PMID- 19036885
OWN - NLM
STAT- MEDLINE
DCOM- 20090414
LR  - 20211020
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 150
IP  - 4
DP  - 2009 Apr
TI  - The developmental increase in adrenocortical 17,20-lyase activity (biochemical 
      adrenarche) is driven primarily by increasing cytochrome b5 in neonatal rhesus 
      macaques.
PG  - 1748-56
LID - 10.1210/en.2008-1303 [doi]
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 
      17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450c17), cytochrome b5 (b5), 
      and 3beta-hydroxysteroid dehydrogenase (3betaHSD), 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 3betaHSD 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. Cotransfection 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 3betaHSD, as 
      suggested from human studies. The rhesus macaque is a relevant and accessible 
      model for human ZR development and adrenal function.
FAU - Nguyen, Ann D
AU  - Nguyen AD
AD  - Department of Population Health and Reproduction, School of Veterinary Medicine, 
      University of California, Davis, California 95616, USA.
FAU - Corbin, C Jo
AU  - Corbin CJ
FAU - Pattison, J Christina
AU  - Pattison JC
FAU - Bird, Ian M
AU  - Bird IM
FAU - Conley, Alan J
AU  - Conley AJ
LA  - eng
GR  - T32 HD041921/HD/NICHD NIH HHS/United States
GR  - T32HD 41921/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20081126
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 9035-39-6 (Cytochromes b5)
RN  - EC 1.1.- (3-Hydroxysteroid Dehydrogenases)
RN  - EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase)
SB  - IM
MH  - 3-Hydroxysteroid Dehydrogenases/metabolism/physiology
MH  - Animals
MH  - Animals, Newborn
MH  - Blotting, Western
MH  - Cell Line
MH  - Chromatography, Thin Layer
MH  - Cytochromes b5/genetics/*metabolism/physiology
MH  - Gene Expression Regulation, Developmental/genetics/physiology
MH  - Humans
MH  - Macaca mulatta/*metabolism
MH  - Microsomes/metabolism
MH  - Steroid 17-alpha-Hydroxylase/*metabolism
PMC - PMC2732332
EDAT- 2008/11/28 09:00
MHDA- 2009/04/15 09:00
PMCR- 2010/04/01
CRDT- 2008/11/28 09:00
PHST- 2008/11/28 09:00 [pubmed]
PHST- 2009/04/15 09:00 [medline]
PHST- 2008/11/28 09:00 [entrez]
PHST- 2010/04/01 00:00 [pmc-release]
AID - en.2008-1303 [pii]
AID - 4642 [pii]
AID - 10.1210/en.2008-1303 [doi]
PST - ppublish
SO  - Endocrinology. 2009 Apr;150(4):1748-56. doi: 10.1210/en.2008-1303. Epub 2008 Nov 
      26.