36 Rho GTPase activating protein 36 Strong cytoplasmic staining was observed in adrenal medulla. Adrenal cortex was negative.
CHGB Chromogranin B Strong cytoplasmic positivity was observed in medullary cells. A subset of cells in adrenal cortex showed moderate staining. Remaining cortical cells were mainly negative.
CYP11A1 Cytochrome P450, family 11, subfamily A, polypeptide 1 Strong cytoplasmic positivity was displayed in adrenal cortex.
CYP11B1 Cytochrome P450, family 11, subfamily B, polypeptide 1 Strong cytoplasmic positivity was displayed in adrenal cortex.
CYP11B2 Cytochrome P450, family 11, subfamily B, polypeptide 2 Strong cytoplasmic positivity was displayed in adrenal cortex.
CYP17A1 Cytochrome P450, family 17, subfamily A, polypeptide 1 Strong cytoplasmic positvity was observed in adrenal cortex. Adrenal medulla was negative.
CYP21A2 Cytochrome P450, family 21, subfamily A, polypeptide 2 Strong cytoplasmic positivity was observed in adrenal cortex. Adrenal medulla was negative.
DBH Dopamine beta-hydroxylase (dopamine beta-monooxygenase) Strong cytoplasmic positivity was observed in adrenal medulla.
ELAVL4 ELAV like neuron-specific RNA binding protein 4 Strong nuclear positivity was observed in adrenal medulla. Adrenal cortex was negative.
ELOVL5 ELOVL fatty acid elongase 5 Strong granular cytoplasmic positivity was observed in adrenal cortex. Adrenal medulla showed moderate nuclear staining.
FDX1 Ferredoxin 1 Strong cytoplasmic positivity was displayed in adrenal cortical cells.
HSD3B1 Hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 Strong cytoplasmic positivity was observed in zona glomerulosa and fasciculata. Cells in zona reticularis and medullary cells were negative.
HSD3B2 Hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 Strong cytoplasmic positivity was observed in zona glomerulosa and fasciculata. Cells in zona reticularis and medullary cells were negative.
MGARP Mitochondria-localized glutamic acid-rich protein Strong cytoplasmic positivity with a granular pattern was observed in adrenal cotex. Adrenal medulla was negative.
NOV Nephroblastoma overexpressed Strong cytoplasmic positivity was displayed in cells in zona glomerulosa and fractions of cells in zona fasciculata. Cells in zona reticularis and medullary cells were negative.
PENK Proenkephalin Strong cytoplasmic positivity was displayed in selected cells in adrenal medulla. Adrenal cortex was mainly negative.
PNMT Phenylethanolamine N-methyltransferase Strong cytoplasmic positivity was observed in adrenal medulla. Adrenal cortex was negative.
PTPRN Protein tyrosine phosphatase, receptor type, N Strong cytoplasmic positivity was displayed in adrenal medulla.
RGN Regucalcin Strong cytoplasmic, nuclear and membranous positivity was observed in adrenal cortex.
RIMS2 Regulating synaptic membrane exocytosis 2 Strong granulated cytoplasmic positivity was observed in adrenal cortex. Adrenal medulla was negative.
SLC18A1 Solute carrier family 18 (vesicular monoamine transporter), member 1 Stronf cytolasmic postivity was observed in adrenal medulla. Adrenal cortex was negative.
STAR Steroidogenic acute regulatory protein Strong cytoplasmic positivity was observed in adrenal cortex.
TH Tyrosine hydroxylase Strong cytoplasmic positivity was displyed in adrenal medulla. Cells in adrenal cortex were negative.
VGF VGF nerve growth factor inducible Strong cytoplasmic postivity was observed in adrenal medulla. Adrenal cortex was mainly negative.


Relevant links and publications


Uhlén M et al, 2015. Tissue-based map of the human proteome. Science
PubMed: 25613900 DOI: 10.1126/science.1260419

Yu NY et al, 2015. Complementing tissue characterization by integrating transcriptome profiling from the Human Protein Atlas and from the FANTOM5 consortium. Nucleic Acids Res.
PubMed: 26117540 DOI: 10.1093/nar/gkv608

Fagerberg L et al, 2014. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics.
PubMed: 24309898 DOI: 10.1074/mcp.M113.035600