Document Detail

Progesterone inhibits human infragenicular arterial smooth muscle cell proliferation induced by high glucose and insulin concentrations.
MedLine Citation:
PMID:  12368746     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Diabetes mellitus is a significant risk factor for atherosclerotic peripheral vascular disease. Hyperglycemia and hyperinsulinemia, as encountered in patients with type II diabetes, have been shown to stimulate vascular smooth muscle cell (VSMC) proliferation, a paramount feature in atherosclerosis. Female sex hormones, such as estrogen, have been suggested to inhibit VSMC proliferation. However, the role of progesterone, particularly in patients with diabetes mellitus, has not been examined. Therefore, we studied the effect of progesterone on VSMCs exposed to various concentrations of glucose and insulin.
METHODS: Human infragenicular VSMCs isolated from the tibial arteries of five male patients with diabetes undergoing lower extremity amputation were used. Immunocytochemical studies with confocal microscopy were performed for progesterone receptor identification in these VSMCs. Cells were grown to subconfluence, followed by exposure to deprived media with various glucose (100 and 200 mg/dL) and insulin (no insulin and 100 ng/mL) concentrations. Cells were then additionally exposed to physiologic progesterone (10 ng/mL, progesterone group) and compared with a no-progesterone group. Cell count and methyl-(3)H-thymidine incorporation were used to determine cellular proliferation. Cell count with hemocytometry was performed on day 6. DNA synthesis as reflected through methyl-(3)H-thymidine incorporation was measured at 24 hours.
RESULTS: Immunocytochemical studies with confocal microscopy showed cytosolic progesterone receptors. The no-progesterone group showed a significant rise in cell count (P <.05) at all concentrations of glucose or insulin compared with the control group containing 100 mg/dL glucose concentration. The no-progesterone group also showed a significant rise in thymidine incorporation (P <.05) in the 100 mg/dL glucose-100 ng/mL insulin group and the 200 mg/dL glucose-100 ng/mL insulin group compared with the 100 mg/dL glucose group. In the cell count studies, progesterone significantly inhibited cellular proliferation in several settings. All cell groups cultured with insulin or an elevated glucose concentration showed a significant (P <.05) antiproliferative effect when exposed to progesterone. With thymidine incorporation, progesterone showed a similar antiproliferative effect in cells stimulated with glucose or insulin.
CONCLUSION: Significant reductions in cell proliferation as determined with both cell count and thymidine incorporation suggest that progesterone is an inhibitor of VSMC proliferation induced by our in vitro models of hyperglycemia and hyperinsulinemia. Therefore, progesterone may have a protective role against the atherosclerotic changes associated with type II diabetes.
Brennan J Carmody; Subodh Arora; Matthew C Wakefield; Michael Weber; Charles J Fox; Anton N Sidawy
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of vascular surgery     Volume:  36     ISSN:  0741-5214     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-10-07     Completed Date:  2002-11-04     Revised Date:  2012-10-03    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  833-8     Citation Subset:  IM    
Department of Surgery, Veterans Affairs Medical Center, Walter Reed Army Medical Center, USA.
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MeSH Terms
Arteriosclerosis / etiology*
Diabetes Complications*
Dose-Response Relationship, Drug
Glucose / administration & dosage*,  pharmacology*
Hypoglycemic Agents / administration & dosage*,  pharmacology*
Insulin / administration & dosage*,  pharmacology*
Muscle, Smooth, Vascular / drug effects*
Progesterone / pharmacology*
Receptors, Progesterone / analysis,  drug effects
Sex Factors
Tibial Arteries / drug effects
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Insulin; 0/Receptors, Progesterone; 50-99-7/Glucose; 57-83-0/Progesterone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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