Abstract
Adrenarche is thought to be experienced only by humans and some Old World primates despite observed regression of an adrenal fetal zone and establishment of a functional zona reticularis (ZR) in other species like rhesus macaques. Adrenal differentiation remains poorly defined biochemically in nonhuman primates. The present studies defined ZR development in the neonatal rhesus by examining androgen synthetic capacity and factors affecting it in rhesus and marmoset adrenals. Western immunoblots examined expression of 17α-hydroxylase/17, 20-lyase cytochrome P450 (P450c17), cytochrome b5 (b5), and 3β-hydroxysteroid dehydrogenase (3βHSD), among other key enzymes. 17, 20-lyase activity was quantified in adrenal microsomes, as was the contribution of b5 to 17, 20-lyase activity in microsomes and cell transfection experiments with rhesus and marmoset P450c17. Expression of b5 increased from birth to 3 months, and was positively correlated with age and 17, 20-lyase activity in the rhesus. Recombinant b5 addition stimulated 17, 20-lyase activity to an extent inversely proportional to endogenous levels in adrenal microsomes. Although 3βHSD expression also increased with age, P450c17, 21-hydroxylase cytochrome P450, and the redox partner, reduced nicotinamide adenine dinucleotide phosphate-cytochrome P450 oxidoreductase, did not; nor did recombinant cytochrome P450 oxidoreductase augment 17, 20-lyase activity. Co-transfection with b5 induced a dose-dependent increase in dehydroepiandrosterone synthesis by both nonhuman primate P450c17 enzymes. We conclude that the increase in 17, 20-lyase activity characteristic of an adrenarche in rhesus macaques is driven primarily by increased b5 expression, without the need for a decrease in 3βHSD, as suggested from human studies. The rhesus macaque is a relevant and accessible model for human ZR development and adrenal function.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1748-1756 |
| Number of pages | 9 |
| Journal | Endocrinology |
| Volume | 150 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2009 |
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- Endocrinology
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The developmental increase in adrenocortical 17, 20-lyase activity (biochemical adrenarche) is driven primarily by increasing cytochrome b5 in neonatal rhesus macaques. / Nguyen, Ann D.; Corbin, C. Jo; Pattison, J. Christina; Bird, Ian M.; Conley, Alan J.
In: Endocrinology, Vol. 150, No. 4, 04.2009, p. 1748-1756.Research output: Contribution to journal › Article
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TY - JOUR
T1 - The developmental increase in adrenocortical 17, 20-lyase activity (biochemical adrenarche) is driven primarily by increasing cytochrome b5 in neonatal rhesus macaques
AU - Nguyen, Ann D.
AU - Corbin, C. Jo
AU - Pattison, J. Christina
AU - Bird, Ian M.
AU - Conley, Alan J
PY - 2009/4
Y1 - 2009/4
N2 - Adrenarche is thought to be experienced only by humans and some Old World primates despite observed regression of an adrenal fetal zone and establishment of a functional zona reticularis (ZR) in other species like rhesus macaques. Adrenal differentiation remains poorly defined biochemically in nonhuman primates. The present studies defined ZR development in the neonatal rhesus by examining androgen synthetic capacity and factors affecting it in rhesus and marmoset adrenals. Western immunoblots examined expression of 17α-hydroxylase/17, 20-lyase cytochrome P450 (P450c17), cytochrome b5 (b5), and 3β-hydroxysteroid dehydrogenase (3βHSD), among other key enzymes. 17, 20-lyase activity was quantified in adrenal microsomes, as was the contribution of b5 to 17, 20-lyase activity in microsomes and cell transfection experiments with rhesus and marmoset P450c17. Expression of b5 increased from birth to 3 months, and was positively correlated with age and 17, 20-lyase activity in the rhesus. Recombinant b5 addition stimulated 17, 20-lyase activity to an extent inversely proportional to endogenous levels in adrenal microsomes. Although 3βHSD expression also increased with age, P450c17, 21-hydroxylase cytochrome P450, and the redox partner, reduced nicotinamide adenine dinucleotide phosphate-cytochrome P450 oxidoreductase, did not; nor did recombinant cytochrome P450 oxidoreductase augment 17, 20-lyase activity. Co-transfection with b5 induced a dose-dependent increase in dehydroepiandrosterone synthesis by both nonhuman primate P450c17 enzymes. We conclude that the increase in 17, 20-lyase activity characteristic of an adrenarche in rhesus macaques is driven primarily by increased b5 expression, without the need for a decrease in 3βHSD, as suggested from human studies. The rhesus macaque is a relevant and accessible model for human ZR development and adrenal function.
AB - Adrenarche is thought to be experienced only by humans and some Old World primates despite observed regression of an adrenal fetal zone and establishment of a functional zona reticularis (ZR) in other species like rhesus macaques. Adrenal differentiation remains poorly defined biochemically in nonhuman primates. The present studies defined ZR development in the neonatal rhesus by examining androgen synthetic capacity and factors affecting it in rhesus and marmoset adrenals. Western immunoblots examined expression of 17α-hydroxylase/17, 20-lyase cytochrome P450 (P450c17), cytochrome b5 (b5), and 3β-hydroxysteroid dehydrogenase (3βHSD), among other key enzymes. 17, 20-lyase activity was quantified in adrenal microsomes, as was the contribution of b5 to 17, 20-lyase activity in microsomes and cell transfection experiments with rhesus and marmoset P450c17. Expression of b5 increased from birth to 3 months, and was positively correlated with age and 17, 20-lyase activity in the rhesus. Recombinant b5 addition stimulated 17, 20-lyase activity to an extent inversely proportional to endogenous levels in adrenal microsomes. Although 3βHSD expression also increased with age, P450c17, 21-hydroxylase cytochrome P450, and the redox partner, reduced nicotinamide adenine dinucleotide phosphate-cytochrome P450 oxidoreductase, did not; nor did recombinant cytochrome P450 oxidoreductase augment 17, 20-lyase activity. Co-transfection with b5 induced a dose-dependent increase in dehydroepiandrosterone synthesis by both nonhuman primate P450c17 enzymes. We conclude that the increase in 17, 20-lyase activity characteristic of an adrenarche in rhesus macaques is driven primarily by increased b5 expression, without the need for a decrease in 3βHSD, as suggested from human studies. The rhesus macaque is a relevant and accessible model for human ZR development and adrenal function.
UR - http://www.scopus.com/inward/record.url?scp=63849311167&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=63849311167&partnerID=8YFLogxK
U2 - 10.1210/en.2008-1303
DO - 10.1210/en.2008-1303
M3 - Article
C2 - 19036885
AN - SCOPUS:63849311167
VL - 150
SP - 1748
EP - 1756
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 4
ER -