PMID- 8793056
OWN - NLM
STAT- MEDLINE
DCOM- 19970311
LR  - 20190512
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 55
IP  - 1
DP  - 1996 Jul
TI  - Altered ovarian sterol carrier protein expression in the pregnant 
      streptozotocin-treated diabetic rat.
PG  - 38-46
AB  - Reproductive dysfunction in the diabetic female rat is associated with impaired 
      folliculogenesis, reduced corpus luteum progesterone output, and spontaneous 
      abortion. The underlying mechanism for reduced steroid production remains 
      unresolved. In this study we examined whether or not diabetes alters levels of 
      P450 side-chain cleavage enzyme (P450scc), 3 beta-hydroxysteroid dehydrogenase (3 
      beta-HSD), or the cholesterol transport proteins, steroidogenic acute regulatory 
      (StAR) protein and sterol carrier protein-2 (SCP2), leading to lower progesterone 
      levels and pregnancy loss. Rats (Day 3 pregnant) received an injection of 
      streptozotocin (STZ, 60 mg/kg; i.v.) to induce a diabetic state; P450scc, 3 
      beta-HSD, and SCP2 were examined by Western and Northern blot analysis in ovarian 
      tissue 12 days after injection of STZ (diabetic rats, n = 12) or vehicle 
      (nondiabetic rats, n = 12). Serum progesterone, triglyceride, and 
      beta-hydroxybutyrate (beta-HBA) levels were also examined. Results indicate that 
      diabetic rats that aborted (diabetic-fetus [Ft], n = 6) had significantly lower 
      progesterone levels (7.04 +/- 2.6 ng/ml; p < 0.004) than nondiabetic animals 
      (108.6 +/- 5.15 ng/ml) and diabetic +Ft animals (74.3 +/- 8.9 ng/ml, n = 6). 
      Western blot analysis of ovarian P450scc and 3 beta-HSD in the nondiabetic rats 
      and the diabetic rats with fetuses indicated no significant difference. In 
      contrast, ovaries from diabetic animals without fetuses had significantly lower 
      SCP2 levels (p < 0.017) compared to controls. Concomitant with the reduction in 
      SCP2, a 58-kDa SCP2-immunoreactive protein, referred to as sterol carrier 
      protein-X (SCPx), increased significantly (p < 0.001). The C-terminal sequence of 
      SCPx is identical to SCP2, while its N-terminal region is homologous with 
      3-oxoacyl coenzyme A thiolase, an enzyme involved in fatty acid metabolism. 
      Increased SCPx expression coincided with increased serum triglyceride and 
      beta-HBA levels, suggesting that the enhanced SCPx level may coincide with an 
      ovarian shift to fatty acid metabolism. When SCPx steady-state mRNA levels were 
      measured using an SCPx-specific riboprobe (280-bp protected fragment) in a 
      ribonuclease protection assay, ovarian SCPx mRNA levels in the diabetic animals 
      were increased 4.2-fold compared to control SCPx mRNA levels. Ovarian StAR mRNA 
      levels were increased slightly in the diabetic animals, and ovarian P450scc and 3 
      beta-HSD mRNA levels were increased 3-fold in the diabetic animals that aborted 
      relative to the nondiabetic animals and the +Ft diabetic animals. Results of this 
      study confirm that SCPx mRNA levels are elevated following diabetes onset and 
      that StAR, P450scc, and 3 beta-HSD mRNA levels do not correspond with the reduced 
      steroid hormone profile associated with diabetes. These results are concordant 
      with the possibility that reduced steroid levels in the diabetic animals reflect 
      a loss of SCP2-mediated cholesterol transport capacity as SCPx/3-oxoacyl coenzyme 
      A thiolase expression is enhanced.
FAU - McLean, M P
AU  - McLean MP
AD  - Department of Obstetrics and Gynecology and Biochemistry and Molecular Biology, 
      University of South Florida, College of Medicine, Tampa 33606, USA.
FAU - Warden, K J
AU  - Warden KJ
FAU - Sandhoff, T W
AU  - Sandhoff TW
FAU - Irby, R B
AU  - Irby RB
FAU - Hales, D B
AU  - Hales DB
LA  - eng
GR  - HD-31644/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  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Blood Glucose)
RN  - 0 (Carrier Proteins)
RN  - 0 (Hydroxybutyrates)
RN  - 0 (Phosphoproteins)
RN  - 0 (Plant Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (steroidogenic acute regulatory protein)
RN  - 0 (sterol carrier proteins)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - EC 1.1.- (3-Hydroxysteroid Dehydrogenases)
RN  - EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme)
RN  - EC 2.3.1.9 (Acetyl-CoA C-Acetyltransferase)
RN  - TZP1275679 (3-Hydroxybutyric Acid)
SB  - IM
MH  - 3-Hydroxybutyric Acid
MH  - 3-Hydroxysteroid Dehydrogenases/genetics/metabolism
MH  - Acetyl-CoA C-Acetyltransferase/*genetics/metabolism
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Carrier Proteins/*genetics/metabolism
MH  - Cholesterol Side-Chain Cleavage Enzyme/genetics/metabolism
MH  - Diabetes Mellitus, Experimental/*metabolism
MH  - Female
MH  - Hydroxybutyrates/blood
MH  - Ovary/*metabolism
MH  - Phosphoproteins/genetics/metabolism
MH  - *Plant Proteins
MH  - Pregnancy
MH  - Pregnancy in Diabetics/*metabolism
MH  - Progesterone/blood
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 1996/07/01 00:00
MHDA- 1996/07/01 00:01
CRDT- 1996/07/01 00:00
PHST- 1996/07/01 00:00 [pubmed]
PHST- 1996/07/01 00:01 [medline]
PHST- 1996/07/01 00:00 [entrez]
AID - 10.1095/biolreprod55.1.38 [doi]
PST - ppublish
SO  - Biol Reprod. 1996 Jul;55(1):38-46. doi: 10.1095/biolreprod55.1.38.