PMID- 8612506
OWN - NLM
STAT- MEDLINE
DCOM- 19960605
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 137
IP  - 5
DP  - 1996 May
TI  - Suppression of endogenous corticosterone levels in vivo increases the 
      steroidogenic capacity of purified rat Leydig cells in vitro.
PG  - 1714-8
AB  - In vitro studies have shown that corticosterone (B) directly inhibits 
      testosterone (T) production by purified Leydig cells but does so only at high 
      concentrations. 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) in Leydig 
      cells oxidatively inactivates B, lowering its effective concentration, thus 
      protecting against the suppressive effect of glucocorticoid on T production. The 
      aim of the present study was to assess the significance of B at physiological 
      levels in modulating T production and 11 beta-HSd activity in Leydig cells. To 
      determine the effects of endogenous B on Leydig cell steroidogenesis, male rats 
      (200-250 g body wt) were adrenalectomized (ADX), while control rats were 
      subjected to sham surgery (SHAM). Seven days after surgery: T and LH were 
      measured in serum; T production was measured in aliquots of spent culture media 
      from 3-h incubations of purified Leydig cells; 11 beta-HSD activity and messenger 
      RNA was measured in purified Leydig cells. ADX rats had elevated serum T (P < 
      0.05) in contrast to SHAM control or ADX rats that received B replacement (1 
      mg/100 g body wt per day, i.p., on the final 3 days). Serum LH levels were 
      uninfluenced by ADX, with or without B replacement (SHAM), 0.45 +/- 0.16 ng/ml; 
      ADX, 0.35 +/- 0.13 ng/ml; ADX + B, 0.61 +/- 0.09 ng/ml, NS, P > 0.05). This 
      indicated that the alteration of T production was induced by a mechanism that is 
      independent of LH. ADX nearly doubled LH-stimulated T production by purified 
      Leydig cells, from 106.3 +/- 9.3 (SHAM) to 183.2 +/- 16.7 (ADX) ng/10(6) cells.3 
      h (mean +/- SEM for three replications of the experiment, P < or = 0.02). T 
      production by Leydig cells from the ADX + B treatment group was suppressed to 53% 
      of SHAM values, indicating that B inhibits T production after ADX. The oxidative 
      activity of 11 beta-HSD in Leydig cells exceeded its reductive activity, and both 
      activities declined after ADX. The decline in 11 beta-HSD activities after ADX 
      was prevented by B replacement. Similarly, the steady state levels of 11 beta-HSD 
      messenger RNA declined in Leydig cells after ADX, and this decline was prevented 
      by B replacement. We conclude that physiological levels of B exert a tonic, 
      negative control directly on Leydig cell steroidogenesis and also induce 
      intracellular 11 beta-HSD activity, thereby protecting against B-mediated 
      inhibition of T production. By modulating the level of active glucocorticoid in 
      Leydig cells, 11 beta-HSD is thus a significant determinant of their 
      steroidogenic capacity.
FAU - Gao, H B
AU  - Gao HB
AD  - Center for Biomedical Research, Population Council, New York, New York 10021, 
      USA.
FAU - Shan, L X
AU  - Shan LX
FAU - Monder, C
AU  - Monder C
FAU - Hardy, M P
AU  - Hardy MP
LA  - eng
GR  - R29 HD-32588-01/HD/NICHD 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  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (RNA, Messenger)
RN  - 3XMK78S47O (Testosterone)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Adrenalectomy
MH  - Animals
MH  - Base Sequence
MH  - Corticosterone/*blood/pharmacology
MH  - Hydroxysteroid Dehydrogenases/genetics/metabolism
MH  - Leydig Cells/drug effects/*metabolism
MH  - Luteinizing Hormone/blood
MH  - Male
MH  - Molecular Sequence Data
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Testosterone/*biosynthesis/blood
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
AID - 10.1210/endo.137.5.8612506 [doi]
PST - ppublish
SO  - Endocrinology. 1996 May;137(5):1714-8. doi: 10.1210/endo.137.5.8612506.