PMID- 8977399
OWN - NLM
STAT- MEDLINE
DCOM- 19970123
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 138
IP  - 1
DP  - 1997 Jan
TI  - Hormonal regulation of oxidative and reductive activities of 11 
      beta-hydroxysteroid dehydrogenase in rat Leydig cells.
PG  - 156-61
AB  - We have proposed that the 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) of 
      Leydig cells protects against glucocorticoid-induced inhibition of testosterone 
      (T) production. However, Leydig cells express type I 11 beta-HSD, which has been 
      shown to be reductive in liver parenchymal cells. Because reduction would have 
      the opposite effect of activating glucocorticoid, the present study was designed 
      to determine: 1) whether Leydig cell 11 beta-HSD is primarily oxidative or 
      reductive; and 2) whether oxidative and reductive activities are separately 
      modified by known regulators of Leydig cell steroidogenic function. Leydig cells 
      and liver parenchymal cells were purified from mature male Sprague-Dawley rats 
      (250 g BW), and 11 beta-HSD oxidative and reductive activities were measured 
      using radiolabeled substrates and TLC of triplicate media samples from 1-h 
      incubations immediately after cell isolation. Enzyme activities also were 
      examined in purified Leydig cells at the end of 3 days of culture in vitro in the 
      presence of LH (10 ng/ml), dexamethasone (DEX, 100 nM), T (50 nM), or epidermal 
      growth factor (EGF, 50 ng/ml). In confirmation of previous reports, the reductive 
      activity of 11 beta-HSD was predominant over oxidation in liver parenchymal 
      cells. In contrast, 11 beta-HSD oxidative activity prevailed over reduction in 
      Leydig cells by a ratio of 2:1. The activities of 11 beta-HSD also were analyzed 
      in Leydig cells that were purified 7 days after endogenous glucocorticoid levels 
      were suppressed by adrenalectomy (ADX). Oxidative activity declined in Leydig 
      cells after ADX (22.53 +/- 1.12 pmol/h.10(6) cells, mean +/- SEM vs. 31.47 +/- 
      1.48 pmol/.10(6) cells in sham-operated controls, P < 0.05), whereas there was no 
      change in reductive activity. This indicated that physiologically active 
      corticosterone is involved in maintaining the predominance of 11 beta-HSD 
      oxidation. When enzyme activities were analyzed in Leydig cells after 3 days of 
      hormonal treatment in vitro, oxidation and reduction were observed to change in 
      opposing directions. Culture of Leydig cells from sham-operated control rats with 
      either LH, T, or EGF resulted in declines in oxidative activity from 33.35 +/- 
      0.77 to 28.24 +/- 1.93, 27.30 +/- 0.96, and 24.13 +/- 1.02 pmol/ h.10(6) cells (x 
      +/- SE), respectively. However, EGF stimulated 11 beta-HSD reductive activity in 
      cultured Leydig cells from both control (from 18.97 +/- 1.10 to 27.16 +/- 0.71 
      pmol/h.10(6) cells and ADX rats (from 16.51 +/- 0.75 to 23.56 +/- 0.84 
      pmol/h.10(6) cells). Among the hormonal treatments, only DEX increased oxidative 
      activity and simultaneously decreased reductive activity in Leydig cells from ADX 
      rats. This increase accentuated the predominance of oxidative activity in Leydig 
      cells, with a ratio of oxidative to reductive activity of 4:1 after DEX 
      treatment, compared with 2:1 in controls that were untreated. We conclude that 11 
      beta-HSD activity in Leydig cells is primarily oxidative. Moreover, oxidation and 
      reduction are regulated separately by hormones.
FAU - Gao, H B
AU  - Gao HB
AD  - Population Council, New York, New York 10021, USA.
FAU - Ge, R S
AU  - Ge RS
FAU - Lakshmi, V
AU  - Lakshmi V
FAU - Marandici, A
AU  - Marandici A
FAU - Hardy, M P
AU  - Hardy MP
LA  - eng
GR  - HD-33000/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Glucocorticoids)
RN  - 0 (RNA, Messenger)
RN  - 3XMK78S47O (Testosterone)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Adrenalectomy
MH  - Animals
MH  - Cells, Cultured
MH  - Epidermal Growth Factor/pharmacology
MH  - Glucocorticoids/pharmacology
MH  - Hydroxysteroid Dehydrogenases/genetics/*metabolism
MH  - Leydig Cells/*enzymology
MH  - Liver/enzymology
MH  - Luteinizing Hormone/pharmacology
MH  - Male
MH  - Oxidation-Reduction
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Testosterone/pharmacology
EDAT- 1997/01/01 00:00
MHDA- 1997/01/01 00:01
CRDT- 1997/01/01 00:00
PHST- 1997/01/01 00:00 [pubmed]
PHST- 1997/01/01 00:01 [medline]
PHST- 1997/01/01 00:00 [entrez]
AID - 10.1210/endo.138.1.4837 [doi]
PST - ppublish
SO  - Endocrinology. 1997 Jan;138(1):156-61. doi: 10.1210/endo.138.1.4837.