PMID- 9768686
OWN - NLM
STAT- MEDLINE
DCOM- 19981105
LR  - 20161124
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 83
IP  - 10
DP  - 1998 Oct
TI  - Adrenarche results from development of a 3beta-hydroxysteroid 
      dehydrogenase-deficient adrenal reticularis.
PG  - 3695-701
AB  - Adrenarche is the increased adrenal production of dehydroepiandrosterone (DHEA) 
      and dehydroepiandrosterone sulfate (DHEAS) that occurs during the prepubertal 
      period. To date, the exact mechanism initiating adrenarche is unknown, although 
      many factors have been postulated. In the present study, we examined the 
      hypothesis that alterations in intra-adrenal expression of 3beta-hydroxysteroid 
      dehydrogenase (3betaHSD) or 21-hydroxylase (CYP21) within the inner reticularis 
      zone leads to the increased production of 19-carbon (C19) steroids. After 
      conversion of cholesterol to pregnenolone, 17alpha-hydroxylase/17,20-lyase 
      (CYP17) can metabolize pregnenolone through to DHEA. The enzyme 3betaHSD competes 
      for substrate with CYP17 and effectively removes steroid precursor from the 
      pathway leading to DHEA. On the other hand, deficiency in CYP21 expression is 
      known to cause excessive production of adrenal C19 steroids, suggesting that 
      CYP21 could play a role in adrenarche. Thus, a decrease in 3betaHSD or CYP21 
      expression would allow substrate to flow toward the synthesis of DHEA. To 
      determine whether adrenarche results from a decreased expression of 3betaHSD or 
      CYP21 in the reticularis, immunohistochemical localization of 3betaHSD and CYP21 
      was performed, and staining intensities compared using adrenal glands from 
      children ages 4 months to 4 yr (n = 12), ages 5-7 yr (n = 9), ages 8-13 yr (n = 
      9), and adults ages 25-56 yr (n = 8). There were no differences in the zonal 
      expression of CYP21. No difference in 3betaHSD staining was observed between the 
      glomerulosa and fasciculata from any age group. However, children age 8 yr and 
      older show a significant decrease in 3betaHSD expression in reticularis as 
      compared with the fasciculata. No significant difference was noted for 3betaHSD 
      levels between the fasciculata and reticularis for children age 7 yr or younger. 
      The level of 3betaHSD expression in the reticularis continued to decrease in the 
      adult adrenals examined. These findings suggest that as children mature there is 
      a decreased level of 3betaHSD in the adrenal reticularis that may contribute to 
      the increased production of DHEA and DHEAS seen during adrenarche.
FAU - Gell, J S
AU  - Gell JS
AD  - Department of Obstetrics and Gynecology, The University of Texas Southwestern 
      Medical Center, Dallas 75235-9032, USA.
FAU - Carr, B R
AU  - Carr BR
FAU - Sasano, H
AU  - Sasano H
FAU - Atkins, B
AU  - Atkins B
FAU - Margraf, L
AU  - Margraf L
FAU - Mason, J I
AU  - Mason JI
FAU - Rainey, W E
AU  - Rainey WE
LA  - eng
GR  - DK-43140/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - 57B09Q7FJR (Dehydroepiandrosterone Sulfate)
RN  - EC 1.1.- (17-Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.51 (3 (or 17)-beta-hydroxysteroid dehydrogenase)
RN  - EC 1.14.14.16 (Steroid 21-Hydroxylase)
SB  - IM
MH  - 17-Hydroxysteroid Dehydrogenases/*deficiency/metabolism
MH  - Adolescent
MH  - Adrenal Glands/*metabolism
MH  - Adult
MH  - Aging/metabolism
MH  - Child
MH  - Child, Preschool
MH  - Dehydroepiandrosterone/*metabolism
MH  - Dehydroepiandrosterone Sulfate/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Infant
MH  - Middle Aged
MH  - Steroid 21-Hydroxylase/metabolism
EDAT- 1998/10/13 00:00
MHDA- 1998/10/13 00:01
CRDT- 1998/10/13 00:00
PHST- 1998/10/13 00:00 [pubmed]
PHST- 1998/10/13 00:01 [medline]
PHST- 1998/10/13 00:00 [entrez]
AID - 10.1210/jcem.83.10.5070 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1998 Oct;83(10):3695-701. doi: 10.1210/jcem.83.10.5070.